Medicinal Plants in Australia Volume 4

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Flower of the Blackbean, Castanospermum australe. (Courtesy Tony J Young)

MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary





Cheryll J Williams

ROSENBERG

First published in Australia in 2013 by Rosenberg Publishing Pty Ltd PO Box 6125, Dural Delivery Centre NSW 2158 Phone: 61 2 9654 1502 Fax: 61 2 9654 1338 Email: [email protected] Web: www.rosenbergpub.com.au Copyright © Cheryll J. Williams 2013 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher in writing. National Library of Australia Cataloguing-in-Publication data: Author: Williams, Cheryll. Title: Medicinal plants : an antipodean apothecary / Cheryll J. Williams. Print ISBN: 9781922013507 (hbk) Epdf ISBN: 9781925078084 Series: Medicinal plants in Australia ; v. 4 Notes: Includes bibliographical references and index. Subjects: Medicinal plants--Australia. Materia medica, Vegetable--Australia. Dewey Number:

615.321

Printed in China by Everbest Printing Co Limited

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Contents Foreword: Brendan Lepschi  7 Introduction: Re-evaluating the Past – Herbs for the Future  8 1 Flowers of the Materia Medica   18 A Potent Floral Pharmacy   19 Opium Extraction  22 Cardioactive Herbs  24 The Medicinal Rose   29 The Aromatic Rose  31 Remedies from Rosehips   32 Multipurpose Rose Remedies  35 Fragrance and Flavourings in Pharmacy   40 Table 1.1 Overview of the main essential oil yielding herbs and spices with flavouring qualities that are utilised in pharmacy  42 2 Asteraceae: Daisies of the Apothecary  47 The Garden Apothecary  47 A Wound-wort of Distinction: Bellis perennis   48 Analgesic Daisies  51 Table 2.1 Summary of investigations into ‘daisy’ herbs of medicinal value from the genera Acmella, Spilanthes and Wedelia   55 Beach Sunflowers and Singapore Daisies   59 Classic Chamomile   66 A Complex Essential Oil   70 Dandelion: a Famed Liver Tonic   70 A Traditional Anticancer Herb  74 Marigolds: Treasure in the Garden   77 Tagetes: American Marigolds   83 Stinking Roger: an Insecticidal Import   86 3 Validating Bush Medicines   90 Native Antibacterials  91 Pterocaulon: A Fragrant Wound Remedy  96 Plectranthus: Aromatic ‘Native Mints’   98 Table 3.1 Summary of traditional uses of medicinal Plectranthus   101 Antifungal Plectranthus  103 Sneezeweeds   105 Headache Vines  110 An Aromatic Irritant: Tickweed (Cleome viscosa)  114 A Forgotten Herb: the Medicinal Pigweed  118 Buckthorn: a Native Source of Aesculin  123 A Renewed Interest in Native Flora  131 Table 3.2 Overview of Australian plants examined for biological properties in recent scientific literature that are of interest for medicinal purposes  132

4 New Roles for Old Remedies  137 Centella: Ancient Remedy for the Modern World  137 A Remarkable Therapeutic Repertoire   138 Circulatory and Cardiovascular Support   141 A Neuroprotective Agent  144 Table 4.1 Summary of recent investigations of Centella asiatica and its active components   147 Remedies for Recollection  150 Leprosy: Disease and Disfigurement  152 The Leprous Affliction  156  Leprosy Treatment 159 The Legendary Chaulmoogra  161 Achariaceae in Northern Australia  166   Cyanide in Pangium 168 New Roles for Chaulmoogra Oil?   169 Hydnocarpus: Flavonoids of Pharmacological Value 171 Herbal Drugs with Activity Against Mycobacteria   175 Australian Antimycobacterial Candidates 180 Table 4.2 Plants with antimycobacterial potential that are found in Australia (native or naturalised), and closely related native species  184   5 Earth Medicine: A Mineral Pharmacy  193 Antibiotics: The Dirt on Microorganisms  195 Antibacterial Earth   202 Antibacterial Metals  205 Earth as a Poison Antidote  211 Clay for Enterotoxins  214 A Dietary Detoxicant?  219 Drug–Clay Interactions  225 Table 5.1 Summary of clay types used in pharmacy and drug delivery systems  226 Contaminant Considerations   229 Soil Science: A New Look at Urban Earth   237 A Purification Effect   238 Into the Unknown: Microbes for the Future  243 6 A Desire for Dirt?  245 Ancient Art in an Ancient Landscape  245 Ornamentation and Display  246 Mines from Prehistory  251 Ancient Earth   253 Medicinal Muds  255 Mineral Spas   257 Dirt in the Diet? 261 Mineral Matters   264 Table 6.1 White Clay and termitaria samples from the Northern Territory  266 Table 6.2 Summary of Australian clay resources

utilised by Aboriginal people   266 The Downside of Clay Ingestion   269 Parasites from Poo  275 Bugs, Bacteria and the Immune System  278 A Parasite that Influences Behaviour?  283 Medicinal Mycobacteria  285 Therapeutic Earthworms   286 7 Arid Landscapes: Medicinals and Aromatics from the Desert  291 Boobialla Bush Tucker  293 Bastard Sandalwood: Fragrance from the Desert Termite Mounds: Underpinning Ecosystems  277 Precious Resources   306 A Poisonous Mystery   309 Desert Herbals   312 Table 7.1 Summary of the medicinal uses of Eremophila   313 Eremophila longifolia: A Variable Essential Oil  320 A Focus on Antimicrobials   321 Verbascoside: A Versatile Pharmacological Agent   325 Tribe Myoporeae: Intriguing Chemical Complexity  327  Table 7.2 A brief summary of the major chemical components in the Myoporaceae  327 Eeremophilanes from the Asteraceae  329 Dodonaea: A Rather Remarkable Continental Pioneer 331 Table 7.3 Medicinal use of the Dodonaea genus: antimicrobial and healing properties  334 Table 7.4 Additional medicinal uses of the Dodonaea genus   335 8 Ancient Drugs in a Modern World   340 Sorcerous Solanaceae   342 Medicinal Solanaceae   345 The Black Henbane (Hyoscamus niger)  348 Stramonium in Australia  349 Old Herbs for New Drugs  355 Table 8.1 Solanaceae herbs utilised as medicinal plants or for drug production   355 A Modern Market   358 Physostigmine: From Poison to Invaluable Medicine 360 The Infamous ‘Ordeal Bean of Old Calabar’   361 Discovery of a Miracle Drug   362 Drugs for Memory and Warfare   364 9 Pituri: A Mysterious Narcotic  369 An Outback Drug Plant   372 Pituri: Trade Across a Continent   373 The Problem of Identification  374 The Poison Puzzle  375 Discovery of a Mydriatic and Intoxicant  383 Duboisine or Atropine: the Commercial Market   386 Alkaloid Conundrums   388 A Native Drug for the War Effort   393

The Puzzle of Chemical Variation   395 Table 9.1 Duboisia species and the main chemical constituents of pharmacological interest   398 Table 9.2 Australian Solanaceae and their alkaloidal constituents   399 A Toxic Harvest   400 Success … and Failure: The Australian Experience  400 A Matter of Overseas Development  401 10 Tobacco Tales  403 Wild Tobacco   403 Table 10.1 Australian Nicotiana: distribution, use and chemistry  407 Tobacco as Medicine  408 Risky Business   414 Table 10.2 Summary of the Symptoms of Nicotinic Acid Poisoning  416 A Local Tobacco Trade  418 Native Campanulaceae   422 11 Steroids from Yams  432 Dioscorea: Steroidal Substances  432 A Wild Harvest Table 11.1 The Dioscorea genus as a source of diosgenin and herbal medicines  434 Folk Healing Traditions Table 11.2 Traditional medicinal uses of Dioscorea yams  437 Natural Anticholesterol Agents?   440 Anticancer Yams   444 Alternative Steroid Resources   447 12 K  angaroo Apples and Blackberry Nightshades   451 Solasodine for Steroid Production   452 Australian Kangaroo Apples  454 Table 12.1 Summary of Important Medicinal and Toxic Glycoalkaloids in Common Solanaceae   455 The Feral Devil’s Fig  458 The Blackberry Nightshades   462 Table 12.2 Summary of the medicinal uses of Solanum nigrum in different cultures   466 Neurological Influences  469 Anticancer Solanaceae  472 White Nightshade   474 Table 12.3 Traditional Chinese medicine anticancer preparations utilising Solanum nigrum   475 A Curative Anticancer Cream  475 More Medicinal Solanum  481 Table 12.4 Research into additional medicinal uses of the Solanum genus  482 Cestrum, Calcium and Vitamin D  487 Resources   491 Index  541

Foreword As botanists working in a national scientific research institution, my colleagues and I receive many queries from the general public. One of the most frequent areas of enquiry relates to the uses of Australian plants by humans, either for ornament, food or, more significantly, their toxic or medicinal qualities. The last subject has always been a difficult one to respond to, due to the dearth of recent, reliable information. Information on the medicinal properties of Australian plants does exist, but it is widely scattered throughout the scientific and popular literature and as such is not readily available. At least that was the case, until Cheryll Williams embarked upon her ambitious and impressive series, Medicinal Plants in Australia. I first became aware of Cheryll and her work in 2008, when I received an enquiry from her regarding scientific name changes in the Myrtaceae. Thankfully this is an area in which I have some expertise (as opposed to medicinal plants, of which I am largely ignorant), and I was able to help. I also referred her to the Australian Plant Census (APC), a national, collaborative project managed on behalf of the Australian taxonomic botany community by my home institution, the Australian National Herbarium. There began a fruitful and enjoyable relationship; I was impressed and pleased that Cheryll went to such effort to ensure accuracy in a subject (plant taxonomy and nomenclature) that many authors seem content to ignore. As Cheryll mentioned in the first volume of Medicinal Plants in Australia: ‘It [plant taxonomy and nomenclature] is an extraordinarily complex subject … and can drive one to distraction’. I may not always have been able to answer her queries with absolute certainty, the fluid nature of taxonomy and differing opinions negating a definitive answer in some cases; nonetheless, for the most part I like to think I have helped prevent Cheryll from sliding into complete despair and despondency when wrestling with the concepts I and my fellow taxonomists are responsible for generating. When the first volume appeared, I was amazed at the scope and depth of the information presented. My knowledge of medicinal plants is limited at best, and I had no idea of the number of species in the Australian flora which have known or suspected medicinal properties. I had initially thought that Cheryll was intending to publish a single, stand-alone volume, but I

soon realised that there was far, far more to this subject than I had imagined. Cheryll’s careful research and collation of this otherwise scattered information makes for authoritative and entertaining reading. There is the danger that such works may lean too far towards a popular interpretation and sacrifice accuracy for readability, or alternatively tend towards overt and unnecessary detail. Medicinal Plants in Australia is neither of these. The information presented is clear, concise and (most importantly) reliable, referenced as it is to the large scientific literature on this subject and interpreted by someone who is an authority in the field. Through regular email exchanges, I also became aware of the enormous amount of effort required to see each subsequent volume through to fruition and I found myself keenly anticipating the arrival of each new volume. However, in my case it was more a matter of pleasant satisfaction at seeing the finished work, as opposed to exhausted relief at having completed another huge undertaking! Even when struggling under the weight of proofreading, chasing obscure references or interpreting my responses to her queries(!), Cheryll manages an enviably cheerful outlook. I always look forward to the snippets of news from her north Queensland home that often accompany a query or an update on the status of the next volume: newly hatched cassowary chicks in the backyard, three metres of rain falling in five minutes, flying foxes on the back verandah, all things quite foreign to someone in cool, dry Canberra!

Medicinal Plants in Australia is a work that sits prominently in the libraries of both the Australian National Herbarium and the Australian National Botanic Gardens here in Canberra; no doubt it has also found a place in many other libraries in Australia and overseas, as well as on the shelves of anyone interested in Australian plants. It is a work that speaks of the drive, determination and passionate interest of its author, and one that I am very pleased to have been involved with in some small way. Brendan Lepschi Curator, Australian National Herbarium Canberra, 2013

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Introduction

Re-evaluating the Past – Herbs for the Future We live in a world where technological advancement reigns supreme – each day bringing tidings of great strides in the scientific world and quite remarkable innovative technologies. Yet, such innovations are not the mainstay of herbal medicine – and perhaps this is rightly so, for the knowledge that underpins this profession is many centuries old and based on an irreplaceable wealth of clinical experience. This does not preclude the profession from enjoying the benefits that new technologies bring – innovative advances have been made in the extraction, purification and maintenance of the integrity of herbal medicines. Indeed, today we have the choice of a wealth of

remedies, the access to which was once quite restricted. Yet there is the challenge of maintaining the integrity of the knowledge that has been handed down, and to build wisely upon the traditions bequeathed to us from the past. It is a journey that is full of surprises, not because of what we leave behind – but because so many of these old traditions are being validated. In the 1900s, great advances in chemical science were accompanied by some less-than-complimentary views regarding the value of plant-based medicinal products. Strangely enough, this is no less true today. This was reflected in a lack of appreciation of Australia’s floral resources – an attitude that, until relatively recently, endured in many scientific circles. A love of science and innovation leaves many with the desire to seek brighter horizons, with a seemingly old, outdated past relegated to the vaults of disinterest. This perception, unfortunately, leaves many with a lack of appreciation of the great achievements upon which our world is built. In the late 1800s Sir Joseph Hooker made a rather cynical comment about the future of herbal medicine in his introductory essay on the Flora of Australia (then appended to the Flora of Tasmania): I have not alluded to pharmaceutical plants: such may exist, and multitudes of the weeds, seeds and roots of Australia will no doubt enjoy a more or less substantial reputation as drugs for a period, and then be consigned to oblivion. This is the pharmaceutical history of the plants of all countries that have long been inhabited by civilised man, and Australia will form no exception to them, the fact being that of the multitude of names of plants that appear in Pharmacopoeias, the number of really active and useful plants is extremely small.

Red Rock Heart (original artwork courtesy Peter Brooke). In this volume we get to glimpse the greater continental landscape upon which the floral images of discovery are painted. They were not only found in the coastal fringes or the tropical northern jungles. Those searching for medicinal plants trekked across inhospitable territories far inland – a great adventure that resulted in some rather dramatic discoveries that were to rival some indispensable European drugs of the time. 8

Re-evaluating the Past – Herbs for the Future

This perspective was fairly widespread – a sceptical belief that persisted throughout the twentieth century. Sir Joseph was incorrect on a couple of counts. Firstly, there are cultures with successful traditional medicine systems that have evolved a high degree of clinical competency in herbal therapies. Traditional Chinese and Indian Ayurvedic medicine are among the most successful of these, with an excellent reputation for efficacy. There are many other respected traditions that continue to be practiced – Indonesian Jamu, Japanese Kampo, Thai and Korean traditional medicines. An intriguing testament to their validity is the fact that modern drug companies have acquired numerous pharmacological ‘leads’ from these traditional pharmacopoeias. Everyday, a vast variety of herbs continue to be investigated with the ultimate aim of producing new drugs. Secondly, the range of useful plant-based chemicals is extremely diverse. The evaluation of their pharmacological activity continues to inspire numerous discoveries every year. A remarkable diversity of journals, which are devoted to these chemical discoveries, readily attest to this. On the other hand, Hooker’s observations on the lack of interest regarding the development of medicinal plants in clinical practice was, unfortunately, all too accurate. The discovery of antibiotics and synthetic chemistry in the early to mid 1900s led many to blindly invest their faith in the new ‘magic bullet’ era of pharmaceuticals that had arrived. Only much later would the unhappy consequences of the prolonged use of many of these drugs become apparent – and their detrimental side-effects truly become appreciated. The evolution of drug-resistant strains of microbes presents an even more worrying problem for the future. It is these areas of concern regarding drug safety that has led to a greater willingness to support herbal medicine traditions. Almost a century after Hooker published his criticism, the words of the distinguished American Professor Norman Farnsworth illustrate a far different perspective on plant-based medicinals. The low incidence of toxic reactions was deemed worthy of particular comment: There are many proponents of traditional medicine who maintain that the use of decoctions, infusions and/or Galenical preparations of botanicals is the most highly developed form of drug-taking that is desirable or

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necessary. In many instances I am inclined to support this opinion. It is clear to practically everyone what the consequences of continued use of synthetic drugs (including purified natural products of known structure) are, in the way of producing undesirable and/or toxic effects. In the United States, as well as elsewhere, there is a growing sentiment in favour of a return to the use of effective crude botanicals for the treatment of some diseases. Much of this sentiment arises out of knowledge that, at least in the United States, synthetic drugs lead to iatrogenic disease. This has cost the American public about $2 billion annually in additional health care funding. An average hospital stay is increased by 3–5 days owing to these drug-induced side-effects. Although it is difficult to acquire hard data relative to documentation of the incidence of adverse effects due to Galenical forms of medicinal plants (indeed, such data may not exist), it is generally felt by most persons knowledgeable in the use of traditional medicine that side-effects are rarely encountered (Farnsworth 1980).

This was written around three decades ago – and little has changed. Despite remarkable advances in diagnostic tests, scanning technology and drug delivery systems, the medical system crumbles from within. In many places the incidence of iatrogenic disease has risen, the quality of patient care diminished, and continued crises occur with regard to hospital waiting lists and emergency care. Indeed, the basic practice of medicine has come to rely on the provision of drugs as its mainstay – and many physicians have little time to address other factors leading to the ills that plague us, particularly poor lifestyle options and emotional distress. One cannot belittle the beneficial drugs that have resulted from chemical discoveries, nor can it be implied that synthetic developments all exhibit undesirable side effects. However, it is an accepted fact that drug toxicity is a very real part of modern medical practice. It therefore becomes important to realise that these drugs are not the only treatment option available. This is an extremely valid proposition that needs to be given a lot more support in orthodox circles. Many plant-based preparations not only retain their therapeutic validity – investigations continue to expand the knowledge of their benefits, particularly in the area of preventive medicine. However, there are a number of pervasive contradictory perceptions that surround the use of herbal remedies:

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

• They are all ‘old folk tales’ and therefore ineffective. • Herbal remedies are innocuous and their use is little more than ‘faith healing’. • Herbal remedies are dangerous, for one reason or another. Yet the past history of drug development is full of ‘old folk tales’ that have resulted in exceptionally effective medicines – some of which continue in use, in one form or another, to this day. In addition, a reliance on potent, sometimes poisonous, plants has certainly been the mainstay of medical practice since time immemorial – and this avenue of investigation continues to be actively researched in the hope of developing new drugs. The cardiotonic drug digitalis from Foxglove herb (Digitalis purpurea), the antihypertensive agent reserpine from the Indian Snakeroot (Rauvolfia serpentina), the anticancer drugs vincristine and vinblastine from the Madagascar Periwinkle (Catharanthus roseus) and taxol from the Pacific Yew (Taxus baccata) are probably the classic examples of successful drug developments – although there are many more natural product discoveries that lie unappreciated. Antifungal, antibiotic and anticancer agents from microbial sources would be among the most prominent. Indeed, 40 per cent of prescription drugs continue to be based on natural products, as are 49 per cent of the new chemical products registered by the American FDA. In the decade between 1983– 1994 around 60 per cent of approved new drugs (including those in anticancer clinical trials) and 78 per cent of new antibacterial agents were natural product-based. Indeed, these resources have been the traditional source of ‘pathfinder compounds’ – the diversity of which continues to be unrivalled by any chemical database in existence (Strobel & Daisy 2003). In some western countries, herbal medicines have progressively acquired a more vital therapeutic role – particularly for those wishing to take more responsibility for their own health. These remedies, in many cases, have already proven to be of inestimable worth in clinical situations. As toxic plants have been largely discarded from the herbalists’ repertoire, the majority of traditional herbal medicines have an excellent track record of use. Because so little is known about these remedies by orthodox medicine, those concerned about drug interactions tend to try

and exclude herbs from the therapeutic equation – often laying the blame for a drug interaction with a herbal medicine and, subsequently, the opportunity for a bit of scaremongering sometimes arises. Which, to be quite honest, seems strangely illogical given the fact that people who are trying to be responsible for their own health care are exactly what the medical profession and the regulatory authorities need. Many forget that it is the drug treatment that is usually the foreign component in the equation.

Aconite (also known as Wolfsbane or Monkshood, Aconitum napellus) is one of the toxic ornamental herbs prized for its wonderful blue flowers. Joseph Maiden mentioned: ‘There is a large demand for the dried root for the preparation of aconite liniment and tincture. The root is very poisonous, and intending growers must be warned not to mistake it for horse-radish’ (Maiden 1892). While its toxic reputation ensured that Aconite was only utilised externally in European traditions, it was valued for centuries in China as an anti-arthritic herbal medicine. This was due to the development of a detoxification process that significantly modified the poisonous qualities of the drug (see Chapter 5 for further details). Aconite was later developed as a valuable homoeopathic remedy that was recommended for the treatment of fevers and inflammation – and emotional disorders characterised by fear.

Re-evaluating the Past – Herbs for the Future

The chemical complexity of a herb is exceptionally hard to define – and, while we often appreciate the fact that a number of main components are responsible for a remedy’s activity, the entire picture can be elusive. This is not necessarily a problem in herbal medicine, which is based on quality extraction processes that utilise the whole herb – not a single chemical component. The latter is more appropriate for drug development purposes, hence the proliferation of literature emphasising the discovery of new chemical components. While this type of analysis does provide valuable insights into why a plant works, all too often it only hints at the remarkable chemistry that nature has provided. An appreciation of the multifaceted character of a plant remedy is integral to the practice of herbal medicine. There is a need for a change of attitude that supports tried and tested remedies with a good clinical history. There is enormous scope, particularly for immune supportive herbs. There are liver and kidney detoxicants that can mediate drug side-effects, and a range of antidiabetic agents with effective blood sugar regulation attributes. These can often act as a complement to drug therapy and prevent long-term complications. The scope is quite extraordinary and this work provides numerous illustrations with significant future value. It is, in many ways, unfortunate that analytical chemical developments allowed a ‘new’ drug-based form of medicine to replace the old herbal traditions in such an all-encompassing manner. As a result, the knowledge of many remedies from native Aboriginal lore, as well as from traditional European sources, faded over time. In particular, in the 1940s, the perception that there was simply no need for many of the old remedies with the advent of antibiotics became prevalent – even though, at that time, the phenomena of drug-resistant bacteria and individuals who were allergic to penicillin had already been made manifest. Those with an interest in our floral heritage may mourn the loss of so much knowledge, yet we are lucky that the art of herbal medicine, enshrined in the teachings of traditional practitioners, survived at all. The importance of this for mainstream medicine is also little appreciated – for had we lost this vast repository of practical herbal knowledge our scientific world would be bereft of much of its inspiration today. Yet another threat looms. This comes from a

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lack of appreciation by those who are not clinicians with regard to the complicated process of diagnosis and treatment. It is easy to do ‘test tube chemistry’ – but the reality of clinical practice is far different. Experience cannot be replaced by lessons in biochemistry, physiology and drug management, or by bestowing qualifications that ignore the essential need for practical skills based on clinical care. Even the language of modern medicine tends to dehumanise the clinical symptom picture, leaving little appreciation of the suffering and stress associated with many conditions. The problem also lies in the fact that clinicians are not researchers, nor do they usually have the time, resources or finances to undertake such a role. Overall, there are too few of their reports in the literature – and in this way we continually lose an extraordinary amount of irreplaceable knowledge with regard to the properties, mode of preparation and practical use of herbal medicines. Those who would evaluate the literature often fail to acknowledge the vast experience of practitioners in the field. As a result research papers are published that have little true appreciation of the complexity that is inherent in treatment protocols.   The addition of an unsympathetic, and often uninformed, bureaucracy to the equation does little to inspire confidence in a fair appraisal of the art of herbal medicine.1 In my own case, I have had proprietary homoeopathic medicines confiscated because they contained yohimbine and I did not have the appropriate permit – even though, as homoeopathics, they were not strictly illegal. However, I was advised that to organise the paperwork would take too long (over ten days) and I risked being fined. It was simply not worth the effort and the goods were destroyed. On another occasion I had sent medicines from Papua New Guinea (where I was residing at the time) to family in Australia. These were confiscated by Customs – even though they had been originally purchased and manufactured in Australia. 1 Indeed, a recent bright bureaucratic idea involved a restrictive ban on plants that contained chemical compounds which could be considered to have potential as illicit ‘drug plants’. The fact that many ornamental plants, a fair number of native species, and quite a few weeds, could fit in this category could easily have criminalised all walks of life – ranging from plant nurseries, botanic gardens and plant collectors, to backyard gardeners. Needless to say, the legislation was variously described as ‘insane’, ‘idiotic’ and ‘insulting’. Assurances that the legislation was only designed to target the illegal drug market were met with a great deal of scepticism (see Kirk 2012).

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Ephedrine: An Invaluable Discovery

Ephedra major subsp. procera. Ephedra plants are fairly unassuming shrubby herbs or small shrubs with twiggy stems. Numerous species contain alkaloids, primarily ephedrine and pseudoephedrine. Official sources are the Chinese species Ephedra sinica, E. distachya and E. equisetina – although species from other countries, such as E. major and E. intermedia, can provide alternative resources.

Ma Huang has an extremely ancient history, with records dated around 3100 BC (some 5,000 years ago) mentioning its use. This remedy was destined to make invaluable contributions to medical science after the discovery of ephedrine from Ephedra sinica in the 1920s by the pharmacologist Ku Kuei Chen.   As with many of the truly famous plantderived drugs the herb itself was not destined to achieve notable pharmaceutical fame – it was the chemical ephedrine, which had effects similar to adrenaline, that quickly became approved for use by the American Medical Association in 1926. Importantly, its significant decongestant and antispasmodic effects were suitable for commercial exploitation by drug companies. For the better part of a century this discovery has provided inspiration for pharmaceutical drug derivatives that have earned the industry billions of dollars in revenue – yet few have acknowledged the great value of this humble herb. Indeed, in Australia, its use is banned to the very profession that traditionally deployed the herb for centuries. The term Ma Huang refers to the herb as used in Chinese medicine; it should not be applied to the extracted alkaloids or their various combinations. The integrity of the herbal product relies on the species which is utilised, as well as processing methods and storage conditions. Certainly, the use of the herb is not equivalent to the deployment of specific alkaloids – and the two should not be confused. While the traditional use of the remedy has not generally been associated with toxic reactions, the reputation of the herb suffered when commercial products containing Ephedra were inappropriately formulated and marketed. Particularly worrying was the fact that the isolated alkaloids (ephedrine, norepinephrine) were utilised instead of the herb – a substitution that seriously increased the likelihood of toxicity. It is little appreciated that the pharmacology of Ma Huang is somewhat different from pure ephedrine. Other constituents in the plant (probably flavonoids) interfere with the absorption of alkaloids from the gastrointestinal tract, and this slows down their effect in the body. Compounds are also present that have

Re-evaluating the Past – Herbs for the Future

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competing actions. For example while the root extract acts as a hypotensive agent, it also contains a hypertensive alkaloid (maokinine). The shoot extract likewise showed a hypertensive action, although there a number of compounds (ephedradines) in the plant which are hypotensive (Izaddoost & Robinson 1987).   Traditionally, the mode of preparation is extremely influential and the herbal effect can vary greatly, depending on the processing used. The twigs or stems are employed raw as a diaphoretic, or baked with honey to elicit an anti-asthmatic action. In contrast, the root is a highly effective antihidrotic (acting to stop sweating in fevers, etc). Therefore, for herbal medicine purposes, it is important to evaluate the clinical use of plantbased remedies, rather than the effects of the isolated principles.

 This work tries to marry the old with the new – the debt that new remedies have to old inspirations, and recent innovative applications for age-old herbs. It begins with an emphasis on how important the conventional cottage garden was as a medicinal resource. It was not merely a place for ornamental curiosities, or for the production herbs and spices of culinary value. Numerous medicinal plants were readily cultivated in the early days of European settlement in Australia. While wound-healing herbs for treating infections and fractures predominated, some surprisingly effective remedies for dropsy and heart problems could be found in just about every major garden planting. Some were highly ornamental, a few were nondescript, and others were so common they were simply taken for granted. The important point to remember is that many herbs gained official recognition of their usefulness, much of which has endured to today. Indeed, in some cases research has not only validated their efficacy, it has given these remedies ‘a new life’ in modern therapies. Even so, we need to appreciate the wisdom of the ancient texts and traditions – and there is a surprising level of continuity. Many old herbal texts have provided invaluable drug inspiration –

Ornamental urn advertising the Pure Drugs that were dispensed in Australian apothecaries (EJ Martin’s Chemist, Herberton Historical Village, north Queensland).

Nineteenth-century medicine chest ca.1880 held in the Townsville Museum. (Courtesy Townsville Museum)

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

A Walk in Ochre Country (original artwork courtesy Peter Brooke). Medicines can come from some unusual sources. Indeed, ochre has an ancient history of practical, medicinal and artistic use across the world. Mined in Australia since ancient times, its use often holds great cultural significance for Aboriginal people. Coloured ochres have been integral to the execution of historical and modern artworks – as well as possessing significant healing properties with some rather surprising applications.

irreplaceable repositories of a practical wisdom that is not widely appreciated today. There are some fascinating records. Incidents of microbial contamination have resulted in the serendipitous use of antibiotic remedies since ancient Egyptian times. Even beer and bread recipes had a beneficial antibacterial component. There are many tales of the medicinal use of mud, moulds and even remedies from worms that, in reality, have a substantial basis in truth. This extends to the Aboriginal use of ochre, breast milk, urine and saliva as adjuncts to therapy. Indeed, medicine has become so far removed from its origins that many forget that antibiotics originated from moulds and soil microbes. To this day, research chemists regularly investigate these resources in the hope of new discoveries – some of which can be quite unexpected. Certainly this has been the case with the revelation that common soil-transmitted helminth infections (hookworm, roundworm) show significant benefits for the immune system, particularly for the prevention of

autoimmune disease, albeit ‘worms in the system’ would normally be considered highly undesirable.   Even the rather odd habit of eating earth has its pros – and cons. The latter can sometimes be linked to environmental issues, with lead and arsenic being foremost among the toxic soil contaminants that have a significant impact on health issues. For better or worse, the use of diverse chemicals has had (and continues to have) an irreversible impact on the world in which we live. Be prepared to be surprised at just how well modern techniques are verifying age-old traditions, and the ramifications for the Australian flora. There have been a number of natives that became famous as drug plants, stories that have been largely forgotten and relegated to the past. They include the native ‘tobaccos’, steroid resources and raw materials for the contraceptive pill. Hopefully this volume will bring their tales to life, and provide an appreciation of how important native resources truly are – and the indispensable place that many common plants and

Re-evaluating the Past – Herbs for the Future

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Floral Fantasia (original artwork courtesy Lolli Forden, Cairns). Within the vibrant flash of flowers and verdant green foliage, plants retain chemical secrets that may never be truly unravelled by science. There are somewhere between 300,000 and 500,000 different plant species – with merely 15 per cent having been subjected to phytochemical analysis. Even less (6%) have been evaluated pharmacologically. The majority of this analysis has been done on flora of the tropical and subtropical regions, with colder climates remaining largely unexplored –and entire new phytochemical worlds lie hidden within marine environments. The recent discovery of microbial endophytes within plants presents a similar unknown world of potential that may well help explain the medicinal efficacy of many remedies. It is equally surprising to note that, despite the discovery of numerous antibiotics and anticancer agents from microbial sources, only around 1 per cent of the microorganisms visible under a microscope have been cultivated (a necessary part of the identification process) – therefore ‘the microbial universe clearly presents a vast untapped resource for drug discovery’ (Cragg 2012).

‘old folk treatments’ once had as household remedies, and as medicines for the professional apothecary’s practice. There is a lot to appreciate and, as time (and this tome) will show, the ages of discovery, learning and innovation are far from over. Plants are a constant aspect of everyday living that provide an important link between the past and the future. It has been a remarkable tour of discovery into uncharted botanical waters on these antipodean shores. Truly, it is a fascinating story.

Author’s Acknowledgements

Tony Young has been ever reliable with his persistent research efforts, and this volume has been an exceptional undertaking. He deserves many thanks for tracking down numerous hard-to-find images – as well as his painstaking work checking (and rechecking) botanical and chemical names, and

compiling the index. Thanks, also, are due to Shaune Williams and Brigitta Flick for their professional support – and to Anne Savage for her editorial contributions. As always, we have hunted high and low for many of the images that make these volumes such a visual feast – and many thanks are due to David and Scilla Rosenberg for being so patient with the enormous workload involved in such an endeavour. We try our best to contact the authors of any images utilised, even if they are under free-licence, to ensure we have the correct acknowledgements and to express our appreciation of their wonderful efforts. In the main we have been successful, but there are, regrettably, always a few who ‘slip though the net’. We would also like to express appreciation of the exceptional resource that Wikipedia and Wikimedia Commons have become, along with totallyfreeimages. com, and the remarkable contributions they contain. Once again, the efforts of Peter Woodard, Brian Walters and the Australian Native Plants Society (ANPS) have been invaluable. The lovely images of native flora by Craig Nieminski and Russell Cumming also feature in a number of chapters – as do various

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

drug plants by Farmer Dodds. In the section on Emu bushes (genus Eremophila, Chapter 7), there are some outstanding contributions by Melburnian that rate special mention. Equally inspirational are the unique artworks of Peter Brooke and Lolli Forden. In addition, access to geological images, courtesy of Mark A Wilson and Rob Lavinsky, were essential for the sections dealing with minerological matters. The botanical expertise of Brendan Lepschi (Australian National Herbarium) has maintained an essential role in ensuring the botanical integrity of much of this work. While a few companies such as Martin & Pleasance, Cathay Herbal and Acuneeds were very generous in their assistance with product images, it was quite puzzling to find that quite a number of Australian companies producing nutritional and herbal medicines declined. Thank you also to the Herberton Historical Village (Atherton Tablelands, north Queensland) for their gracious access to a treasure trove of old herbal and drug paraphernalia – and to The Apothecary of Cairns. On a personal level, mention should be made of the support given by Helen Timmins, Heather Rabbich, Kathryn Collis, Chris Crosland, Jenny Sheppard, Sue Jordan, Bruce Allen, Margaret Young, Joan O’Grady – and my deepest gratitude to the exceptional Dr Sue Cory.

A Perfect Posy (original artwork courtesy Lolli Forden, Cairns). Many common flowering plants have an enduring healing reputation resulting from their medicinal use for millennia. Even today, new research with regard to old remedies is opening a world of therapeutic surprises that continue to validate and enhance their future as medicinal plants.

Continued support by Brigitta Flick and Tony Young for Daintree Wildlife Rescue has seen us successfully struggle through yet another difficult year. Kim and Forest Starr from Hawaii have continued to be unstintingly generous with unrestricted access to their extraordinary image repository.

Re-evaluating the Past – Herbs for the Future

Erosion: A stark reminder of the consequences of poor environmental management (original artwork courtesy Peter Brooke).

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Chapter 1

FLOWERS OF THE MATERIA MEDICA

This medicine chest has an interesting history. It was originally employed at the London chemist and druggist Thomas Keating & Co, St Paul’s Church Yard, London, 1830–45. Captain Robert Bailey, of the steamship Tartar, acquired it for his voyages carrying Australian wool to England – and later passed it on to relatives in the Dean family, who lived on a farm outside Gulgong, New South Wales. Subsequently, the chest was given to the local pharmacist, Mr DH Dugan – who had it on display in his pharmacy. His son donated the chest to the Powerhouse Museum, Sydney. (Image courtesy Powerhouse Museum)

Until the last century or so, the skilled medical practitioner required a good level of botanical knowledge. Following this tradition, the physicians who initially came to Australian shores brought their own supplies. They were usually intelligent, accomplished scientific men, albeit faced with a new land that they knew nothing about. This hampered the

initial search for native remedies that could be pressed into service as substitutes for common European drugs – although the Eucalypts, Tea Trees and various native aromatic herbs made a good impression. Drugs such as belladonna, hyoscyamine and opium had to be imported – or cultivated. While a few survived in propagation, many did not, and a couple escaped into 18

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the wild to prosper and become a perpetual nuisance. Those that simply ran wild included the styptic and antihaemorrhagic remedy Shepherd’s Purse and the anti-asthmatic herb Stramonium. Surprisingly effective remedies could be easily grown in the cottage gardens of the colony – a few were highly ornamental, while others were nondescript. Some were so ubiquitous that they were simply taken for granted. A number provided remedies for dropsy and heart problems, including cardiotonics that were sourced from the delightfully ornamental Foxglove, Lily-of-the-Valley and the Summer and Winter Adonis herbs. Even the Apothecary’s Rose and various poppies would take pride of place in colourful garden displays. With a vast heritage in the utilisation of medicinal plants, the Chinese immigrants later ran their own intriguing pharmacies. Interestingly, they too looked to the native flora to find substitutes where possible and, in many ways, would have had a greater appreciation of its practical therapeutic value than the European community.



A Potent Floral Pharmacy Syrup of Field Poppy

Field Poppy (Papaver rhoeas) is naturalised throughout much of the temperate parts of the Australian content, notably Western Australia (southwest region), South Australia and Tasmania.

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The European Field Poppy (Papaver rhoeas) possesses medicinal attributes, albeit of a minor nature in comparison to its famous relative, the Opium Poppy (P. somniferum). In India the latex from the Field Poppy capsule was considered narcotic and sedative – although it does not contain morphine and the effect is probably due to the presence of other alkaloids, notably rhoeadine. The fresh petals also contain an anthocyanidin (mekocyanin), which is chemically related to the cyanin of red rose petals. They were once a valued colouring agent for wine and pharmaceuticals (Evans 1989). A syrup of Field Poppy petals was officially listed in the 1949 British Pharmaceutical Codex (BPC). Extracts of the petals were considered to have calming, pain-killing, sudorific (sweatpromoting) and mucilaginous properties, hence their use for easing cough and hoarseness. In Turkey the flower syrup provided a tonic for anaemia. Furthermore, the crushed leaves were utilised as a diaphoretic for treating colds and feverish conditions. Some of these effects may be linked to alkaloid components, although one study of an alkaloid-free extract prepared from Field Poppy petals demonstrated sedative activity at a dose of 400 mg/kg (Soulimani 2001). An excellent quality oil, comparable to Olive oil, can also be extracted from the seeds. In the early days of Australian settlement opium was a mainstay of medical practice due to its analgesic and anti-diarrhoeal properties. Laudanum was a common tincture (alcohol-based) opium preparation.1 The formulation originated with a Dr Sydenham of London around 1670. Prior to this, the term ‘laudanum’ had been used to describe the solid opium preparations of the seventeenth century that were official in the early editions of the London Pharmacopoeia. Laudanum tincture, which contained around 10 per cent opium (equivalent to 1% morphine), had the same therapeutic value as opium itself and was widely employed in diarrhoeal and dysenteric disorders. 1 This should not be confused with the resin Ladanum (in some instances mistakenly spelt laudanum) that is sourced from Cistus creticus.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Numerous Laudanum recipes were concocted. They included a Black Drop or Quaker Laudanum, and a Vinegar of Opium that was around three times the strength of ordinary Laudanum. Paregoric (Camphorated Opium Tincture) was a weaker preparation (about 1/25th less in strength than opium tincture: 0.4 mg/mL) in combination with other ingredients such as Anise oil, Benzoic acid and Camphor (Martin & Cook 1956).2 These opium preparations had substantial potential for toxicity, making the dosage extremely important. Simple errors in the amount used, or the type of preparation, could easily result in an overdose. This has occurred with the use of Opium tincture instead of Paregoric – a mistake that increased the opium intake over 25 times that of the regular dose. The risk of addiction due to the widespread use of Laudanum was equally serious. Symptoms of poisoning were associated with various degrees of euphoria, sedation and respiratory depression, leading to respiratory and cardiac collapse and, possibly, death.

Tincture of Opium, British Pharmacopoeia, 1874.

2 ‘Paregoric’ was an ancient term used in writings on pharmacy and medicine. It described an anodyne (mild pain-killing) or soothing preparation generally employed for the treatment of coughs, nausea and abdominal pain.

  Poppies in Australia

The term ‘laudanum’ was coined by Paracelsus to describe a solid type of medicine whose ingredients were a professional secret. (Courtesy Cydone, Wikimedia Commons, Public Domain) Papaver somniferum.

Powdered Opium: prepared by Australian manufacturer Taylors Elliotts & Australian Drug Pty Ltd, Brisbane.

No representatives of the Poppy family (Papaveraceae) are native to Australia – although a number have become naturalised, including the infamous Opium Poppy (Papaver somniferum) which is found throughout New South Wales, Victoria, South Australia and Tasmania. In addition to Papaver somniferum (subsp. somniferum and subsp. setigerum), five other species are listed: Bristle Poppy (P. aculeatum), Pale Poppy (P. argemone), Long-headed Poppy (P. dubium), Rough Poppy (P. hybridum) and the Field Poppy (P. rhoeas).

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  Very early introductions to the continent included Papaver aculeatum, which was even mistaken for a native inhabitant by researchers. Joseph Bancroft wrote of his interest in Papaver horridum (now P. aculeatum): I have for some years past been anxious to ascertain whether the native poppy contained morphine, but it was not until last August that I was enabled, through the kindness of Mr. J. H. Simmonds, to obtain a supply of the plant. All parts of the plant have a slightly bitter acrid taste. An extract is very poisonous to frogs … I endeavoured to prepare morphine from an extract of this plant according to the method prescribed by the British Pharmacopoeia, but failed to get even a trace of that substance, or indeed of any other substance. Judging from this and from the physiological effect on frogs it would appear that the active principle is not morphine. It is, however, quite as poisonous as morphine (Maiden 1889).

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noted: ‘The seeds yield about 50 per cent. of their weight in oil, and for this article alone it would pay to cultivate the plant in the Colony’. He concluded: An acre of well cultivated poppy plants will yield about half a ton of seed, and from this can be expressed 560lb. weight of oil. The residue makes very good feed for cattle. The oil is inodorous [lacking aroma], and of an agreeable flavour, so that it can be used for domestic purposes, such as salads. Besides this it can be used for a great variety of purposes, and is extensively used in house-painting. Mixed with white lead it leaves a beautiful surface, which does not afterwards change by the action of light into a dirty yellow colour. After the crop is gathered cattle and sheep may be turned into the field to eat the stalks down. Although they may not be considered very fattening, still the sheep will eat them, without any ill effects.

The Opium Poppy is easy to grow, and in the late 1800s it was given consideration as a commercial crop in New South Wales. Fred Turner mentioned its potential value in a review of New Commercial Crops in the Agricultural Gazette of New South Wales: According to [the Statistical Register] the importation of opium into the Colony for the year 1889, amounted to 25,256 lb., valued at £47,915, and the exports to 5,068 lb., valued at £10,734, thus leaving the value of home consumption at £37,181. It would take the produce of about 450 acres to supply the annual demands for opium alone in this Colony. An acre of well cultivated poppy plants would yield from 40,000 to 50,000 capsules, and these will exude under proper treatment from 40 lb. to 50 lb. or even more, of opium, the usual market value of which is from 30s [shillings] to 35s per lb. Farmers in this Colony are now cultivating crops which give them smaller returns, and they might do much worse than put under cultivation an acre or two of the opium poppy. It is only by attending to these ‘small creatures’ that farmers can ever hope to make their calling a more lucrative one. Many of these crops can be harvested at slack times, whilst the ordinary crops are maturing. The poppy plant occupies the land but for a few months of the year – usually about 3½ – so that produce can soon be turned into a marketable commodity (Turner 1891).

If this market encountered problems, then there were a number of other options for the use of the plant. Certainly, it was a suitable oil crop resource, as Turner

Decoction of Poppy capsules, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

The dried poppy capsule has similar properties to opium as an anodyne and narcotic agent, albeit much weaker in effect.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Opium Extraction

can be substantial variation in quality. Harvesting too early will yield a watery product, whereas collections that are done too late result in a lower alkaloid level. The slices into the capsule must be shallow, as piercing the capsule will let the latex drain inside and it is not recoverable. Poor processing methods or inadequate storage conditions can easily result in degradation of the morphine content. Heroin bottle, originally contained 5 grams of heroin. Heroin (diacetylmorphine) is an opioid drug synthesised from morphine. (Image courtesy author Mpv_51 via WIKI)

Opium latex from capsule. (Courtesy Farmer Dodds, flickr)

The extraction of opium was never an easy task. Raw opium is largely composed of waxes, resins and a variety of inert ingredients that limit the material available for morphine extraction. Poppy capsules contain very small amounts of morphine, that is, 0.18–0.28 per cent. The time of latex collection is important, with peak production occurring 2–3 weeks after flowering (a few days after the petals fall off). Harvesting any earlier, or later, significantly reduces the yield. After the pod ripens following extraction of the latex, it contains no opium. The ripe seed chemistry is equally innocuous, which makes them suitable for cooking purposes or oil production. The official Opium standard, Opium BP, is standardised at 10 per cent morphine, not less than 2 per cent codeine, and thebaine up to 3 per cent. However there are up to 30 other alkaloids in the plant. The papaverine alkaloids (noscapine, narceine and papaverine) are counted among the minor constituents of interest (Evans 2002). While modern production methods utilise the whole plant for solvent-extraction of the alkaloids, the traditional collection process was based on the harvest of the pod latex. This involved the skilful application of shallow incisions in the immature green pod, which had to avoid puncturing the pod or disturbing the seeds inside. An oddity of nature ensures that there is a limited time availability of the latex from the poppy capsule – around 5–10 days after the petals fall off. This is the only time that the mixture of alkaloids suitable for opium production is available – and there

(Below) Raw opium. (Courtesy Eric Fenderson, Public Domain)

Surprisingly, opium continues to have a place in modern medical practice. The effect of opium, which is slower than that of its major constituent morphine, is indicated for intractable diarrhoea as it slows the intestinal transit time, allowing more effective fluid absorption. Opium also has diaphoretic attributes (induces sweating) and can decrease metabolism. Indeed, the latter resulted in its former use (as well as codeine) for the treatment of diabetes. Codeine has milder analgesic and sedative properties, as well as an antitussive effect, hence its incorporation into

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numerous cough medicines – although there are some potent preparations on the market, and constipation can be a serious side-effect of prolonged use (Evans 2002).

  Wayward Wallabies

Female wallaby and young. (Courtesy Craig Nieminski, flickr)

Medicinal properties of Opium extract, from British Pharmacopoeia, 1934.

Tasmanian poppy crop. (Courtesy Peter Sharman)

Syrup of Poppy, from British Pharmacopoeia, 1874. Poppy capsule-based syrup was once commonly used as an ingredient in cough medicines. However, the alkaloid content was variable with toxic potential that could easily lead to incidents of poisoning in children. Laudanum tincture. Noscapine (narcotine) has antitussive properties, as well as undesirable emetic and nauseant effects. For this reason the compound is removed from tincture preparations, which are known as Denarcotised or Deodorised Tincture of Opium (DTO). This should not be confused with diluted tincture of opium (which should not be abbreviated to DTO), a drug that is utilised for treating opiate withdrawal in newborn babies. (Image courtesy djm55, Wikimedia Commons, Public Domain)

Wallabies in Tasmania have been raiding the local opium poppy crops in times of scarcity – although this does not appear to be motivated by the desire for an opportunistic drug hit. The animals are simply searching for the nutritious seeds within the poppy capsule. However, during their foraging it appears that the wallabies may quite often ingest some poppy alkaloids, although the effect on animals is not the same as the human experience. Maude Grieve (1931) commented: ‘Opium and morphine do not produce in animals the general calmative and hypnotic effects which characterize their use in man, but applied locally, they effectually allay pain and spasm. Owing to the greater excitant action in veterinary patients, the administration of opium does not blunt the perception of pain as effectually as it does in human patients.’ Animal responses to morphine can therefore vary considerably. It has an excitant effect in cats, horses, cattle and swine, and the synthetic codeine-derivative Tramadol is more suited for use as a veterinary analgesic (The MERCK Veterinary Manual, www.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

merckvetmanual.com). The mysterious ‘crop circles’ that have appeared in the poppy fields may therefore be due to wallabies doing a bit of ‘circle hopping’ due to this excitant effect. There are stories of other animals such as sheep and deer behaving in the same manner.

Cardioactive Herbs

Foxglove entry, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

Digitalis tincture. (Courtesy The Apothecary, Cairns)

The lovely Foxglove (Digitalis purpurea), which has long graced cottage gardens, would be considered the most clinically successful of the cardiotonic herbs. While a surprising variety of ornamental herbs have similar cardioactive properties, for various reasons they never achieved the therapeutic success of Foxglove. Although their properties would be little appreciated today, many of these herbs were formerly considered an invaluable part of medical practice.

Foxglove, Digitalis purpurea, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. Foxglove is naturalised in Tasmania – as well as being a garden escapee in New South Wales and Victoria. The cardiotonic properties of Foxglove saw it utilised therapeutically for more than two centuries. Importantly, this elegant herb is the origin of the drug digitalis. Joseph Maiden mentioned that the plant was easily grown as a local crop: ‘The leaves of the Foxglove … are required in both the fresh and dried state. The fresh leaves are used prepare the juice’. In some treatment protocols Adonis (from Adonis species) was alternated with digitalis – possibly because it had cardiac benefits of a different calibre to the latter and, importantly, lacked the cumulative toxicity which could be associated with repeated doses of digitalis. The Summer Adonis or Pheasant’s Eye (Adonis microcarpa, formerly A. annua) favours a temperate climate, particularly South Australia – although it is also present in Western Australia (southwest), New South Wales, and southern Queensland. (Image courtesy Pablo Alberto Salguero Quiles, Wikimedia Commons, CC-by-SA3.0)

FLOWERS OF THE MATERIA MEDICA

25 (Left) Adonis vernalis.

[[PIX [[Ca [[PIX [[Cap

The Climbing Oleander, Strophanthus gratus. This vine, which has become widely planted as an attractive tropical ornamental, is of particular medicinal interest. Although many species of Strophanthus have cardioactive potential, only S. gratus retains practical value. The seed contains 4–8 per cent ouabain (strophanthin-G), a substance unique among the cardiotonic glycosides that can be easily extracted in a crystallised form. Ouabain exhibits a consistent level of activity, against which the potency of similar substances can be accurately compared – hence its adoption as a reliable test standard for the evaluation of cardioactive drugs.

(Below) Adonis vernalis, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

The Summer Adonis (Adonis microcarpa) and the Winter Adonis (A. vernalis) are two examples that contain glycosides (adonitoxin and cymarin, respectively) which act similarly to those of Strophanthus and Digitalis.3 The Martindale Extra Pharmacopoeia of 1952 provides the following details: ‘Adonis had a digitalis-like action. It slows the heart by stimulating inhibition and it increases diuresis. It is inferior to digitalis in its therapeutic action because of its irregularity of absorption’. It was used as a digitalis substitute in some situations, providing an alternative in cases that were unresponsive to conventional drugs – although its usefulness was limited due to some unpleasant side-effects such as vomiting and diarrhoea – and could be employed in conditions complicated by kidney dysfunction. Adonis also contains the cardiotonic glycoside adonidin, which had an effective local anaesthetic action. This led to its use in solutions for ophthalmic investigations, and for providing pain relief in inflammatory eye disorders such as iritis and iridocyclitis4 (Martindale 1952). 3 Other Adonis species contain similar cardenolides: A. aestivalis, A. aleppica, A. chrysocyanthus and A. sibir – some of which were used as substitutes for the Summer Adonis (Pauli 1995, 1993; Kopp 1992; Mamadov 1986; Maksiutova & Lazareva 1978). 4 Inflammation of the iris (iritis) of the eye, or of the iris and ciliary body (iridocyclitis).

Adonis vernalis, from Peter Squires, Companion to the Latest Edition of the British Pharmacopoeia, London, 1899.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Cymarin and related compounds (adonin, adonilide) have been isolated from the Amur Adonis (Adonis amurensis) – the roots of which have provided a heart tonic in Chinese medicine. It was recommended for the treatment of congestive heart failure, as well as being an effective diuretic and tranquilliser. Interestingly, an extract preparation developed in Manchuria has been used clinically in the treatment of rheumatic heart disease (Duke & Ayensu 1985). (Image courtesy JD Steakley, Wikimedia Commons)

herbs such as Scilla maritima, Nerium oleander and Adonis vernalis, as well as Lily-of-the-Valley (Convallaria majalis), by evaluating the activity of the various component glycosides: convallatoxin, cymarin, proscillaridin and scillaren. While their activity was found to be fairly equivalent, their effect on the venous system could vary greatly due to different mechanisms of action. The impact of an extract of Winter Adonis (Adonis vernalis) on venous function was stronger than that of Squill (Urginea maritima syn. Scilla maritima), Oleander (Nerium oleander) or Lily-of-the-Valley. Cymarin, which is found in Kombe (Strophanthus kombe) and Adonis vernalis, also had venous activity that was stronger than its cardioactive actions indicated (Lehmann 1984). Urginea maritima (syn. Drimia maritima). (Courtesy Javier Martin, Wikimedia Commons Project)

The 1952 Martindale Extra Pharmacopoeia provided further details regarding the therapeutic value of the Winter Adonis: Adonis vernalis slows the cardiac rate, establishes a more regular rhythm, increases diuresis, abolishes oedema and ascites, and improves the general condition. Best results are obtained in mitral stenosis, pulmonary emphysema, and cardiac insufficiency following sclerosis of the pulmonary artery. It has little use in anginal symptoms and has no effect in syphilitic aortitis. Good results were obtained in cardiac asthma, where cardiosclerosis [arteriosclerosis: hardening of the arteries of the heart] and emphysema were present. It has a more rapid action than digitalis, is not cumulative and is less toxic. The dry extract is preferable to the tincture, the recommended dose being 0.5 g six times a day, reduced in cases of sensitivity or anginal symptoms to 0.5 g three times a day, or 50 drops of 3% tincture.

The entire plant was collected just before flowering and dried. It was also regarded as having stimulant and strengthening properties. In Cyprus the herb tea has continued to be employed as a remedy for dropsy (Georgiades 1987). It is important to appreciate that the use of a herbal cardiotonic often has a valid chemical basis. An interesting study in the 1980s compared the cardiovascular potential of a number of cardiotonic

(Below) Scilla or Squill entry, from the British Pharmacopoeia, 1867.

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White Squill or Sea Onion, Urginea maritima (previously known as Scilla maritima, Urginea scilla or Drimia maritima) is an effective diuretic and cardiac tonic. There are two main cardiac glycosides in Squill bulbs (scillarins A and B), and a number of minor, but quite active, ancillary alkaloids. The herb, however, is not as potent as digitalis. Its clinical use was limited due to bioavailability issues because it was poorly absorbed and rapidly excreted. In an 1893 article T Phillips-Gibson provided an overview of the remedy, commenting: ‘Squills are used as an emetic in whooping-cough, croup, and chronic pulmonary affections, such as catarrh, asthma &c., and also as an expectorant. There are seven preparations recognised in the British Pharmacopoeia, but with the exception of the vinegar and the syrup, they require careful manipulation, and should not be attempted by any but the trained druggist or dispenser’. Syrup of Squill was ‘a favourite remedy for children suffering from croup, the dose being a small teaspoonful at intervals until vomiting is brought up, thus removing the phlegm (Thompson’s Domestic Medicine)’. This does not really sound like much of a great ‘favourite’.

[[cap [[cap

Convallaria majalis.

Lily-of-the-Valley, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

Lily-of-the-Valley (Convallaria majalis) is a familiar cottage garden herb with a long history of clinical use for heart disease. Its cardiotonic properties are similar to digitalis, albeit the effect is much less dramatic and it has particularly useful diuretic attributes. The herbalist Maude Grieve (1931) provided details for its practical use as a mild digitalis substitute, considering it to be well suited for use in valvular heart disease, cardiac debility and dropsy: ‘It slows the disturbed action of a weak irritable heart, whilst at the same time increasing its power. It is a perfectly safe remedy. No harm has been known to occur from taking it in full and frequent doses, it being preferable in this respect to Digitalis, which is apt to accumulate in the blood with poisonous results.’ Even so, the plant contains a number of cardioactive glycosides (e.g. convallarin, convallamarin, convallatoxin) that would suggest exercising care with the use of the herb.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Hawthorn: A Premier Cardiac Tonic

Hawthorn herb is sourced from two species: Crataegus oxyacantha (syn. C. laevigata) and C. monogyna, which belong to the Rosaceae family. The latter is a widespread introduction in the southern temperate regions of Australia: New South Wales, Victoria, South Australia and Tasmania.

Hawthorn fruit is an age-old heart tonic that is currently experiencing a resurgence of popularity. For decades Hawthorn was ignored by medical research because its effects on the heart were not as dramatic as either Lily-of-the-Valley or Foxglove. The testimony of Professor Harvey Wicks Felter (1922) gives a good summary of its activity, providing details regarding its early investigation in America: The English hawthorn seems to have largely escaped the exact investigators of medicinal plants until a quite recent date … it is distinctive in occupying almost wholly a position in cardiac therapy, though recognized to some extent as a general tonic. Investigators are divided as to its activity, some claiming it only as a functional remedy, while others go so far as to claim it curative of many heart irregularities, even in the presence of an actual organic disease of that organ. Among the conditions in which Crataegus is accredited with good work are angina pectoris, endocarditis, myocarditis, and pericarditis, valvular incompetency with or without enlargement of the rings, rheumatism of the heart, dropsy depending on heart disorders, neuralgia of the heart, tachycardia, and in atheromatous conditions of the vessels … There is no doubt, however, of its value in many of the conditions mentioned, especially the functional types; and

there can be no question as to its value as a tonic to the heart muscle. It is not poisonous, has no cumulative effect and apparently from reports of a large number now using it, may be useful to control many of the symptomatic results depending on a badly functioning or tired heart. Crataegus has been suggested to rest that organ and thereby guard against arteriosclerosis.

It is important to realise that the cardiotonic effect of the remedy is progressive, making it a remedy that is best taken for a prolonged period. Over time, studies have progressively revealed the validity of many of the old therapeutic claims, and have even enhanced the herb’s reputation. The plant, which does not contain cardiac glycosides, relies on a combination of flavonoids and oligomeric procyanidins that have other mechanisms of cardiotonic activity. The herb acts by increasing coronary blood flow and facilitating the repair of heart muscle tissue. Research has shown that procyanidins (and not flavonoids such as rutin, vitexin or hyperoside) isolated from Crataegus oxyacantha and C. monogyna were also responsible for a vascular relaxant effect (Kim 2000). In addition, Hawthorn contains crataegic acids with cardiotonic attributes that act to increase coronary blood flow and reduce blood pressure. Catechins possess similar properties. Hawthorn has valuable antioxidant properties and a definite protective action against the build up of cholesterol (atheroma) in the arteries. The herb is suitable for the treatment of mild congestive heart failure, cardiac arrhythmia, coronary artery disease, angina pectoris and hypertension.5 Crataegus can have substantial benefits when used in combination therapies. It can complement the action of drugs like digitalis, providing better clinical results than if the latter was used alone. The conclusions of an extensive review of Hawthorn by Kerry Bone (1992) state: The traditional use of Crataegus for heart disease is well supported by scientific studies, although these 5 I have used this herb for many years and concur completely with its extraordinary clinical value for both humans and various species of native wildlife (CJW).

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studies tend to suggest that the leaves are more active than the berries. However, as is often the case, scientific investigation has also revealed possibilities for important new actions for Crataegus. Their significance will largely be determined by a better understanding of the value of antioxidant therapy in the treatment and prevention of many common health disorders.

Clinical research continues to verify the traditional uses of this herb, suggesting particular value for the early stages of congestive cardiac failure and in the treatment of hypertension (Altern Med Rev 2010, 1998; Pittler 2008; Holubarsch 2008).

Chinese Hawthorn.

Like the European Hawthorn, Chinese Hawthorn (Crataegus pinnatifida var. major and C. cuneata) has cardiovascular tonic properties, as well as cholesterol-lowering and hypotensive activity. The stir-fried fruit has been traditionally employed as a digestive tonic for treating dyspepsia, fatty food stagnation, and stomach or abdominal distension and fullness. The raw herb (fruit) has pain-relieving properties and acts to invigorate the circulation and remove blood stasis.Thus, it has been used for treating gynaecological disorders (menorrhagia, amenorrhoea, post-partum abdominal pain), as well as angina. Additionally, it has been employed as a lactagogue (to stimulate milk secretion), a taeniacide (to expel tapeworms), and the carbonised fruit as an astringent antidysenteric agent (Lou 1987; Yeung 1985; Bensky & Gamble 1986).

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The Medicinal Rose

Roses have been among the most prized and familiar plants in the cottage garden.6 It may, however, come as a surprise to learn that since ancient times Rose petals have been accorded great respect as a medicine, as well as a colouring agent and a fragrant additive. Numerous species have medicinal properties – a few of which earned official recognition in the various pharmacopoeias. They include the China Rose (Rosa chinensis), Apothecary’s Rose (R. gallica), Cabbage Rose (R. centifolia), Damask Rose (R. damascena), Sweetbriar or Eglantine (R. eglanteria) and the Chestnut Rose (R. roxburghii). The Damask Rose provides a good illustration of the validation of a traditional remedy by modern science. In general, Rose oil has antibacterial and antioxidant properties that are particularly well suited for use in cosmetics and skin formulations. Investigations of the antimicrobial efficacy of Rosa damascena absolute and essential oil (which contain high levels of phenolics7) showed strong antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Chromobacterium violaceum and Erwinia carotovora. This was linked to the phenyl ethyl alcohol content (PEA 72–78%) (Ulusoy 2009). The oil’s substantial antibacterial properties against Propionibacterium acnes also support its use in acne treatments (Zu 2010).8 However the hydrosol preparation, which had significantly lower levels of phenyl ethyl alcohol than the absolute or essential oil, showed no antimicrobial activity (Ulusoy 2009).9

6 Species naturalised in Australia include R. bracteata, R. canina, R. chinensis, Rosa x damascena, R. gallica, R. indica, R. laevigata, R. luciae, R. multiflora, R. odorata, R. roxburghii and R. rubiginosa. 7 The total phenolic contents of the absolute was extremely high (2134 gallic acid equivalent [GAE] per mg/L), although the level in the essential oil was also quite good (849 GAE/mg/L). In comparison, that of hydrosol was very low (5 GAE/mg/L) (Ulusoy 2009). 8 Cinnamon, Thyme and Lavender oils have similar antibacterial potential (Zu 2010). 9 Rose hydrosol: PEA (24%) – as well as geraniol (31%), citronellol (29.5%) and nerol (16%). PEA, which has a rose-like aroma, has been utilised as a fragrance ingredient in cosmetic products and culinary items such as beer, wine, olive oil, grapes, tea, apple juice and even coffee (Ulusoy 2009).

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

The wild Damask Rose (Rosa damascena), originally from the Balkans and Asia Minor, is the source of Attar of Roses – the Rose oil typically used for perfumes and as a flavouring. It is also reputed to have rejuvenation properties. Traditionally, Attar of Roses was inhaled to calm the nerves and promote sleep – as well as being useful for menstrual distress. Damask Rose essential oil is primarily composed of hexatriacontane (24.6%), geraniol (15.05%), nonadecene (18.56%) and tricosane (16.68%) – as well as smaller amounts of linalool (3.8%), nerol (3.05%) and pentacosane (3.37%) (Yassa 2009). Other analyses indicate the composition can vary somewhat: citronellol (15.9–35.3%), geraniol (8.3–30.2%), nonadecane [sic] (4.5–16.0%), heneicosane (2.6–7.9%), linalool (0.7–2.8%) and nerol (4.0–9.6%) (Verma 2011). (Image courtesy Kurt Stüber, CC-by-SA 3.0) Rose preparations, from the British Pharmacopoeia, 1867.

Rosa gallica var. officinalis.

Maude Grieve (1931) recorded the following interesting details regarding the official Apothecary’s Rose:

Confection of Red Rose, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

The British Pharmacopoeia directs that Red Rose petals are to be obtained only from R. gallica, of which, however,

there are many variations, in fact there are practically no pure R. gallica now to be had, only hybrids, so that

FLOWERS OF THE MATERIA MEDICA the exact requirements of the British Pharmacopoeia are difficult to follow. Those used in medicine and generally appearing in commerce are actually any scented roses of a deep red colour, or when dried of a deep rose tint. The main point is that the petals suitable for medicinal purposes must yield a deep rose-coloured and somewhat astringent and fragrant infusion when boiling water is poured upon them.

In particular, Rose water ointment has long been highly regarded as a soothing agent for skin problems (rough, dry or chapped skin). A tincture made from Rose petals provided an anti-haemorrhagic agent and stomachic (tonic for gastric function). Rose oil was particularly valued for its soothing effects on the nerves and was used as a remedy for insomnia and depression.10 It takes a staggering number of roses to make an ounce of Rose oil – which, incidentally, is not the anticipated bright red hue but assumes an orange-green colour. Other Rose-based preparations that have been utilised medicinally include Rose-petal tea, Rose honey and Rose vinegar.

The Aromatic Rose

The production of Rose essential oil is a labourintensive process. The freshly opened flowers are hand-harvested before dawn to avoid the drying effects of the sun on the blooms – an important consideration that can significantly affect the oil yield. The Damask Rose is the Pink flowered Rose. main source of Attar of Roses (Rose absolute) – a high-priced concentrated fragrance that is extracted by a solvent or supercritical carbon dioxide extraction. The yield is 5–10 times that obtained by stem distillation, a process used to produce Rose Otto (Ulusoy 2009; Widrlechner 1981). Rose absolute, which is favoured by the perfumery 10 Many essential oils, including that of the rose, have anxiolytic attributes that are associated with a relaxant effect (Hongratanaworakit 2009; Setzer 2009). Experimentally, rose oil injections were noted to have an anti-seizure effect, and investigations have subsequently focused on the neuroprotective potential of various Rose-derived extracts and oils (Awale 2011; Jung Choi 2009; Ramezani 2008).

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industry, primarily contains phenylethyl alcohol (72–78%), with lower levels of citronellol (10–11%) and nerol (3–4%) – as well as nonadecane (4%) or geraniol (5.6%). The absolute also contains β-carotene (422 ppm) and tocopherol (ɑ-tocopherol 2397 ppm; y-tocopherol 422 ppm) at levels higher than is found in the essential oil or hydrosol (Ulusoy 2009).   There are some interesting accounts of early Australian attempts at the extraction of Rose perfumes. A report by Mr BG Hardy (1894) eloquently illustrates the frust-ration associated with problematic weather conditions and difficulties in supply: I must state a matter for considerable regret, inasmuch as on my arrival [at the nursery] the weather had a promising appearance for a continuance of fine weather, but immediately after I had commenced work, an unfavourable change took place, and heavy rains set in. This, unfortunately, continued more or less for thirtyfive days, with only two exceptions, and during that period over 14 inches of rain fell. It is hardly necessary for me to point out how detrimental this would be to the retention of the perfume by the flowers until I could work them, and in almost every case, all through the work, I had to express the water from the blooms before I could lay them down, thereby losing a very valuable portion of their odour. White rosebud.

He paints a vivid picture of the challenges encountered: Beyond this, I was, throughout the work, at very considerable disadvantage from insufficient space and the primitive nature of the building placed at my disposal for operating in, and the irregular and curtailed supply for flowers. On the latter point, I may explain that I never commenced work on a flower without first inquiring if there would be a sufficient supply of bloom available at regular intervals to carry the experiment to completion, but I frequently found,

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary when at actual work, that from some cause or other I could not obtain a recharge for sometimes nearly a week instead of daily, and at other times the bloom allowed me totally ceased after, perhaps, one, two or three changes, in place of at least a dozen required

While a number of oil samples were not as complete as he had wished, he had certainly demonstrated the viability of the venture: ‘Nevertheless, in every case they are satisfactory in quality and strength, as far as the opportunity would allow, and demonstrate the facts that under more favourable circumstances, articles of high quality may be produced and carried forward to commercial success’. Perfumes from Bouvardia, Tuberose, White and Red Roses, Carnations, Phlox and Spikehead were all of a valuable quality. He also considered that: ‘I would express my opinion that … it would be found that many of our native plant might profitably be brought into cultivation for perfumery purposes, and give odours of a special value to the trade for manufacturing new preparations, and without doubt the very fact of offering new specialities in Australian perfumes would operate beneficially in the sale of all our other perfume products.’

Remedies from Rosehips

Rosehips.

Confection of Dog Rose hips, from Phillips’ Translation of the Pharmacopoeia Londonensis, 184

Wildflower perfume and Boronia hand and body lotion. Australian wildflowers have a wonderful evocative scent of the native bush. Of these, Boronia, sourced from Boronia megastigma, is a premier native wildflower perfume of international fame.11 (Images courtesy House of Sharday, Australia)

Citrus fruits such as lemons and oranges have long been valued for their vitamin C content, although there are other plants that qualify as superior resources, particularly rosehips (Rosebush fruits). These can be easily sourced from the various common species, including the Dog Rose (Rosa canina), the Field Rose (R. arvensis), the Downy-leaved Dog Rose (R. mollis) and the Potato Rose (R. rugosa). In general, the fruits contain malic and citric acids, sugars, essential fatty acids, fat-soluble vitamins (β-carotene, lycopene, tocopherol), flavonoids, various minerals12, a trace of tannin, and ascorbic acid 0.4–1.0 per cent. An analysis 11 See Volume 1 for further details. 12 Rose fruit, flesh and seeds can contain quite good levels of phosphorus, potassium, calcium, magnesium and iron. Sodium levels are low. Manganese, zinc, copper and boron may also be present (Kazaz 2009).

FLOWERS OF THE MATERIA MEDICA

of Rosa micrantha found ascorbic acid was abundant in all parts of the rose, albeit richest in the ripening hips (944 mg/100 g). This was comparable to that of other species (726–943 mg/100 g)13: R. canina, R. dumalis, R. dumalis subsp. boissieri, R. dumalis subsp. antalyensis, R. micrantha, R. pisiformis, R. pulverulenta, R. rubiginosa and R. villosa. To put this in perspective, the vitamin C content of R. rubiginosa at 400 mg/100 g was 10-fold higher than orange juice, and 15 times that found in citrus fruits. The dried fruit, unfortunately, loses the majority (95%) of its vitamin C content (Guimaraes 2010; Moure 2001; Hornero-Mendez & Minguez-Mosquera 2000). The British Pharmaceutical Codex of 1949 noted: Rose fruit is a rich natural source of ascorbic acid, and contains from three to four times as much of this constituent as black currant, and about twenty times as much as orange juice. A palatable syrup suitable for infants and children is prepared from the fresh fruit and has a standardised ascorbic acid content of 2 milligrams per millilitre. The daily prophylactic dose of this syrup for a child in 12.5 millilitres (190 minims), but as a dietary supplement it is usual to give about 4 to 8 millilitres (60 to 120 minims). Rose fruit is also employed in the preparation of a confection which is occasionally used as pill excipient.

Additionally, Rosehips could be stored frozen until required for making syrup. In folk medicine traditions Rosa canina fruit (decoction or syrup) was employed in an interesting range of disorders – malaria, haemorrhoids, hepatitis, stomach-ache and bronchitis. The fruit of Rosa sempervirens was used similarly in Turkey (Tuzlaci & Aymaz 2001). Doubtless the support that vitamin C provides the immune system would play an important part in the therapeutic efficacy of rosehip extracts – which possess significant antioxidant properties (Poblete 2009; Buricova & Reblova 2008; Speisky 2006). Carotenoids are another important component of rosehips that are responsible for the 13 Another review gives a much greater variation in vitamin C levels, ranging from 106–2712 mg/100 g. Levels in the fruit flesh of R. canina and R. damascena were found to be the highest (2200 and 546 mg/100 g respectively), substantially more than was present in the seeds (306 and 145 mg/100 g respectively). ɑ-tocopherol (ug/g) was higher in R. canina fruit (34 ug) than the fruit flesh (21.6 ug) and lowest in the seed (8 ug) – which was substantially higher than for R. damascena (7 ug fruit, 5.35 ug flesh and 5.25 ug seed). β-carotene levels did not alter significantly in the different plant parts of R. damascena (2.95–3.7 ug) and, although levels in R. canina were similar (2.6-3–25 ug) in fruit and fruit flesh, that of the seed of was quite low (0.18 ug) (Kazaz 2009).

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intense colouring of the hip (which can vary from rich yellow to a bright red) and rose petals. Rosa micrantha contained high levels of β-carotene (46–62 mg/100 g) and lycopene (17–59 mg/g) in the hips (overripe and ripening fruit) and flower petals. The content was similar in Spanish samples of Rosa rubiginosa hips (49.7 mg and 39.2 mg, respectively). A range of other carotenoids are also present, notably rubixanthin, gazaniaxanthin, β-cryptoxanthin, and zeaxanthin (Hornero-Mendez & Minguez-Mosquera 2000).

Rosa roxburghii. (Courtesy Salvor Gissurardottir)

Popular Rosehip resources also include the Cherokee Rose (R. laevigata), the Multiflora or English ‘Tea Rose’ (R. multiflora), and the Chestnut Rose (R. roxburghii). The latter is a commercial source of rosehip powder from China. The vitamin C content is 5–7 per cent (794–2391 mg/100 g fresh fruit) and vitamin P (flavonoid content: 5981– 12895 mg/100 g) (Nantong Sihai Plant Extracts Co. Ltd, www.made-in-china.com). Rosa roxburghii is considered to have useful antioxidant, circulatory and cardiovascular tonic properties. Experimentally, extracts demonstrated anti-arteriosclerosis activity and benefits for cholesterol levels that support its use for cardiovascular disorders. The herb is also considered to have rejuvenation, immune supportive and anticancer effects (Burke 2005; van Rensburg 2005; Zhang 2001; Ma 1997; Hu 1994). Other species appear to possess similar activity. Rosa damascena extracts (buds and component flavonoids) possess cardioactive properties that support its use as a cardiotonic14 (Kwon 2010; Yassa 2009) – and R. davurica (fruit extracts) demonstrated anti-ischaemic properties with cardioprotective potential (Jiao 2004). 14 A number of terpenes (ɑ-pinene, β-pinene, citronellol, linalool) that are found in essential oils possess hypotensive activity (Menezes 2010).

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Rosehip Seed Oil

Rosehip – cut fruit with seeds.

An evaluation of essential fatty acids in the seeds of R. damascena and R. canina have confirmed a high unsaturated fatty acid content, characterised by moderate levels of oleic acid (24 and 22%, respectively) and ɑ-linolenic acid (15 and 20%, respectively), with much higher levels of linoleic acid (54 and 49%, respectively). Overall, low levels of palmitic (5%) and stearic acids (2–3%) were present. This was comparable with other studies of these oil components15 (Kazaz 2009). Rosehip oil can be of benefit in numerous irritable skin disorders, including eczema, skin ulcers, neurodermatitis (a highly discomforting inflammatory skin disorder associated with chronic itching and scratching) and cheilitis (inflammation of the lip). The soothing antiinflammatory effects can be enhanced by combination with fat-soluble vitamins. However, those individuals who are susceptible to contact allergy problems with rosehip and rose oils should avoid these products (Chrubasik 2008; Shabykin & Godorazhi 1967).

Sukin Rosehip Oil. (Courtesy Sukin Organics Pty Ltd, Australia)

Rosehips were traditionally de-seeded, with the best preparations utilising the fresh hip. The seeds within, which are covered by a hairy skin, would therefore have been discarded. However, times change, and the seeds are now considered to be an excellent oil resource with a high essential fatty acid content (oleic, linolenic and linoleic fatty acids) of value to the cosmetic industry. These unsaturated fatty acids can be obtained from numerous species: R. canina, R. dumalis subsp. boissieri, R. dumalis subsp. antalysensis, R. micrantha, R. pisiformis, R. pulverulenta, R. rubiginosa, R. villosa. In addition, palmitic acid was identified as the main fatty acid in the petals and fertilised flowers of R. micrantha (Guimaraes 2010).

The Mosqueta Rose (Rosa rubiginosa, syn. R. eglanteria) is native to South America and is a rich rosehip seed oil resource. It has been traditionally utilised as a healing agent that was particularly valued for open wounds and ulceration (Santos 2009; Moreno-Gimenez 1990). (Image courtesy Adrian Barabino) 15 Oleic (16–22%), lineolic (36–55%), ɑ-linolenic (20–26.5%), palmitic (3.6–8%), and stearic (2–3%) acids (Kazaz 2009).

FLOWERS OF THE MATERIA MEDICA

A number of Rose species possess particularly good anti-inflammatory and analgesic properties – they include the Persian Rose, Rosa damascena (hydroalcoholic extracts of dried petals, but not the petal oil), R. canina (rosehip extracts), R. multiflora (rosehip extracts), and R. rugosa (root extracts). The latter contains tormentic acid (a triterpene saponin) with anti-inflammatory activity16 (An 2011; Lattanzio 2011; Hajhashemi 2010; Yassa 2009; Zhang 2008; Jung 2005). Research over the last few decades has shown valuable therapeutic applications for the rosehip. Rosa canina hip powder has good potential for clinical use as an anti-inflammatory and analgesic in osteoarthritis, rheumatoid arthritis and low back pain (Olsen 2011; Willich 2010; Christensen 2008; Chrubasik 2008) – although there is some controversy with regard to its efficacy (Kirkeskov 2011). Rosehip extracts contain triterpenes with antimicrobial, immunomodulatory and anti-inflammatory properties – oleanolic, betulinic and ursolic acids, with a synergistic action that contributes to their efficacy (Saaby 2010). Certainly, these studies suggest that Rose-based additives could have more extensive applications than is currently appreciated by the pharmaceutical and cosmetic industries – as well as culinary uses as antioxidant and antimicrobial flavouring agents (Egea 2010; Guimaraes 2010; Yassa 2009). Rosa davurica is a northern Asian species (China, Mongolia, Korea, Siberia) that has been utilised as an anti-inflammatory remedy and to treat skin growths. Dried leaf extracts possess analgesic and antiinflammatory properties – as well as anti-angiogenic (preventing tumour metastasis) and antioxidant effects that could help explain its use for tumorous growths (Jung 2011). Rosehip powder (from Rosa canina) has shown some interesting anticancer and radioprotective properties. It had an inhibitory effect on melanoma (skin cancer) cells, as well as a supportive (synergistic) effect when combined with the anticancer drug 5-fluorouracil (Adrucil) in endometrial cancer cell studies. Flavonoids (proanthocyanidins17) from rosehip extracts were of particular interest as potent inhibitors of melanin biosynthesis (Dai 2011; Fujii

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2011, 2009; Akhmadieva 1993). Hydrolysable tannins are among the main phytochemicals present in rose extracts. Gallic acid (and derivatives) were identified among the main antioxidant, anti-inflammatory, antimutagenic and anticancer components of Rosa rugosa extracts. Polysaccharides with antioxidant activity were also present (Choi 2009; Ng 2004). The potent antioxidant properties of Rosa canina (rosehips) were likewise linked to its phenolic components18 (Kilicgun & Altmer 2010) – as were benefits for lipid metabolism from R. centifolia extracts (petal extracts and rose ellagitannins)19 (Kondo 2011).

Multipurpose Rose Remedies

Numerous studies have shown antibacterial properties (including activity against dental bacteria) for various rose products – which certainly support their healing reputation. Indeed, extracts prepared from Damask Rose receptacles have demonstrated a broad range of antimicrobial activity against Candida albicans,

Scanning electron micrograph showing Salmonella typhimurium (red) invading cultured human cells. Salmonella are gram-negative pathogens that are responsible for food poisoning and food spoilage. Extracts of the Damask Rose (receptacles) and the Multiflora Rose (Rosa multiflora, flower and leaf ) possess good activity against Salmonella typhimurium (Frey & Meyers 2010; Talib & Mahasneh 2010). (Image courtesy Rocky Mountain Laboratories, NIAID)

16 Rosa rugosa (white petal extracts) has also demonstrated anti-allergic, antioxidant and anti-inflammatory activity (Jeon 2009; Park 2009).

18 A study of Rosa micrantha linked antioxidant activity with the level of phenolic components. The highest levels (mg/GAE/g ext) was found in the fertilised flowers (527 mg), slightly less in the petals (424 mg), and lower levels in over-ripe (304 mg), ripening (188 mg) and unripe (142 mg) hips (Guimaraes 2010).

17 Quercetin demonstrated a particularly potent activity for the inhibition of melanin biosynthesis, however the level present in rosehip extracts was low (Fujii 2011).

19 Some studies suggest rosehip seed extracts have anticholesterol and metabolic regulating activity with potential to assist weight control (Chrubasik 2008).

X

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhimurium and Bacillus cereus (Talib & Mahasneh 2010). The antibacterial properties of Rose extracts extend to dental pathogens and it has been employed in treatments for aphthous stomatitis (canker sore), which is an extremely difficult condition to treat. This is a form of mucous membrane inflammation of the mouth that is often associated with recurrent painful ulceration. Clinically, a mouthwash containing Rosa damascena extract gave good results (Hoseinpour 2011; Shokouhinejad 2010).

Antiviral Tannins

Wild Rose, Rosa canina, a Bach Flower Remedy. This remedy is to help with a sense of apathy and disinterest in life – with an accompanying feeling of sadness and depression. (Image courtesy Martin & Pleasance, Port Melbourne)

Rosa species have been traditionally utilised as antidiarrhoeal remedies – an activity that has been linked to their tannin (polyphenol) components. They include Rosa canina, R. centifolia, R. sempervirens, R. eglanteria, R. laevigata and R. rugosa (Kamijo 2008; Tuzlaci & Aymaz 2001; Lust 1974). Indeed, Rosa canina (leaf extracts) demonstrated very good antidiarrhoeal activity in animal studies (Mandade 2011). This activity has been supported by investigations showing diverse antimicrobial properties for the genus. Interestingly, Rosa rugosa (flower petal) extracts showed excellent antibacterial activity against various intestinal bacteria (Bacteroides vulgatus, Escherichia coli, Staphylococcus aureus and Bacillus cereus). This was linked to the hydrolysable tannin components, notably rugosins and tellimagrandins. Tellimagrandin I was of special interest due to an antibacterial drugpotentiation (synergistic activity) with prospects for clinical use – for example, in combination with tetracycline or oxacillin to enhance the efficacy of these antibiotics (Tamura 2010; Kamijo 2008; Shiota 2004, 2000).

Tellimagrandins and similar phenolics (ellagitannins) are found in Clove (Syzygium aromaticum), Geum (Geum japonicum) (Kurokawa 1998) – and some Eucalyptus species – including E. globulus, a massive specimen of which is shown here, and E. nitens (Barry 2001; Hou 2000). (Image courtesy Kim and Forest Starr, Hawaii)

Antiviral studies of the Rosaceae have shown that Rosa rugosa and Prunus sargentii have experimental HIV-inhibitory activity. The triterpenoid rosamultin was identified as the most active component of Rose root extracts (Park 2005). Tannins also appear to have significant influence on the antiviral properties of various plant extracts – although this activity is likely to be due to a natural combination of the component phenolics rather than an individual component. Indeed, tellimagrandin I, eugeniin and casuarictin from Rosa rugosa flower extract have demonstrated antiviral potential against the hepatitis C virus (Tamura 2010). Tellimagrandin II has shown anti-herpes virus properties – although studies have also shown that extracts of Geum japonicum and Rhus javanica, which contain eugeniin as a major anti-herpes component, possessed activity against the cold sore virus (Herpes

FLOWERS OF THE MATERIA MEDICA

simplex) (Kurokawa 1998 & 1995). Both species show immunological activity with a significant cytomegalovirus inhibitory effect. Terminalia chebula and Syzygium aromaticum were found to be similarly effective (Shiraki 1998, Yukawa 1996). Geum japonicum has been used in traditional medicine as an astringent and diuretic agent. Extracts of the herb have shown anticancer and antiviral (anti-AIDS) potential (Heo 2008;

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Rosehip powder, in combination with probiotic bacteria (Lactobacillus plantarum) has interesting potential for regulating gastrointestinal function (decreased flatulence, increased stool volume, softer stools) – with an extract of rosehip seeds also showing anti-ulcer activity. A rosehip and lactobacillus combination demonstrated experimental benefits for tissue recovery after colonic injury stress, which led to suggestions for its use as a pre-treatment in surgical procedures – for example, organ transplants, colon or vascular surgery (Chrubasik 2008; Hakansson 2006). A couple of other intriguing studies have shown Rosa canina extracts could act against the formation of calcium oxalate stones, which indicates that it may have potential for the prevention and treatment of urolithiasis (kidney stones) (Tayefi-Nasrabadi 2011; Chrubasik 2008). This certainly deserves further investigation.

Geum japonicum. (Courtesy Judy Monkey, flickr)

Kageyama 1996). It also contains various triterpenes with experimental anti-HIV activity, such as maslinic acid and ursolic acid (Xu 1996). Tannins with anticoagulant properties have also been isolated (Dong 1998). Herbal extracts have shown significant antioxidant and radical scavenging properties that were linked to trihydroxybenzaldehyde (3,4,5-THBA)20 – 105 mg/kg in leaf; 240 mg/kg in stem (Kim 2006). Recent investigations have specifically focused on regenerative effects of the herb and an active component (cardiogenin) on the myocardium – suggesting the remedy has extensive potential for facilitating recovery from heart attack (Cheng 2009; Li 2006). Two species of Geum are found in Australia: G. talbotianum (Tasmania) and G. urbanum (NSW and Victoria) – albeit their medicinal potential is unknown. 20 Synonym: pyrogallol-5-carboxaldehyde.

In Chinese medicine, Rosa rugosa leaf tea has long been recommended as a febrifuge. The flowers, however, had a more extensive medicinal reputation: promotion of blood circulation, for bleeding problems (haematemesis, haemoptysis), digestive disorders (dyspepsia, stomach-ache) and the regulation of spleen and liver function (hepatitis). The flower could also be applied locally to treat infections such as an abscess or a breast boil in nursing mothers (Duke & Ayensu 1985). Furthermore, the root has been traditionally employed as a cough remedy and for the treatment of diabetes mellitus (Jeon 2009). Rosa rugosa seed oil is high in linoleic and linolenic acids (44.5% and 32%, respectively), as well as containing a moderate amount of palmitic acid (17.6%) (Duke & Ayensu 1985).

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

  The Cherokee Rose

Cherokee Rose, Rosa laevigata. (Courtesy Bron Praslicka, flickr)

Rosa laevigata (fruit, roots and leaves) has traditionally been utilised as an astringent, carminative, antimicrobial, tonic and healing remedy for innumerable conditions: urinary tract disorders (enuresis, polyuria, chronic infections), gynaecological problems (dysmenorrhoea, menorrhagia, pelvic inflammation, cervicitis), gastrointestinal distress (dysentery, diarrhoea, enteritis), male sexual problems (spermatorrhoea, premature ejaculation) and respiratory distress (cough, bronchitis). The leaves have been highly valued as a vulnerary (healing agent) (He 2009; Duke & Ayensu 1985). Triterpenes were isolated from leaf and root extracts with anti-inflammatory and antifungal (anti-Candida) properties (Zeng 2011; Yuan 2008). Root extracts have also shown good hepatoprotective activity (He 2009). Interestingly, the plant contains an antioxidant brown pigment that may have potential uses as a food additive (Xiao 2011) The Chinese Tea Rose (Rosa chinensis) is another of the red roses with a substantial medicinal reputation. In Belize it provided an astringent, cooling remedy for feverish conditions and childhood diarrhoea. A tonic infusion was prepared from a single red rose, with nine leaves, steeped in a cup of boiling water for 15 minutes. A stronger infusion employed three red roses with a handful of leaves (similarly prepared) for adult diarrhoea or haemorrhagic problems. Flower extracts possess broad spectrum antifungal and anti-candidal activity, as well

Rosa chinensis.

as antibacterial properties (Arvigo & Balick 1993). In Chinese traditions the fruit was applied locally to heal ulcers, wounds and sprains. The decoction (leaf, fruit, root) was taken as an antirheumatic and anti-arthritic remedy, to alleviate haematuria (blood in the urine), as an antitussive for cough or applied locally for skin infections (boils). The flower buds were recommended for dysmenorrhoea, circulatory problems and stomach pain (Duke & Ayensu 1985). The analgesic, antimicrobial and anti-inflammatory activities of other Rosa species support similar medicinal reputations. Rosa damascena (extracts and essential oil) has bronchodilatory and antitussive effects useful for cough relief – with some extracts exhibiting activity comparable to the anti-asthmatic drug theophylline (Rakhshandah 2010). Rosa centifolia flower extracts have antitussive properties comparable to codeine phosphate, which support the herb’s traditional use for respiratory distress. The essential oil was reported to have gastrointestinal relaxant and bronchodilatory effects. In addition, the flowers have been utilised as an antibacterial remedy (including the treatment of conjunctivitis) and as a remedy for diabetes (Anand Sankar 2011). Interestingly, recent studies support the antidiabetic potential of Rosehip extracts and Rosa damascena flower extracts (Andersson 2011; Gholamhoseinian 2009). Trans-tiliroside from rosehip and seed extracts was found to have a blood glucose-lowering effect, as well as beneficial effects on lipid metabolism (Chrubasik 2008). The Provence or Cabbage Rose (Rosa centifolia) is a hybrid rose from eastern Caucasia that is one of the oldest cultivated roses and the source of Rose

FLOWERS OF THE MATERIA MEDICA (Left) Rose water elixir. (Courtesy D McCarthy, www.elixirsoflife.co.uk)

(Below) Rosa centifolia foliacea, by the French botanical artist Pierre-Joseph Redouté (1759– 1840).

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into a polyherbal formulation (V-Gel) that has a good clinical reputation for the treatment of vaginal and cervical inflammation. It is suitable for use in chronic conditions and in the post-partum period (following childbirth). The gel is composed of a number of herbs with antimicrobial, disinfectant, astringent, anti-inflammatory and healing properties: Berberis aristata, Neem (Azadirachta indica), Vitex negundo, Cardamomum (Elettaria cardamomum), Henna (Lawsonia inermis), Parmelia perlata (lichen), Cedrus deodara, Tagetes erecta, Boerhaavia diffusa, Nelumbo nucifera and Anethum sowa (Ranjana & Misra 2001). V-Gel was shown to be effective against the causative agents for trichomonal vaginitis and vaginal candidiasis, as well as some non-specific organisms (e.g. Gonococcus vaginalis) (Vermani & Garg 2002).

Rosa multiflora. (Courtesy Ronnie J Ortiz)

water. The tea has aperient properties – as well as being used as a styptic (infusion, powder or as a tincture) for treating haemorrhage (Lust 1974). The soothing, anti-inflammatory and antimicrobial properties of Rosa centifolia has seen it incorporated

The Multiflora Rose (Rosa multiflora) has an equally potent antimicrobial reputation. The leaves were poulticed on sores, while the fruit and root were useful for ‘foul injuries’, sores, sprains and wounds – which suggests exceptionally good antibacterial and healing properties. Studies have confirmed that extracts of the leaf, stems and flowers were bactericidal (Duke & Ayensu 1985). In Chinese traditions this rose is highly regarded as an astringent, carminative, diuretic and wound-healing remedy. Similar to various other species, the root has been utilised for rheumatoid arthritis, skin disorders and scabies infections (Duke & Ayensu 1985). Root extracts, which contain condensed tannins, have shown immunomodulatory and anti-inflammatory properties with potential for the treatment of allergic

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

and inflammatory skin disorders such as dermatitis and psoriasis. The rosehip extract also possessed antiinflammatory and analgesic potential (Park 2011, 2010; Zhang 2008). In addition, the fruit has been utilised as an antidote for fish poisoning (Duke & Ayensu 1985).

Rosa multiflora fruit are rich in carotene (81 mg/100 g) and vitamin C, and contain multiflorin (Duke & Ayensu 1985). The latter is of interest as multiflorin A (a kaempferol glycoside), isolated from peach leaf extracts, has shown anti-hyperglycaemic properties via inhibition of glucose absorption in the intestine. Prior studies have also suggested that multiflorins A and B have purgative potential (Shirosaki 2012). In addition, the UVB protective effects of peach flower extracts were linked to the presence of multiflorin B (Kim 2002). (Image courtesy Susan Sweeney)

Fragrance and Flavourings in Pharmacy

An important, often underestimated, aspect of the traditional medicine chest is a diverse range of flavouring components, the majority of which have been in use for centuries. Innumerable oils that possess powerful aromatic flavouring qualities are utilised as carminative agents, to soothe gastric distress. Many essential oils are also potent antimicrobial candidates and there has been an enormous amount of research in recent years focusing on this aspect of their medicinal potential. The early chemists in the Australian colony took a keen interest in aromatics and flavourings, although a lack of chemical and entrepreneurial expertise appears to have hampered their commercial success. Joseph Maiden lamented:

Official recommendations for the use of Orange peel: syrup, tincture and wine preparations from Peter Squires, Companion to the latest edition of the British Pharmacopoeia, London, 1899.

Lemon continues to be an important flavouring for medicinal and culinary use. It has additional value as a respected vitamin C resource. (Courtesy Dr Reckeweg & Co., Bensheim, Germany)

FLOWERS OF THE MATERIA MEDICA

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Official recommendations for the use of Lemon peel: oil syrup and tincture preparations from Peter Squires, Companion to the latest edition of the British Pharmacopoeia, London, 1899. At present it unfortunately is frequently the case that large quantities of Citrus fruits rot on the ground, or are otherwise underutilised, simply because it does not pay to take them to market. In Southern France (Sicily and South Italy in particular), oils are obtained from the rinds of the fruit thus left on the growers’ hands. I quite think that the utilisation of surplus and inferior fruit in this way should be enquired into in our own Colony … Orange oil is also made from the scarcely ripe fruits of both sweet and bitter oranges. It is chiefly used in perfumery, and in the fabrication of liqueurs. Oil of lemons should certainly be made in Australia to satisfy all local requirements, and to provide a quantity for export. It is used largely for flavouring (in cookery, aerated waters, &c), perfumery &c. Some is already made in the Australian colonies, if the advertisement of a certain aerated-waters firm is to be taken literally … While dealing with rinds, it would be borne in mind that the peel of the bitter orange is very extensively used in medicine, the Colonies alone

Tincture of Lemon: prepared by an Australian manufacturer – Taylors Elliotts & Australian Drug Pty Ltd, Brisbane. consuming many tons per annum, but the supplies from local sources are small and uncertain. Orangeflower water and oil of Neroli (the latter being the essential oil which perfumes the former), are prepared by subjecting the flowers of both bitter and sweet orange to distillation. These products are valuable, and that they can be remuneratively manufactured in this Colony I have no doubt (Maiden 1892).

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Since this time the market for essential oils in Australia has boomed – with a remarkable range of high quality products sourced from both traditional and innovative native resources.

Orange tincture. (Courtesy The Apothecary, Cairns) (Right) Orange oil. (Courtesy The Apothecary, Cairns)

Citrus aurantium, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. J M’Gregor-Robertson, in The Household Physician (1908), commented that: ‘The [rind of the] Bitter or Seville orange … is rich in flavouring oil, and is largely used for flavouring, and for the extraction of tincture, to be employed as an aromatic tonic. The flavour of the liqueur curaçao is due to the bitter orange. From the flower of this variety, also, the finest orange flower water is distilled. From orange-flowers another oil is obtained – the oil of neroli’ (M’Gregor-Robertson 1908).

Table 1.1 Overview of the Main Essential Oil-yielding Herbs and Spices with Flavouring Qualities that are Utilised in Pharmacy (Note: This table does not discuss the aromatherapy uses of these oils.) Flavouring component (official source) Aniseed (Pimpinella anisum) Star Anise (Illicium verum)

Oil composition (Evans 2002) Medicinal qualities and notes (British Pharmaceutical Codex: BPC 1968; BPC 1934) Anise oil: Aniseed and Star Anise have very similar chemical constituents, primarily anethole 80–90%. Both are used for the production of anise oil (Evans 2002). Other components: chavicol methyl ether, p-methoxyphenylacetone, safrole. Attributes: carminative, mild expectorant Uses: • Anise oil is used in mixtures and cough lozenges, often in combination with liquorice (BPC 1968). • Aromatic, carminative. Used internally as galactagogue, to relieve flatulence; flavouring to mask unpleasant odour of remedies; externally as liniment and ointment in painful conditions, and in pediculosis (Merck Index 1940).

FLOWERS OF THE MATERIA MEDICA Camphor (Cinnamomum camphora)

Caraway (Carum carvi)

Cardamomum (Elettaria cardamomum var. misicula)

Cinnamon, Cassia bark (Cinnamomum zeylanicum)

Clove (Syzygium aromaticum)

Coriander (Coriandrum sativum)

Dill (Antheum graveolens)

Camphor oil: camphor, safrole, borneol, heliotropin, vanillin, terpineol, plus sesquiterpene alcohols (Evans 2002). Attributes: carminative; rubefacient Uses: • Mild antiseptic, carminative; rectified camphor oil (a by-product of camphor manufacture) has been employed as a rubefacient and mild counter-irritant to rheumatic and inflamed joints. It may be applied undiluted or mixed with olive oil or methyl salicylate. Also used as parasiticide (BPC 1934). • Stimulant, antiseptic, rubefacient, parasiticide; external use with olive oil as liniment for rheumatism, neuralgia, myalgia, lumbago, bruises, sprains; for parasitic skin diseases (Merck Index 1940). Note: Camphor oil is separated into four distinct essential oil types by fractional distillation. White camphor oil does not contain safrole and is the type normally sold as ‘camphor oil’ for use in aromatherapy. Toxicological concerns regarding safrole have limited the general use of the other forms of camphor oil (Tisserand & Balacs 1995). Note: See Volume 1 for a discussion on safrole toxicology. Caraway oil: primarily carvone and limonene, small amounts dihydrocarvone, carveol, dihydrocarveol (Evans 2002). Attributes: carminative and antispasmodic Uses: • Aromatic carminative; a component of purgative pills to allay the tendency to gripe; administered on sugar to relieve flatulent colic (BPC 1934). • Caraway Water (Aqua Cari) used in treatment of flatulence and is a suitable vehicle for children’s medicines (BPC 1968; BPC 1934). Cardamomum oil: primary components are terpinyl acetate, cineole. Cardamom tincture (prepared from seeds): this is the main form used in pharmacy Attributes: carminative properties Use: •  Compound Cardamomum tincture: cardamom seed 1.4%, Caraway, cinnamon, cochineal, alcohol (60%) (BPC 1968). Oil of Cinnamon: cinnamic aldehyde (60–75%); phenols mainly eugenol (4-10%), plus small amounts pinene, phellandrene, caryophyllene, etc (Evans 2002). Attributes: mild astringent, carminative, powerful germicide (Evans 2002). Uses: • In capsules, on sugar or as Spiritus Cinnamomi for common colds and influenza. Oil inhaled for phthisis and used as a spray in catarrh. Also employed in preparation of lozenges and pastilles (BPC 1934). • Aromatic carminative for use internally to treat colic (Merck Index 1940). Clove oil: eugenol (84–95%, incl. 3% acetyleugenol), ɑ- & β-caryophyllenes (at least 28 compounds reported) (Evans 2002). Attributes: carminative; useful preservative; external use as liniment with irritant, rubefacient, slight analgesic properties (BPC 1968). Uses: • Clove oil employed in dentistry; local analgesic effect, do not use excessively as it can cause damage to the gums (gingival tissue) (BPC 1968). • Oil is antiseptic and anti-putrescent; internal use as antispasmodic and carminative; used in phthisis and to reduce expectoration in coughs; applied locally to tooth cavity as antiseptic and analgesic (BPC 1934). Carminative for flatulent colic and with purgatives to prevent griping (Merck Index 1940). • External use: mixed with olive oil (2 parts) and applied to neuralgic areas; employed as embrocation for bronchitis, whooping cough and rheumatism (BPC 1934). Coriander oil: linalool (coriandrol: 65–70%), smaller amounts of ɑ-pinene, y-terpinene, limonene, p-cymene (over 40 constituents isolated) (Evans 2002). Attributes: carminative Use: • Added to purgatives to prevent griping (BPC 1968; Merck Index 1940; BPC 1934) Dill oil: primarily carvone (43–63%) and limonene. Other components dillapiole, myristicin (Evans 2002). Attributes: carminative Use: • Important component of infant gripe water for treatment of flatulence; useful vehicle for children’s medicines (BPC 1968; Merck Index 1940; BPC 1934).

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Eucalyptus (Eucalyptus globulus and other species)

Fennel (Foeniculum vulgare)

Ginger (Zingiber officinale)

Lemon (Citrus limon)

Nutmeg (Myristica fragrans)

Orange (Citrus aurantium)

Eucalyptus oil: at least 70% cineole. Attributes: decongestant, antiseptic Use: • Coughs, ENT (ear, nose and throat) infections and respiratory tract disorders (Evans 2002; BPC 1968). • Preparations: •  Used in mixtures, inhalations, lozenges, pastilles; external use as ointments and liniments (Evans 2002). • Internal use in subacute and chronic bronchitis; cystitis, urethritis; by inhalation as vapour off boiling water for asthma, subacute/chronic bronchitis, pulmonary gangrene, influenza. External use in skin disease; topical application or spray to mucous membrane of nose and throat (Merck Index 1940). • Used in bougies, suppositories and pessaries as an antiseptic and to disguise the smell of iodoform (BPC 1934). Fennel oil: trans-anethole (60%), fenchone (10–30) (Evans 2002). Attributes: carminative Use: • Aromatic carminative employed with purgative medicine to prevent gripe and as Aqua Foeniculi (Fennel Water) for intestinal colic of children (Merck Index 1940; BPC 1934). Note: Powdered fennel used as flavouring in Compound Liquorice Powder with senna and sulphur (BPC 1968). Oil of Ginger (contains over 50 components): β-phellandrene, camphene, cineole, citral, borneol, zingiberene, β-bisabolene, farnesene, β-sesquiphellandrene, curcumene, zingiberol (Evans 2002). Attributes: carminative, stimulant; strong antibacterial and antifungal properties for some rhizome components (Evans 2002). Uses: • Anti-nausea medication; ginger root often prepared as a tincture, which was employed for making syrup (BPC 1968). • Stomachic, carminative for dysentery, flatulent colic etc; in toothwashes, ginger beverages and liqueurs (Merck Index 1940). Oil of Lemon: limonene (94%), citral (3.4–3.6%), citronellal, geranyl acetate (1%) (Evans 2002). Use: • Terpeneless Lemon oil (obtained by removal of terpene components) extensively used as flavouring agent; has a strong lemon flavour and aroma and is more readily soluble than the natural oil (BPC 1968; BPC 1934). Nutmeg oil: pinene, sabinene and camphene (60–80%), dipentene (8%), myristicin (4%), elemicin and isoelemicin (2%), safrole (0.6%), alcohols (6%); and minor amounts of eugenol, methyleugenol, methoxyeugenol, isoeugenol (total 1%) (Evans 2002). Attributes: carminative Uses: • Mild counter-irritant effect used in liniments and ointments, e.g. for rheumatism; used in hair lotions. • Added to purgative pills to prevent gripe (Merck Index 1940; BPC 1934). Note: Large doses stimulate the cerebral cortex and may induce epileptic-type convulsions (BPC 1968). Orange oils: there are two limonene-based oil types with similar chemical components, i.e. Bitter Orange oil (Essence de Bigarde) and Sweet Orange oil (Essence de Portugal). Other components: citral, citronellal, methyl anthranilate (indeed, over 62 components from Libyan fresh orange peel have been identified) (Evans 2002). Citrus aurantium subsp. bergamia has stronger flavour and aroma, and is more readily soluble. Bitter Orange flower oil: methyl anthranilate (0.1–1% gives characteristic aroma), linalol (18–42%), limonene (9–19%), linalyl acetate (3–16%), trans-nerolidol (1–9%), geranyl acetate (1.5–4%), ɑ-terpineol (2–7%) (Evans 2002). Use: • Terpeneless orange oil (removal of terpene components) has stronger flavour and aroma, and is more readily soluble than Orange oil; used as a flavouring agent. • Other preparations: Orange-flower water, syrup of orange flowers. Caution: Bitter Orange oil has phototoxic attributes that are not present in Sweet Orange oil (Tisserand & Balacs 1995).

FLOWERS OF THE MATERIA MEDICA Peppermint (Mentha x piperita: hybrid between M. spicata and M. aquatica)

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Oil of Peppermint: menthol (30–55%), menthone (14–32%), cineole (3.5–14%), limonene (1–5%), menthofuran (1–9%), isomenthone (1.5–10%) and menthyl acetate (2.8–10%), plus carvone, pulegone and viridofloraJ164 l (Evans 2002). Japanese Peppermint oil (Mentha canadensis var. piperascens): 70–90% menthol (Evans 2002). Attributes: carminative, antispasmodic, mild antiseptic Uses: • Widely used in tablets and lozenges; flavouring in dental preparations (Evans 2002). • Oil of Peppermint is an aromatic stimulant and carminative. It relieves gastric and intestinal flatulence and colic, and is employed with purgatives to prevent griping (BPC 1934). • Relief of nausea: it has been shown that this oil diminishes gastric acidity and shortens the emptying time of the stomach (Merck Index 1940). • Oil acts as a local anaesthetic (BPC 1934). • Oil of Peppermint may be administered on sugar, or in mixtures (Peppermint Water, Spirit of Peppermint). Peppermint lozenges are a mild carminative with a pleasant taste. Oil of Peppermint is mildly antiseptic, used to flavour dental pastes, powders and washes (BPC 1934).

‘Aromatic waters’ from the British Pharmaceutical Codex, 1968.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Syrup of Ginger from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

During the latter part of the nineteenth century Eucalyptus oil gained international popularity and quickly entered into official pharmacopoeias across the world. The entry in the British Pharmaceutical Codex of 1934 is indicative, noting its value as an antiseptic and deodorant. It was regarded as being remedial for catarrhal inflammation of mucous membranes, especially of the respiratory tract and bladder. Pastilles containing the oil, often with menthol or red gum, were popular for head colds and sore throat. The oil, sprinkled on a handkerchief, was inhaled frequently for catarrhal colds and to prevent infection. An oil mixture with menthol, camphor or pine oil, was inhaled from a ‘dry’ inhaler as a decongestant. Steam-vaporised oil (sometimes with the addition of menthol, oil of pine and compound tincture of benzoin) was useful for cough relief in chronic bronchitis and asthma. Oily spray solutions and ointments for treating catarrh (mucous congestion) were prepared with eucalyptus and pine oils and other ingredients such as cocaine, menthol and/or camphor. In addition, a Eucalypt-based ointment (the oil mixed in soft paraffin) was employed for the treatment of burns and as a mild antiseptic dressing (BPC 1934).

 Ginger essential oil. (Courtesy Mountain Rose Herbs)

Eucalyptus drops. (Courtesy Felton Grimwade & Bosisto’s Pty Ltd)

Eucalyptus oil. (Courtesy Felton Grimwade & Bosisto’s Pty Ltd)

Food, water and shelter are the primary imperatives in establishing any new settlement – and the vegetable garden ranked high on the list of necessities in any pioneering venture. However, along with this type of garden many common ornamentals (and weeds) found their way into cultivation. The Asteraceae (Daisy) family would have been foremost among these plants – as they continue to be today. Numerous native species in this genus also have substantial therapeutic potential. The favourite medicinal herbs that were readily established included Marigolds, Chamomiles, Dandelion and various daisies. These plants were of significant value in a land where household remedies were usually the mainstay of medical care. Their therapeutic promise continues to expand their potential uses to this day – exceptional remedies with an equally exceptional future.

Chapter 2

ASTERACEAE: DAISIES OF THE APOTHECARY

Homoeopathic medicine kit. In many Australian households the mother took on the general doctoring, which could include the use of homoeopathic remedies. Homoeopathic medicine kits contained a fairly standard set of remedies, with travelling sales representatives calling around a couple of times a year to replenish used stock. Among the most common contents would be: Aconite for fevers; Arnica for injuries; Apis for fluid retention (swellings), insect bites or stings; Bellis for bruising; Nux vomica for nausea and ‘overindulgence’ (including hangovers); Camphora for collapse; Urtica for itching; and Sulphur for skin problems. (Image courtesy Martin & Pleasance, Port Melbourne)

The Garden Apothecary

The gardens of the early colonists had far more practical value than we can possibly imagine. They were not merely a culinary resource for herbs and spices. Many women used a basic first-aid kit and were very familiar with herbal remedies. There is where the conventional cottage garden became important. Common remedies acquired a special value in country regions, where there was usually a dearth of medical expertise. Indeed, even a few indigenous plants gained a measure of popularity. With a scarcity of medical supplies the cultivation of household remedies, where possible, was essential – and a surprising number were sourced from annual flowering plants.

The old and the new – wildflower gardens at the Chelsea Botanic Gardens, London (top), and the Brisbane Botanic Gardens. The Australian bush provides quite a different backdrop for wildflowers in comparison to the plants commonly found in European gardens – albeit many common medicinal herbs were imported and flourished in the ‘Great South Land’. 47

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Thus common remedies were by no means undervalued. The aromatic mints1, gingers, orange and lemon were favourites. While wound-healing herbs for treating infections and fractures predominated, small weedy plants such as the Dandelion and Chicory were premier liver tonics. Healing remedies from the Daisy family (Asteraceae) attracted particular interest, with some tried-and-tested herbs rating enough credit for inclusion in the official pharmacopoeias. Comfrey, the Common Daisy and Calendula provided household ‘wound-worts’ and antiseptics of inestimable value. The soothing effect of Chamomile was equally indispensable for irritable, teething babies, or as a carminative for stomach dysfunction. Indeed, many aromatic remedies that had flavouring qualities were familiar carminative agents. Australian Bush Flower Essences, developed by Ian White from native bush flowers, have a similar basis to the Bach Flower Remedies. There are 50 basic remedies – all of which have specific emotional indications for their use. (Image courtesy Australian Bush Flower Essences)

Rescue Remedy products. In the 1930s the Bach Flower Remedies were developed in England for the treatment of stress and emotional disorders. While very similar to homoeopathic medicines in that the flower essence is highly diluted, they differ somewhat in philosophy and preparation. Edward Bach believed that the dew collected from flowers contained various psychic properties of the plant, which were more potent when collected from blossoms grown in the sun. The flowers could be steeped in a bowl of sunlit water to prepare the remedy and preserved with brandy. One of the most famous of these remedies has been Rescue Remedy, for acute injuries and emotional trauma. (Image courtesy Martin & Pleasance, Port Melbourne)

It is important to note that numerous ordinary herbs were recognised medicines in professional circles. It should come as no surprise to find that many are still in use today – a lasting testimonial to their 1 Numerous herbal remedies with essential oil components are discussed in substantial detail in Volumes 1 and 2.

significant therapeutic value. Indeed, over the last few decades research efforts have not only validated their efficacy, but their potential has been expanded upon – giving many herbs a ‘new life’ in modern therapies. In addition, a few native remedies came into common use. Some of these had already carved out an established role in other traditions, particularly native species with close Asian relatives. They included an analgesic ‘Daisy Cress’ that was highly effective for easing toothache – as well as a few worthy relatives with antimicrobial, anti-inflammatory and woundhealing properties. These herbs did not escape the vigilant evaluation of the native flora in the search for medicines.

A Wound-wort of Distinction: Bellis perennis

The considerable reputation of the humble daisy as a healing herb has been largely forgotten today. Nicholas Culpeper (1653) held daisies in extremely high regard: The herb is under the sign Cancer, and under the dominion of Venus, and therefore good for wounds in the breast, and very fitting to be kept both in oils, ointments, plasters, and syrup. The greater wild daisy [Chrysanthemum leucanthemum] is a wound herb of great

ASTERACEAE: DAISIES OF THE APOTHECARY

Calendula flowers. The Daisy family (Asteraceae) has provided a remarkable number of exceptionally effective herbal medicines, albeit many remain underappreciated. While the scope of their medicinal recommendations could fill a volume such as this on its own, a few outstanding remedies with an ancient history of use deserve special mention. Their enduring role has seen them utilised in Australian herbal traditions since the arrival of the First Fleet, seeds of ancient medical traditions that migrated from Europe with the early settlers. (Image courtesy Berdan, Wikimedia Commons, CC-by-SA 3.0 Unported)

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Bellis perennis is widely naturalised throughout the southeastern part of Australia, ranging from southern New South Wales, to Victoria, adjacent regions of South Australia, and Tasmania. respect often used in those drinks and salves that are for wounds, either inward or outward. The juice or distilled water of these, or the small daisy [Bellis perennis], reduces the heat of choler, and refreshes the liver and other inward parts. A decoction made of them and drunk, cures wounds of the breast: also cureth ulcers and pustules in the mouth or tongue, or in the secret parts [genitals]. The leaves bruised and applied to the testicles or any other part that is swollen and hot, reduces the heat. A decoction made thereof, with wall-wort and agrimony, and placed fomented or bathed therewith warm, giveth great ease in palsy, sciatica, or the gout. The same also cures knots or kernels in any part of the body, and bruises and hurts that come of falls and blows; they are used successfully for ruptures and inward bruisings. An ointment made thereof heals all wounds that have inflammations about them, or by reason of running are kept long from healing. The juice of them dropped into the running eyes of any, cures them. As a poultice for sores they are good.

Bellis perennis, from Johann Georg Sturm, Deutschlands Flora in Abbildungen, 1795.

John Gerarde (1597) also recommended Bellis perennis for feverish conditions: ‘The decoction of the field Daisie (which is the best for physicks use) made in water and drunke, is good against agues’. Its analgesic attributes were held in equally high repute: ‘The

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Daisies do mitigate all kinde of paines, but especially in the joints, and gout, if they be stamped with new butter unsalted, and applied upon the pained place: but they worke more effectually if Mallowes be added thereto. The juice of the leaves and roots snift up into the nostrils, purgeth the head mightily, and helpeth the megrim [headache/migraine].’ The latter sounds very similar to the use of the native Australian Sneezewort (Centipeda cunninghamii). It is rather remarkable that the therapeutic reputation of this unassuming little herb seems to have arrived intact in more modern times. Indeed, some of the old recommendations appear as valid today as when they were written. The physician Dr Dorothy Shepherd held the daisy in equally high esteem: So the little Common Daisy on the green lawn is a valuable wound wort and a precious jewel in the crown of health we should all wear. A kind of Providence has planted it, where it is most needed, in the meadows near the country lanes, for the use of country men and women, for travellers, tourists, harvesters and soldiers on the march, who so heedlessly stamp on it in their daily round of toil. How often do we not overlook the little things which are meant for our good, and rush after some distant unobtainable chimera instead! (Shepherd 1969).

The use of Bellis perennis continues in homoeopathic traditions as a potent wound-healing ‘bruisewort’ with analgesic properties. Its main indications are for the treatment of weakness and the ‘bruised’ soreness that follows episodes of rheumatic pain, gout or general injuries – particularly where the symptoms are associated with exposure to cold.2 Bellis has been widely used for treating tumorous growths, especially those that develop following an injury. Additionally, the remedy has been useful for prolapsed conditions such as haemorrhoids or laxity of the uterine muscles, and has been considered a specific for the treatment of uterine congestion and enlargement. It continues to be utilised by many homoeopaths for this purpose and has often been recommended to deal with deep tissue injuries, including the side-effects of pelvic and breast surgery. Various investigations of the phytochemistry of Bellis perennis support its traditional use. The herb contains flavonol glycosides, phenolic acids, triterpenoid saponins and an essential oil. The antioxidant activity of 2 Edward Pollock Anshutz (1983) provides an excellent in-depth review of the homoeopathic use of this herb in New, Old and Forgotten Remedies (Narayana Publishers, Germany).

flower extracts was linked to its phenolic components, notably flavonol glycosides (Kavalcioğlu 2010; Siatka & Kasparova 2010). Interestingly, in Czech traditions Bellis has been utilised as an expectorant agent, as well as having diuretic, anti-inflammatory and vulnerary (woundhealing) properties, which has been largely attributed to its saponin components (Siatka & Kasparova 2010, 2003). Bellis perennis also has good antimicrobial potential. The essential oil components are antibacterial – as well as showing antimycotic (antifungal) activity against species of Trichophyton, Microsporum, Candida and Aspergillus niger, which was associated with a saponin complex (containing bellissaponins). Polygalacic acid glycoside components also possess activity against Candida and Cryptococcus yeasts (Kavalcioğlu 2010; Gudej & Nazaruk 2001; Avato 1997; Willigmann 1992; Bader 1990; Desevedavy 1989). Recently, saponin-based flower extracts have attracted interest as anti-cholesterol agents, showing an inhibitory effect on triglyceride levels. In addition, triterpene saponins (perennisosides) have anti-obesity potential (Morikawa 2011, 2010, 2008; Yoshikawa 2008). Studies have also suggested cosmetic uses for the common daisy. Extracts with a ‘skin-lightening’ property due to their effect on melanin biosynthesis have been proposed for use in hyperpigmentation disorders such as ‘age spots’ (John 2009; www.incosmeticsasia.com).

Comfrey: An Ancient Wound Healer Comfrey is an ancient herbal remedy with excellent wound-healing properties. Culpeper valued it highly:



The root being outwardly applied, cures fresh wounds or cuts immediately, being bruised and laid thereto: and is special good for ruptures and broken bones; so powerful to consolidate and knit together, that if they be boiled with dissevered pieces of flesh in a pot, it will join them together again. It is good for women’s sore breasts; also to repress profuse bleeding of the haemorrhoids, or piles, to cool the inflammation of the parts thereabouts, and to ease pain. The roots of comfrey taken fresh, beaten small, and spread upon leather, and laid upon any place troubled with the gout, presently gives ease; and applied in the samemanner it eases pained joints, and tends to heal running ulcers, gangrenes, mortifications, for which it hath by often experience been found helpful.

ASTERACEAE: DAISIES OF THE APOTHECARY

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Symphytum, syn. Comfrey root, Martindale Extra Pharmacopoeia, 1941. Symphyti Radix, Common comfrey root, Peter Squires, Companion to the latest edition of the British Pharmacopoeia, London, 1899.

Comfrey cream. (Courtesy Martin & Pleasance, Port Melbourne)

infections. The herb has even shown positive results for alleviating the pain associated with osteoporosis. Its healing effects are attributed to allantoin, which acts to promote granulation and tissue regeneration. It also contains a fair amount of mucilage, which has a demulcent effect, with polysaccharide components showing immunosupportive, anti-inflammatory and healing properties. Rosmarinic acid in the herb is also of value, showing anti-inflammatory, antioxidant and antimicrobial activity. Unfortunately, Comfrey also contains pyrrolizidine alkaloids (0.03%3) with detrimental potential – hepatotoxic, carcinogenic and mutagenic activity (PDR Herbal Medicines 2004; van Wyk & Wink 2004). It is therefore no longer recommended for internal use, or in cases where broken skin would allow greater absorption of the cream. 3 Not all pyrrolizidine alkaloids are toxic, and there can be substantial variability in the levels that are present in the herb. This means Comfrey’s harmful potential can vary significantly.

Analgesic Daisies Spilanthes and Acmella

Symphytum officinalis herb.

Although Culpeper possibly overstates its boneknitting attributes, Comfrey continues to be highly valued for injuries, although antibiotics would probably be more appropriate for serious

Acmella oleracea. (Courtesy Jeevan Jose)

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Northern Territory and Queensland to northern New South Wales – and var. brachyglossa extends to Papua New Guinea. • Spilanthes acmella is now placed in the closely related Queensland genus Blainvillea. • Blainvillea contains a couple of other native species, among them B. dubia, which is native to Far North Queensland; B. gayana4 is a tropical West African weed that has been found on the central Queensland coast. 4 In Senegal, Africa, this herb, despite its toxic reputation, was utilised medicinally – a decoction of the leafy stems or the powdered seeds as an antiseptic useful for eye problems (Burkill 1985).

Acmella grandiflora. (Courtesy Russell Cumming)

The Asteraceae family is prolific. It contains an extremely large number of genera (around 1650– 1700), of which some 300 are represented in Australia, albeit many of the species found here are imported ornamentals and weeds. A large number of Australian Daisies are very similar to those found overseas. This has made their botanical classification somewhat confusing – a situation compounded over time by the numerous weedy escapees. The identification of these plants can be quite difficult and those mentioned in the older literature were often placed in different genera to their classification today. The genus Acmella, although it contains only around 30 species, is widespread (the Americas, Australasia and the Pacific) with a couple of species introduced into Australia. Acmella oleracea (formerly classified as Spilanthes acmella or S. oleracea) is one of the more familiar medicinal herbs. Various native species from northern Queensland, which were formerly classified as Spilanthes, are now considered to belong to Acmella or Blainvillea: • Acmella grandiflora (including the varieties var. brachyglossa, var. discoidea and var. grandiflora), A. paniculata and A. uliginosa are found in Australia. • Acmella grandiflora has the most widespread distribution, from Western Australia, the

The wild Daisy Cress, Acmella grandiflora (syn. Spilanthes grandiflora), is a creeping tropical herb. Aboriginal people adopted the practice of chewing the roots without swallowing them as a toothache remedy on the Palmer goldfields in north Queensland – a custom thought to have been acquired from the Chinese immigrants (Webb 1959). Numerous closely related species had similar uses, including the flowers of the South African Spilanthes mauritiana, utilised as a toothache remedy by the Xhosa and Zulu. The remedy was reported to cause a tingling and numbness of the mouth for about 20 minutes – after which the toothache disappeared and did not recur. The herb was also recommended as an anti-rheumatic, as a treatment for headaches (the flower and fruiting top rubbed on the forehead), and as a snake-bite remedy (Watt & Breyer-Brandjwijk 1962). The widespread use of various Acmella and Spilanthes species for toothache is linked to the presence of a potent local analgesic substance (spilanthol, an alkylamide5) in the flowers. Spilanthol was originally found to be a difficult substance to extract due to its chemical instability – which may account Spilanthes mauritiana. for the variable activity (Courtesy Bart Wursten)

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of herbal extracts, suggesting that the fresh plant would have been among the most effective forms to use. Spilanthol has an efficient numbing (analgesic) effect, as well as anti-inflammatory and antimicrobial properties. This makes it well suited for use in the treatment of painful conditions such as trauma, tendinitis and insect bites (Zakaria & Mohd 1994; Carle 1990a; Oliver-Bever 1986). Spilanthes and Acmella have provided highly useful febrifugal agents. In Papua New Guinea Spilanthes paniculata was a bath ingredient that helped to reduce the early symptoms of malarial fevers. The herb was taken to ease body pains, as well as for the relief of stomach-ache (Holdsworth & Mahana 1983). Evaluation of an antimalarial herbal medicine composed of Cassia occidentalis, Lippia chevalieri and Spilanthes oleracea showed that the last named, the Brazilian Cress, made a valuable contribution to its efficacy (Gasquet 1993). The closely related Beach Sunflower (Wedelia biflora) has been widely used in Southeast Asia as a leaf decoction for relieving periodic fevers and as an anti-malarial remedy (Perry & Metzger 1980). Indian medical traditions valued Spilanthes acmella for a great variety of conditions: bladder and kidney afflictions (including kidney stones), leucorrhoea (white vaginal discharge), scurvy, supression of menses (amenorrhoea), mouth sores, and paralysis of the tongue. The latter may have been due to its pungency – an attribute that inspired its use in places as diverse as Africa and India to induce salivation and ease mouth Spilanthes paniculata. (Courtesy JIRCAS, www. jircas.affrc.go.jp) (Below) Spilanthes acmella. (Courtesy Tim McCormack via CC-by-SA)

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soreness (Watt & Breyer-Brandjwijk 1962; Chopra 1956). Interestingly, Brazilian healers recommended the leaf and flower (infusion or decoction) similarly – for treating stomatitis, throat complaints, toothache and as a remedy for stammering (Holetz 2002). The herb was also reputed to have haemostatic properties (Oliver-Bever 1986). Spilanthol can readily permeate the buccal (oral cavity) mucosa and skin surfaces, which indicates good bioavailability and explains the fairly rapid efficacy of the remedy (Boonen 2010a, 2010b). In addition, Spilanthes acmella has been widely valued as a healing agent, with the leaf juice and bruised leaves applied locally to wounds or ulceration. The root infusion was a useful anti-inflammatory to ease the discomfort of psoriasis and other itching (pruritic) skin disorders – although it was noted to have purgative potential if taken internally (Quisumbing 1951). In the Philippines similar recommendations mention the use of Spilanthes acmella as a diuretic and solvent for renal calculi – and investigations have shown leaf extracts (alcohol-based) had diuretic properties similar to the conventional drug frusemide.6 Flower extracts have also demonstrated good diuretic properties. This is of interest because diuretics can have a useful antihypertensive effect – which is further supported by investigations showing that herb extracts (from aerial parts) possessed vasorelaxant (vasodilation) and antioxidant attributes (Yadav 2011; Wongsawatkul 2008; Ratnasooriya 2004). In India the herb even had a reputation as a tonic aphrodisiac that was said to be particularly valuable for sexual performance problems that occur with ageing. This effect was possibly linked to its alkylamide components (Sharma 2011). Modern research has tended to support many more of the traditional uses of these herbs (see Table 2.17).

5 Spilanthol is the most prevalent component of pharmacological interest, although other alkylamides are present in the herb (Boonen 2010a). See Prachayasittikul (2009) for further details of other bioactive metabolites. 6 Frusemide is primarily utilised in the treatment of hypertension, oedema and congestive heart failure (the latter being associated with significant oedema). Because the use of diuretics can result in low potassium levels (hypokalaemia), this has led to the development of combination products that incorporate this mineral. 7 For the sake of completeness, and to truly appreciate the enormous value of medicinal Asteraceae, herbs that have an established role in herbal medicine, i.e. Arnica, Calendula and Bellis, are outlined separately in the text.

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  Kaurenoic Acid

Wedelia paludosa. (Courtesy Eduarda Mendes, flickr)

Kaurenoic acid and derivatives have shown interesting antifungal activity against Botrytis cinerea (Cotoras 2004). This is the fungus (appearing as dark brown balls in this image) that is utilised in wine making, although it can also cause significant grape crop losses under the wrong conditions. (Image courtesy Ninjatacoshell, Wikimedia Commons via CC-by-SA 3.0 Unported)

Kaurenoic acid is an active antimicrobial component that is present in many Wedelia species, including W. paludosa and W. trilobata – as well as a number of other genera, among them Annona, Xylopia and Aralia. It has demonstrated antibacterial properties against Bacillus cereus and Escherichia coli (Wilkens 2002) and Staphylococcus aureus (Okoye 2012) – as well as good activity against the oral (dental) bacteria Streptococcus mutans (de Andrade 2011). Kaurenoic acid and luteolin from the flowers of Wedelia paludosa (syn. Acmella brasiliensis) have shown antifungal properties against dermatophytes (Trichophyton and Epidermophyton spp.), which suggests The

potential for the treatment of skin infections (Bresciani 2004; Cechinel Filho 2004; Mottakin 2004; Sartori 2003; Block 1998b). anti-inflammatory and analgesic properties of kaurenoic acid are equally significant. Indeed, the activity of kaurenoic acid and luteolin was more potent than a number of standard analgesic drugs: acetyl salicylic acid (aspirin), acetaminophen, dipyrone and indomethacin (Block 1998a, 1998b). Kaurenoic acid therefore has potential as an anti-inflammatory topical application for skin disorders (Choi 2011; Boller 2010; Lim 2009), as a treatment for colitis (Paiva 2009) – and as an anti-asthmatic agent due to its significant antispasmodic properties (Hipolito 2011; Cho 2010; de Alencar Cunha 2003). There are a few other studies that suggest kaurenoic acid possesses vasorelaxant properties with antihypertensive potential (Tirapelli 2005, 2004, 2002; Ambrosio 2004); hormonal effects (a potent stimulatory effect on uterine contractions; Meena 2011) and anticancer (antiproliferative, cytotoxic and antitumour) activity. Various derivatives are under investigation for the development of specific anticancer products (Cuca 2011; Peria 2010; Cavalcanti 2009; Costa-Lotufo 2002). Brazilian studies of the antidiabetic potential of Wedelia paludosa extracts identified kaurenoic acid as one of the active hypoglycaemic compounds (Bresciani 2004; Novaes 2001). Furthermore, kaurenoic acid and some derivatives have shown antiparasitic activity against Leishmania (syn. Viannia) braziliensis (Brito 2006), Trypanosoma cruzi (Batista 2010, 2007, 1999) – and molluscicidal effects on the snail vector Biomphalaria peregrina involved in the transmission of schistosomiasis (Bardon 2007). Kaurenoic acid is present in substantial quantities (66 mg/fresh fruit) in the Cherimolia (Annona cherimolia) (Guillope 2011). It can also accumulate in the bark of Annona glabra (with small quantities in the leaves) (Oleviera 2002) and root bark of A. senegalensis (Okoye 2012) – which suggests that this compound is likely to be present in other Annona species such as the wonderfully sweet-flavoured Atemoya.

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sealant within honeybee hives. Sourced from the local flora, this soft, malleable substance usually has substantial antibacterial properties. While many medicinal claims have been made for propolis, its value can vary – depending upon the floral source. This would suggest that propolis sourced from Australian native beehives could have similar interesting chemical components, particularly if the product is harvested from areas where Wedelia herbs predominate.

Custard Apple or Atemoya (Annona squamosa x A. cherimolia).

Diterpenoids isolated from propolis sourced from the Brazilian Stingless Bee (Melipona quadrifasciata anthidioides) included kaurenoic acid, which displayed moderate antibacterial activity (Velikova 2000). Propolis is the resinous ‘glue’ that is employed as a structural

Australian Stingless Bees in hive. (Courtesy Russell & Janine Zabel)

Table 2.1 Summary of Investigations into ‘Daisy’ Herbs of Medicinal Value from the Genera Acmella, Spilanthes and Wedelia This brief overview summarises the main medicinal species utilised, with notations on the similar medicinal use of relatives (where applicable) – which may provide a valuable insight into the potential of related native Australian species. While the use of these herbs in Chinese and Indian traditions are included, this list is not exhaustive with regard to the use of these herbs in other countries. Category of activity and investigations Antimicrobial Spilanthes uliginosa (syns S. acmella, S. oleracea) • Extracts: demonstrated a wide range of antibacterial actions against Staphylococcus aureus, Salmonella typhi, Escherichia coli, Mycobacterium tuberculosis, Agrobacterium tumefaciens – as well as antifungal activity against Candida albicans, Trichophyton mentagrophytes and Aspergillus niger (Oliver-Bever 1986). • Extracts: good range of antibacterial activity, including activity against Corynebacterium diphtheriae and Bacillus subtilis (Prachayasittikul 2009). • Flower head extracts: good antifungal activity against agricultural pathogens (Fusarium oxysporum and F. moniliformis), as well as Aspergillus flavus, A. parasiticus (Rani & Murty 2006). • Antimicrobial attributes appear to be variable between the different species (and, possibly, different chemical races of the same plant). African samples of Spilanthes mauritiana showed only marginal antimycobacterial activity. However root and leaf extracts had antifungal potential against Aspergillus, although they were not active against Candida or Helicobacter pylori – a finding that highlights the ability of some plants to have a very specific activity against pathogenic organisms (Fabry 1998, 1996a, 1996b). • Extracts have shown antiviral activity (Oliver-Bever 1986). Root powder extracts have been utilised for treating HIV/AIDS and were reported to be very effective (Bajarang 2007).

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Spilanthes americana • Antibacterial activity against Staphylococcus aureus (Rojas 2006). Acmella (Spilanthes) calva • Antimicrobial (antibacterial, antifungal) activity: utilised for skin conditions, and has a rejuvenative reputation; decoction taken for dysentery in Bangladesh (Shanthi & Amudha 2010). • Extracts have antifungal activity against Fusarium oxysporum and Trichophyton mentagrophytes. Increased spilanthol content of extracts resulted in greater antifungal activity (Rai 2004). Spilanthes paniculata • Extracts showed good broad spectrum of activity against Salmonella paratyphi, Salmonella typhi, Vibrio parahemolyticus, Vibrio mimicus, Escherichia coli, Shigella dysenteriae, Pseudomonas aureus, Shigella boydii (Morshed 2011). Essential oil has specific antifungal activity against Microsporum gypseum (Trikunakornwong 1999). Wedelia chinensis • Leaf extracts possess highly effective wound-healing properties (Hegde 1994). • Extracts have demonstrated potent antibacterial properties against a range of bacteria: Staphylococcus aureus, Corynebacterium diphtheriae gravis, Streptococcus haemolyticus, Escherichia coli, Salmonella typhi (Duc Minh 1993). Wedelia biflora • The major component of the leaf oil extracted from the Beach Sunflower is α-pinene, a compound with antimicrobial properties (Cambie 1986). • Herb extracts: have shown antifungal properties against Rhizoctonia solani and Pythium ultimum (Miles 1990). Wedelia paludosa (syn. Acmella brasiliensis) • Good antifungal properties that appear to be linked to kaurenoic acid. Phytochemical investigations isolated kaurenoic acid, stigmasterol, oleanolic acid and a lactone (paludolactone) from fresh plant extracts. The kaurenoic acid content of the roots and stems could vary and was found to be higher during the autumn, which would therefore be the preferred time for harvest (Sartori 2003). Wedelia trilobata • Venezuelan studies: extracts showed an effective broad spectrum antibacterial action against gram-positive bacteria (Bacillus subtilis, Mycobacterium smegmatis, Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative bacteria (Proteus vulgaris, Pseudomonas aeruginosa, Salmonella group C, Salmonella paratyphi, Shigella sonnei). However, extracts did not show antifungal potential against Aspergillus flavus, Aspergillus niger, Mucor sp., Trichophyton rubrum or yeasts (Candida albicans, Candida tropicalis, Rhodotorula rubra) (Taddei & Rosas-Romero 1999).

Analgesic Spilanthes acmella (syns Acmella oleracea, Spilanthes oleracea) • Extracts possess significant local anaesthetic, analgesic and antipyretic activity (Ong 2010; Chakraborty 2010, 2004). Widely utilised in Southeast Asia (Malaysia and the Philippines) and India as a toothache remedy. • The genus has been recommended similarly in the medicinal practices of other countries: • Amazon: Spilanthes acmella, S. alba, S. ocymifolia (Schultes & Raffauf 1990). • Africa: S. mauritiana (Watt & Breyer-Brandwijk 1962). • Bangladesh: Spilanthes calva leaf and flowers used for toothache and as a local anaesthetic and analgesic remedy (Shanthi & Amudha 2010; Alam 1992). Wedelia biflora • Analgesic (antinociceptive) properties, along with W. trilobata and Eclipta alba (Sureshkumar 2007). Wedelia paludosa (syn. Acmella brasiliensis) • Kaurenoic acid and luteolin have shown potent antinociceptive activity (Block 1998a, 1998b). Wedelia chinensis • Leaf extracts: demonstrated substantial analgesic activity (Sureshkumar 2005).

Antidiabetic and metabolic potential Wedelia paludosa • Extracts were shown to lower blood glucose, with kaurenoic acid identified as one of the active hypoglycaemic compounds (Bresciani 2004; Novaes 2001).

Neurological activity Spilanthes acmella var. oleracea • Brazilian investigations revealed an interesting convulsive property of this plant; this resulted in its proposed use in experimental models of epilepsy (Moreira 1989). • S pilanthes acmella flower bud extracts had lipase-inhibitory properties with potential for development as an anti-obesity remedy for weight reduction. However, in this study Aframomum meleguetta seed extracts showed a much higher activity (Ekanem 2007). Wedelia chinensis • Plant extracts: potent anticonvulsant activity (Mishra 2011), as well as CNS depressant properties (Suresh 2010; Prakash 2008). Antioxidant properties of plant extracts, as well as anti-stress activity against brain neurotransmitters and enzyme MAO (monoamine oxidase) (Verma & Khosa 2009).

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Urinary tract disorders Spilanthes acmella • Flower extracts demonstrated strong diuretic effect that supports traditional use in Sri Lankan herbal medicine (Ratnasooriya 2004); leaf extracts have shown diuretic properties (Yadav 2011).

Immunological, antioxidant and anti-inflammatory activity Spilanthes acmella • Spilanthol and kaurenoic acid have significant anti-inflammatory activity (Wu 2008). • Extracts have good antioxidant properties (Prachayasittikul 2009; Wongsawatkul 2008), and significant anti-inflammatory and antipyretic activity (Chakraborty 2010, 2004). • Leaf extracts: substantial immunomodulatory (immune-supportive) activity (Rajesh 2011; Sayadi 2010). Acmella (Spilanthes) calva • Anti-inflammatory, antimicrobial (antibacterial, antifungal): tincture used to treat inflammatory jaw problems; popular use for skin disorders, strengthening effect on collagen and used in anti-wrinkle, anti-ageing skin formulations (Shanthi & Amudha 2010). • Whole plant extracts have also shown significant antioxidant potential, largely (94%) due to phenolic components, with carotenoids making a smaller contribution to its activity (Sikder 2010). • Extracts of the herb, which are added to chewing tobacco in India, have shown antimutagenic potential (Sukumaran & Kuttan 1995). Wedelia chinensis • Leaf extracts: anti-inflammatory activity comparable with aspirin and indomethacin (Sureshkumar 2005). Caffeic acid derivatives present in the herb, of which wedelosin has shown anti-inflammatory properties (Apers 2002). Wedelia (Sphagneticola) trilobata • Kaurenoic acid: analgesic (antinociceptive) and anti-inflammatory activity (Mizokami 2012). • Wound-healing and antibacterial activity of kaurenoic acid from leaf extracts (Balekar 2012).

Antiparasitic activity Spilanthes acmella • Extracts have shown good antimalarial activity with clinical potential (Gasquet 1993); antiplasmodial activity: N-alkylamides isolated as synergistic active components (Mbeunkui 2011). • Insecticidal activity against head lice (Pediculus humanus); flower extracts were the most effective (Ramdev 2011). • Plant extracts were anthelmintic against Hymenolepis nana and antiprotozoal against Entamoeba histolytica (Watt & Breyer Brandjwijk 1962). Spilanthes calva • Whole plant, flower heads: recommended in scabies treatments in Bangladesh (Alam 1992). • Affinin (spilanthol) shown to be the molluscicidal component of some Asteraceae herbs, i.e. Heliopsis longipes, Wedelia parviceps, Spilanthes oleracea (Johns 1982). Wedelia paludosa • Antiprotozoal activity against Trypanosoma cruzi, the organism responsible for Chagas disease (trypanosomiasis), could be linked to its kaurenoic acid content (Batista 2010, 2007, 1999). Wedelia trilobata • Kaurenoic acid has shown potent leishmanicidal activity against Leishmania braziliensis (Brito 2006). Wedelia subvaginata • Argentinian studies have shown herb extracts had molluscicidal effects on Biomphalaria peregrina (Bardon 2007).

Liver-protective (hepatoprotective) properties Spilanthes ciliata • Extracts gave significant protection against aflatoxin-induced liver damage (Shyamal 2010). Wedelia chinensis (syn. W. calendulacea) • Extracts have shown anti-hepatotoxic properties that protect the structural and functional integrity of the liver. Significant protective effects from liver damage due to paracetamol, D-galactosamine and carbon-tetrachloride toxicity. It has also shown experimental activity against hepatitis B. The herb had a substantial cholagogic effect and acted to strongly stimulate bile flow (Bhawna & Kumar 2010; Saleem 2010; Murugaian 2008; Emmanuel 2001; Lin 1994; Gopalakrishnan 1989; Sharma 1989; Yang 1987, 1986). Wedelia paludosa (syn. Acmella brasiliensis) • Significant protective effect of extracts on paracetamol-induced hepatotoxicity in mice (Meotti 2006).

Insecticidal, mosquitocidal and toxic potential Spilanthes acmella • Crushed plant and fruit used as insecticide and piscicide in India; flowers are powerful mosquito larvicide (Watt & BreyerBrandjwijk 1962; Chopra 1956). • Plant extracts: have shown excellent larvicidal activity against mosquito vectors for malaria and filariasis (Pandey & Agrawal 2009). Kaurenoic acid has larvicidal and trypanocidal activity (Haraguchi 2011; Block 1998a).

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• S  pilanthol (and some other components) has useful insecticidal properties that support the popular use of the Spilanthes genus against bedbugs and cockroaches (Watt & Breyer-Brandjwijk 1962). Spilanthes calva • Significant anti-feedant activity against Helopeltis theivora, a pest of the Tea plant, Camellia sinensis (Dolui & Debnath 2010). • Mosquito larvicide: Some species are very useful for killing mosquito larvae (larvicidal activity). Spilanthes acmella extracts (plant, flower bud) and spilanthol showed good activity against the vectors for filaria (Culex quinquefasciatus) and malaria (various Aedes species). Spilanthes calva and S. paniculata: also active as larvicides, albeit to a lesser extent (Ramdev 2011; Pandey 2011, 2007; Ramsewak 1999; Pitasawat 1998; Oliver-Bever 1986). • Piscicidal activity (fish poison): Spilanthes flower heads used to cause stupefaction of fish. West African tribes utilised Spilanthes mauritiana for this purpose. Experimentally, a volatile oil extracted from the plant was shown to be highly toxic to fish (Watt and Breyer-Brandjwijk 1962). • Leaf powder: used in Bangladesh as a fish poison with the addition of DDT (Alam 1992). This was found to be highly effective; DDT acted more slowly than spilanthol but its activity was five times more potent (Watt and Breyer-Brandjwijk 1962). Wedelia biflora • Stem and leaf extracts have shown anti-feedant activity against the Cotton boll weevil (Meena 2011; Miles 1990). • Anthelmintic activity for root extracts (Prakash Yoganandam 2009a). Wedelia chinensis • Insecticidal and insect-repellent activities (Baki 2005; Xian 2005, 2003; Pang 2000). Wedelia glauca • Oil has been evaluated against the honeybee mite, Varroa destructor, although Schinus molle had greater selectivity against the parasite (Ruffinengo 2005).

  Remarkable Arnica (Arnica montana)

Arnica cream. (Courtesy Arnica oil. (Courtesy Martin & Pleasance, Port Dr. Reckeweg & Co., Melbourne) Bensheim, Germany)

Of all the Asteraceae, there is one notable herb that rates highly for the treatment of traumatic injuries – the yellow-flowered Alpine Daisy, Arnica montana. This outstanding remedy has been used for centuries for trauma and bruising, and its effects can be dramatic. If employed immediately after an accident it reduces the tissue damage in a truly remarkable manner. However, in herbal medicine it is only used externally due to its irritant potential. The British Pharmaceutical Codex of 1934 recognised both the flower and root as official: ‘Arnica flower has an irritant effect upon the stomach and intestines.8 As a local application for sprains and bruises, where the skin is not too

Arnica montana, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

tender or broken, the tincture, Tinctura Arnicae Floris, has been employed.’ The Codex also noted: ‘The action of arnica rhizome is the same as that of the flower. The tincture, with or without dilution with water is a popular application for sprains 8 Taken internally, poisoning is associated with symptoms of severe gastroenteritis, nervous system distress (nervousness, irritability), accelerated heart rate and muscular weakness. Fatalities, albeit rare, have been recorded in the older literature.

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and bruises when the skin is unbroken. Liniment of arnica is applied with friction as a mild counterirritant, but cases of arnica dermatitis from the local application of arnica preparations have been reported.’ Although its use is to be avoided on open wounds, it can be applied around the injury site, as long as it is used only on non-broken areas of skin. However, Arnica has been extensively employed as a homoeopathic for internal use, having significant anti-shock and healing effects in cases of traumatic injury. Recently, clinical studies have suggested that it may also be useful as a topical application in osteoarthritis of the knee (Knuesel 2002). There are some additional

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interesting investigations of the herb that found extracts (particularly the phenolic components) had a detoxicant effect on liver function. Polysaccharides with immunomodulatory properties were isolated, as well as a number of cytotoxic sesquiterpenes, including helenalin (Iamemii 1998; Iaremii 1998; Woerdenbag 1994; Puhlmann 1991; Marchishin 1983). Helenalin is of particular interest as an anti-inflammatory and anti-tumour component, with antibacterial, anti-trypanosomal and anti-plasmodial activity – however, it is also highly toxic (Boulanger 2007; Huang 2005; Jimenez-Ortiz 2005; Francois & Passreiter 2004; Schmidt 2002; Lyss 1998; Powis 1994; Chapman 1988). Extracts were also active against dental bacteria – although their effectiveness could vary (Iauk 2003; Koo 2000).

Beach Sunflowers and Singapore Daisies

Wedelia asperrima. (Courtesy Russell Cumming)

Arnica, from Peter Squires, Companion to the latest edition of the British Pharmacopoeia, 1899.

Wedelia is another genus in the ‘daisy’ classification that is closely related to Spilanthes and Acmella – and a number of species are Australian natives: • Wedelia asperrima, the Sunflower Daisy: found throughout the northern tropics, ranging from the coast to inland sites – Western Australia (northwest), Northern Territory, northern Queensland. • Wedelia longipes: Northern Territory and northern Queensland (Cairns, Cape York). • Wedelia spilanthoides: found throughout much of Queensland, ranging from the tropics to northern New South Wales – also has limited distribution in the Northern Territory and extends to Papua New Guinea.

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• Wedelia biflora (recently reclassified as Melanthera biflora, syn. Wollastonia biflora), the Beach Sunflower, has a similar distribution to Wedelia spilanthoides. Beach Sunflower is common along the Queensland coastline, ranging to northern New South Wales. It is also found in the Northern Territory – as well as Oceania and Southeast Asia. • Wedelia stirlingii, W. urticifolia and W. verbesinoides: these three species are native to Western Australia and the Northern Territory9, with W. stirlingii extending its range to South Australia and Queensland. • Wedelia trilobata (now Sphagneticola trilobata)10, the Singapore Daisy: considered to be a major pest along the Queensland coastline, extending into the Northern Territory and tropical Western Australia. The herb originates from Central and South America (Mexico to Argentina).

Melanthera integrifolia, flower detail and coastal habitat. (Images courtesy Kim & Forest Starr, Hawaii)

The Beach Sunflower (Melanthera biflora syn. Wollastonia biflora, formerly Wedelia biflora) is a native Sunflower found along the east coast of Australia that ranges to the Indo-Pacific region and would appear to be suitable for coastal revegetation projects. Indeed,

the closely related Hawaiian Melanthera integrifolia is a heat, salt and wind tolerant species that has been utilised for erosion control, and as a long-lived groundcover that does not have invasive tendencies.

Beach Sunflower (Melanthera biflora). (Image on right courtesy Russell Cumming) 9 There are also a couple of, as yet, unnamed species from WA (sp. Hamersley) and the NT (sp. Limestone). 10 Most of the literature will be found under Wedelia trilobata.

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The Beach Sun-flower has attracted little attention in Australia as a medicinal plant, although it does have a good reputation as a wound-healing herb overseas. The leaf poultice, or the juice squeezed from the leaves, was easily applied to sores, wounds, insect bites, swellings, scabies and numerous festering forms of skin problems (Perry & Metzger 1980). In Tonga the leaf juice (extracted by pounding the leaves between hot stones) was applied to serious wounds, including injuries contaminated by the tetanus bacterium (Cribb & Cribb 1985; Weiner 1985). The leaves were combined with ginger for treating venereal disease in Singapore. The fresh roots (decocted) provided a traditional medicine in the Philippines for gynaecological disorders, being utilised as an emmenagogue, for leucorrhoea, and other infections.11 It was also taken to ease stomachache, and as a diuretic. While the roots had a slight purgative action, the use of the flowers was avoided as their action was said to be much more drastic (Perry & Metzger 1980; Quisumbing 1951; Burkill 1935). Fijian medicine has utilised the Beach Sunflower in an equally diverse manner. The liquid pressed out of the young leaf buds was taken to ease ‘pains in stomach’ and nausea (Weiner 1985). The leaf decoction provided a remedy for bacillary dysentery, hepatitis, haemorrhoids and bladder infections. The herb was incorporated into treatments for appendicitis, eczema, muscular spasms, convulsions, stomach-ache and fish poisoning. Leaves soaked in coconut oil provided a liniment for massaging sprained or bruised limbs (Cambie 1986). Somewhat more unusual was the recommendation that a liquid (pressed from the leaves) was useful for testicles swollen due to ‘cold’ and diarrhoea. To encourage urination, or for the relief of testicular swelling associated with herniation, the liquid from the stem was used (Weiner 1985). The Beach Sunflower has had a similarly varied and indispensable medicinal role throughout Papua New Guinea. The leaf or stem was used to make remedies (usually a water-based drink) for diarrhoea, dysentery and stomach-ache – or to allay coughing problems (leaf infusion). In the Central Province and Manus the leaf or stem sap was applied to bleeding cuts to encourage blood clotting and form a protective scab. In Madang 11 Some of these uses may be linked to the antibacterial and uterine stimulant effects of kaurenoic acid.

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Province sap from the heated leaves was dripped onto tropical sores, or rubbed onto scabies infections. In Morobe Province the fresh leaf sap was applied to centipede bites. Additionally, the leaves provided a useful warm compress for general pain relief. In New Britain (Buka Island) an infusion (the leaves crushed and mixed with seawater) was taken for malarial fevers. The leaves were also a popular analgesic to ease headache or toothache pain (Woodley 1991; Holdsworth 1984; Holdsworth & Lacanienta 1981).

Sunflower Daisy (Wedelia asperrima). (Courtesy Russell Cumming)

The Sunflower Daisy (Wedelia asperrima) is very similar in appearance to the Daisy Cress (Acmella grandiflora) – although Sunflower Daisy leaves have a softer texture and the shape of the flower head differs somewhat. While the Daisy Cress is nontoxic, Sunflower Daisy is a known stock poison – albeit animals generally find the plant highly unpalatable and will not eat it unless desperate. It contains a chemical called wedeloside that acts to block the cellular use of oxygen, resulting in cell death. In particular, it disrupts liver function. In sheep and cattle, poisoning occurs within 24 hours of eating it and, although the symptoms may not be apparent until 18 hours after ingestion, when they manifest death generally occurs within 30 minutes (Dowling & McKenzie 1993; Lewis 1981; Everist 1981). In South America, studies have also implicated Wedelia glauca (now Pascalia glauca) as a stock poison (Tapia 1996; Collazo & Riet-Correa 1996).

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Singapore Daisy: A Problematic Groundcover

Singapore Daisy

The Singapore Daisy (Wedelia trilobata, now Sphagneticola trilobata) has been somewhat misguidedly introduced around the world as a golden-flowered groundcover. In many regions it has subsequently achieved serious pest status and is almost impossible to eradicate. The weed has a particularly invasive reputation in the Australian tropics. The plant, which tends to persist despite the use of herbicides or manual extraction, has a very quick growth habit, particularly under hot, humid conditions. It rapidly forms a thick carpet over the ground and, while this may be a blessing for preventing weedy invasions in the urban garden, in the tropical forest it quickly becomes an insurmountable barrier to seedling growth. The fact that the weed can readily spread to remote sites during the wet season floods adds to its invasive potential. In Central America and the Caribbean, the herb has been utilised as a remedy for the treatment of sores, swelling, stubborn non-healing wounds and painful arthritic disorders (Balekar 2012). In Belize it had a medicinal reputation similar to various other Wedelia species: for the treatment of hepatitis, indigestion due to sluggish liver, white stools, urination problems (dysuria, anuria) and infections. Externally, the wash or bath was considered useful for muscle cramps, and rheumatic pain or swellings. The fresh leaves were also poulticed locally for the relief of arthritic pain (Arvigo & Balick 1993). The leaf tea has been used as a cold and flu remedy, or poulticed on skin problems such as sores. Furthermore, it has a reputation for use in gynaecological (menstrual) disorders, abortion and to clear the placenta following birth (Meena 2011). Certainly, the latter suggests that the herb may have hormonal effects. The main components of interest were kaurenoic acid, eudesmanolide lactones and luteolin. Experimentally, kaurenoic acid had a potent stimulatory effect on uterine contractions. Investigations have verified that extracts of Singapore Daisy also possess anti-inflammatory, analgesic and good broad-spectrum antibacterial activity (Balekar 2012; Mizokami 2012; Meena 2011).

ASTERACEAE: DAISIES OF THE APOTHECARY

Wedelia chinensis (formerly W. calendulacea) is an important herb of Asian origins. While it does not occur in Australia it deserves mention due to its considerable medicinal reputation. The remedy has tonic, anti-inflammatory, antitussive, antimicrobial and alterative properties. It has a rather extensive therapeutic repertoire, particularly for respiratory disorders including the treatment of bronchitis, pneumonia, whooping cough, haemoptysis (spitting blood), pharyngitis, tonsillitis, influenza, coughs, colds and headache.   The herbal decoction (seeds, flowers and/or leaves) has been valued as a deobstruent – a substance that removes obstructions in the body by opening up the natural passageways or pores. This was the basis of its febrifugal effect in fevers. Chinese Wedelia gained a particular reputation for the prevention of measles and diphtheria and their complications.  The herb is considered useful for various inflammatory conditions including articular inflammation (arthritis), cystitis (bladder infections) and laryngitis. It has also been recommended in Chinese and Malay traditions as an anti-hypertensive remedy. Furthermore, the leaf juice was frequently utilised as a snuff for headaches. In India the leaves provided a hair dye that was considered useful for promoting hair growth (Zakaria & Mohd 1994; Hong Kong CMRI 1984; Quisumbing 1951). Interestingly, Eclipta alba, a herb that has been used as a Wedelia substitute12, has a similar reputation for encouraging hair growth that has been supported by animal studies (Roy 2008). Substantial pharmacological evaluations of Wedelia chinensis support its clinical reputation. The antimicrobial and anti-inflammatory effects of the fresh leaf juice explain the herb’s efficacy in inflammatory skin conditions, including impetigo, abscesses, mastitis, boils and furunculosis (recurring boils). It has been utilised as an additive to baths for easing prickly heat rash (Van Dan 1993; Duc Minh 1993). Chinese Wedelia has a particularly good reputation as a liver-protective herb, and has therefore been recommended for hepatitis, hepatic and splenic enlargement – which has been supported by investigations showing strong hepatoprotective 12 Eclipta also has dye qualities and has been used as a tattooing agent, the juicy green leaves being rubbed over the scarifications to impart a deep bluish-black colour (Meena 2011).

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activity (see Table 2.1). The plant contains a variety of compounds that include saponins, tannins, isoflavonoids, carotenoids and wedelolactone which contribute to its complex pharmacology (Emmanuel 2001; Sharma 1989; Yang 1986). The plant decoction has also been taken as a haemostatic to ease menorrhagia (excessive menstrual bleeding) or uterine haemorrhage. Investigations of extracts have found a protective effect against osteoporosis – which may be linked to isoflavones and wedelolactone, components that possess phytoestrogenic properties (Annie 2006).

  A Weedy Medicinal: Eclipta alba

Eclipta alba (syn. E. prostrata). (Images courtesy Kim & Forest Starr, Hawaii)

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Eclipta herbal preparation. (Courtesy Acuneeds Pty Ltd, Sydney)

In some traditions Eclipta alba (syn. E. prostrata) has been utilised as a substitute for Wedelia calendulacea. Its use in India for liver and gall bladder disorders has been similar to that of Wedelia – and it has also provided a substitute for Dandelion (Taraxacum officinale). The remedy was highly recommended for jaundice and splenomegaly, and has shown potential benefits in hepatitis.   Studies of Eclipta alba have verified its hepatoprotective activity, as well as regenerative effects on the liver. The herb contains coumestans (wedelolactone, nor-wedelolactone, desmethylwedelolactone) that are similar to those found in Wedelia – with the hepatoprotective effects primarily linked to wedelolactone (an anti-inflammatory compound) and desmethylwedelolactone.  Clinically, Eclipta alba has been effectively combined with various other hepatoprotective herbs – Phyllanthus fraternus, P. niuri and Curcuma longa. Studies of a compound remedy called Tephroli (sourced from Tephrosia purpurea, Eclipta alba, Andrographis paniculata, Terminalia chebula and Ocimum sanctum) showed good results for the treatment of jaundice and viral hepatitis, with a concurrent significant improvement in

liver enzyme chemistry. Eclipta herb extracts have also demonstrated analgesic and antiviral properties – including activity against HIV – which support its use in Thai medicine for AIDS patients (Mithun 2011; Bhwana & Kumar 2010; Patel 2008; Tewtrakul 2007; Singh 2001, 1993; Zhang & Guo 2001; Mi 1997; Saxena 1993; Wong 1988; Chandra 1987; Jayaram 1987; Gopalakrishnan & Jayanthi 1986; Gupta 1986; Wagner 1986; Sankaran 1984; Satyavati 1976). Indian herbal traditions consider Eclipta alba to have general tonic properties useful as an antiageing remedy and in debility. It has digestive tonic (increase appetite, improve digestion) and bowel regulatory properties – as well as being useful for eye and ear infections. The herb has long been well regarded in treating diverse skin disorders, particularly as a wound-healing application for inflammation, cuts or burns,13 with the fresh leaf having a good reputation as a styptic agent (Mithun 2011). The leaf juice, combined with honey, was given to infants to treat catarrhal congestion and upper respiratory tract infections. Studies have shown antimicrobial (antibacterial, antifungal, anti-candidal) effects for various plant extracts – with light exposure having an interesting enhancement effect (Wiart 2004; Satyavati 1976). Extracts also had effective larvicidal activity against Aedes fluviatilis mosquitoes (Macedo 1997). The use of Eclipta as an antidiabetic remedy in Indian traditions prompted investigations into its hypoglycaemic attributes – which were found to be quite potent. Extracts also demonstrated good antioxidant and cholesterol-lowering properties. Moreover, it has shown analgesic and immunostimulant activity in animal studies, and has been incorporated into compound formulations for use in immune disorders with herbs such as Astragalus membranaceus and Ligustrum lucidum (fruit) (Mithun 2011; Jayathirtha & Mishra 2004; Sawant 2004; Liu 2000; Ananthi 2003; Bhattacharya 1997; He 1992). Other studies have indicated that the 13 The root can also be a useful local antiseptic for ulcers or wounds, especially for cattle. However, it has emetic and purgative properties if taken internally.

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herb also contains a number of components with anticancer potential: wedelolactone, luteolin, luteolin 7-O-glucoside and saponins (dasyscyphin-C and eclalbasaponin I) (Liu 2012; Mithun 2011). Indian traditions have utilised Eclipta alba as an antidote for snake bite. This is supported by a few intriguing investigations showing that extracts inactivated snake venom, exhibiting antimyotoxic (muscle toxin) and antihaemorrhagic effects. These activities were primarily attributed to wedelolactone, although stigmasterol and sitosterol were other anti-venom and antiinflammatory components in the plant extract. In Trinidad the leaf juice also has a reputation as an anti-venom agent against scorpion stings (da Fonseca 2010a; Pangal 2010; Diogo 2009; Perumal Samy 2008; Pithayanukul 2004; Syed 2003; Lans 2001; Melo & Ownby 1999; Melo 1994; Mors 1989).

Scorpion drawing (Heterometrus indicus) from JFW Herbst, Natursystem der Ungeflügelten Insekten, 1880. Eclipta alba has shown antidotal effects, including activity against snake venom and scorpion stings. While scorpions have a highly toxic reputation, only a few species (around 25) are known to contain a toxic venom that can result in fatalities.

 Chinese Wedelia as an Anticancer Remedy

Wedelia chinensis. (Courtesy Lorenzarius, Wikimedia Commons Project, CC-by-SA 3.0 Unported)

Herba Wedeliae (Wedelia chinensis) has been utilised as an anticancer treatment in Chinese medicine, primarily in formulations for cancer of the larynx and colon. The History of Medicinal Herbs in Fujian provides a comprehensive outline of its medicinal reputation: ‘The drug cures diphtheria, pharyngitis, tonsillitis, pneumonitis, pulmonary ulcer, whooping cough, nasorrhagia [epistaxis], haemoptysis caused by tuberculosis, haematuria, dysentery, measles, infectious hepatitis, rheumatic arthritis, insomnia caused by violent restlessness, gingivitis, carbuncle, and furuncle’ (Chang 1992). Many of these indications appear to draw on a measure of support for the immune system, as well as its significant antibacterial, anti-inflammatory and analgesic properties. Chinese Wedelia possesses a substantial vulnerary effect, ‘drawing out’ infection and actively healing wounds, particularly those due to ulceration or fistula. In cancer of the parotid gland the herb was pounded to a paste with the bulb of Allium bakeri and applied locally. The remedy has been well regarded as a detoxicant that will clear ‘heat’ (inflammatory symptoms). Inflammation is an important part of the process that supports tumour growth as well as its invasive and metastatic potential (Chang 1992).

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Wedelia chinensis extracts have good experimental anticancer activity. Recent investigations indicated excellent chemopreventive activity against sarcoma development in mice (Halder 2011; Meena 2011; Gupta 2007). Wedelolactone, luteolin, apigenin and indole-3-carboxylaldehyde are among the antitumour components that were identified with good effects against prostate cancer in animal studies (Tsai 2009; Lin 2007). Wedelolactone, in particular, can reduce the growth of various cancer cells and has been utilised in numerous experimental studies (Benes 2011; Vender 2008; Kobori 2004). Another potential anti-tumour compound, wedeloside, has been isolated from Wedelia asperrima (Oelrichs 1980). Kaurenoic acid is another antitumour component that is widespread in the genus (Peria 2010).

Classic Chamomile

The Chamomiles are attractive daisy-like herbs that can be quite difficult to tell apart. Both Matricaria chamomilla and M. recutita are among the naturalised remedies in Australia that were important components of the household medicine cabinet. (Image courtesy Erin Silversmith)

The name ‘Chamomile’ can be somewhat deceptive as it can refer to a number of herbs with a similar appearance. Their identification has been characterised by substantial confusion, in the use of both botanical and common names: • German Chamomile, Matricaria recutita (syns M. chamomilla, Chamomilla recutita) is also known as the Wild or Hungarian Chamomile. • Roman Chamomile, Chamaemelum nobile (syn. Anthemis nobilis) is also known as the English, Garden, Lawn, Scotch, Sweet or True Chamomile). The Corn Chamomile (Anthemis arvensis) is a •  different species.

Wild Chamomile growing beside a wheat field.

For decades, the identification of herbal products sourced from Roman Chamomile and German Chamomile was utterly confused. Their similarity of appearance resulted in numerous instances of misidentification – as well as incidents of substitution and adulteration that have been almost impossible to detect. Much of the older literature stated that Roman Chamomile oil had very similar activities to that of the German Chamomile, although later texts make a clear distinction between the two species.

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Calendula arvensis. (Courtesy Zachi Evenor, http://www. flickr.com/people/zachievenor)

Analyses of Matricaria recutita have shown it is distinguished by sesquiterpenes (azulene, bisabolol and derivatives), coumarins (umbelliferone, herniarin) and flavonoids (mainly apigenin, also quercetin, patuletin, luteolin and glycosides). Commercially, German Chamomile products are made from fluid extracts with a required minimum content of chamazulene and ɑ-bisabolol14 as the marker constituents. Tinctures prepared from Chamomile flowers (extracted with 30, 50 or 70% alcohol) require a ratio of 20 per cent flower weight per volume of alcohol. The alcohol content ensures that the constituents of the tincture are similar to that of alcohol-extracted essential oils (Mann & Staba 1986). Interestingly, a higher yield of essential oil can be obtained from the extraction of frozen flowers, rather than utilising the dried product (Carle 1989). German Chamomile (Matricaria recutita) and Roman Chamomile (Chamaemelum nobile) have similar, albeit not particularly potent, antibacterial properties. German Chamomile oil was shown 14 The Brazilian tree Vanillosmopsis erythropappa (Asteraceae) has been used as an adulterant of Chamomile oil. It contains up to 3% essential oil with a high concentration of ɑ-bisabolol (Carle 1990b) – a compound with significant antispasmodic activity (Achterrath-Tuckermann 1980). ɑ-bisabolol from Chamomile oil has also shown anti-leishmania activity with potential for use in the treatment of leishmaniasis (Morales-Yuste

The Corn Chamomile (Anthemis arvensis), from Prof. Dr. Otto Wilhelm Thomé, Flora von Deutschland, Österreich und der Schweiz, 1885, Gera, Germany. The Corn Chamomile (A. arvensis) and Stinking Chamomile (A. cotula) are naturalised in the temperate parts of the continent – primarily New South Wales, Victoria, South Australia and Tasmania. The Golden Marguerite or Yellow Chamomile (A. tinctoria, syn. Cotula tinctoria) is also naturalised in Tasmania and South Australia.

to be slightly more effective than that of Roman Chamomile – although the Moroccan ‘Chamomile’ (Ormenis multicaulis, syn. Cladanthus multicaulis) had a higher level of activity. German Chamomile oil does have active antifungal properties – although there are other oils, such as Thyme and Cinnamon, that are more effective at a lower concentration. Clove, Cinnamon and Thyme also possess more potent antimicrobial properties. Nevertheless, this does not preclude an appreciation of Chamomile’s antimicrobial effect when utilised as a woundhealing, anti-inflammatory agent (McKay & Blumberg 2006; Lis-Balchin 1998).

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Anthemis cotula, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. Anthemis cotula has sometimes been identified as a contaminant of German Chamomile, and contains anthecotulide, a problematic contact allergen (van Wyk & Wink 2004).

Matricaria recutita has long held official recognition as a valuable medicine due to its antispasmodic, sedative, anti-inflammatory, carminative and analgesic properties. The flowers were highly valued for gastrointestinal dysfunction (bloating, feelings of fullness, mild spasmodic disturbances and sluggish bowels), to reduce intestinal pain or colic, to ease menstrual and nervous system distress (nervousness, hysteria) and as a gentle tonic for general debility. The British Pharmaceutical Codex of 1934 provides an official evaluation of the herb’s diverse attributes: Preparations of chamomile are used internally to improve the appetite and aid digestion … ‘Chamomile tea’ (1 in 20 of boiling water; dose 1 to 4 fluid ounces) is a domestic remedy for indigestion and may be used as a vehicle for other bitters. The flowers are sometimes employed externally in the form of a poultice. Used as a fomentation, chamomile is a popular remedy in the early stages of inflammation; a decoction of chamomile

The English Lawn Chamomile or Roman Chamomile (Anthemis nobilis), from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. and bruised poppy capsules is also used as a fomentation for dental abscesses; the decoction is applied inside the mouth and the marc [macerated herb residue] is applied as a poultice. The extract may be combined in pills with purgatives to diminish the tendency to griping.

Its topical anti-inflammatory properties continue to be considered extremely useful for mouth and throat disorders, rhinitis (nasal inflammation), toothache, earache, eczema, wound healing, headache and influenza (PDR for Herbal Medicines 2004; van Wyk & Wink 2004). A combination of apple pectin and Chamomile extract is effective for childhood diarrhoea, even in infants. Chamomile is also recommended for infant colic (de la Motte 1997; Weizman 1993). Recent investigations suggest the herb has benefits for preventing the raised blood sugar levels characteristic of diabetes (Cemek 2008; Kato 2008). Research has substantiated many of these recommendations. Chamomile essential oil has antibacterial properties against gram-positive bacteria, skin fungi (dermatomyces) and Candida – which is largely attributed to the high ɑ-bisabolol content.15

ASTERACEAE: DAISIES OF THE APOTHECARY

Extract of Chamomile, from British Pharmacopoeia, 1867.

Dried Chamomile flowers. (Courtesy Henna Sooq LLC, www.hennasooq.com)

Flower extracts have similar antimicrobial properties, as well as substantial anti-inflammatory, antispasmodic, gastroprotective and anti-ulcer activity, which also appears linked to the bisabolol component.16 Various other components in the herb have a supportive role: azulenes (anti-inflammatory); esters and lactones (anti-mycobacterial); chamazulene, flavonoids, umbelliferone (antifungal against Trichophyton); quercetin, luteolin, apigenin (antimicrobial); ɑ-bisabolol and spiroethers (antispasmodic). Chamomile, apigenin and quercetin have also shown significant anti-allergenic potential (Al-Hashem 2010; Cemek 2010; Bezerra 2009; Altern Med Rev 2008; McKay & Blumberg 2006). The azulenes have important pharmacological properties. In addition to its significant antiinflammatory activity, chamazulene (which is formed from matricine during the steam-distillation process) has antioxidant, antipyretic, anodyne, antiseptic, antispasmodic and vulnerary properties (Mann & Staba 1986). Guaiazulene is a similar anti15 The anti-fungal activity of the essential oil against Aspergillus also supports its use as an antifungal agent in stored food products (Tolouee 2010). 16 Chamomile oil has also shown activity against Helicobacter pylori, which supports its anti-ulcer activity (Shikov 2008).

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inflammatory compound with hepatoprotective and liver cell regenerative attributes (Kourounakis 1997a, 1997b). Certainly Chamomile possesses good antiallergic properties that make it useful for itching skin disorders (Chandrashekhar 2011; Lee 2010; Kobayashi 2005, 2003). Chamomile is one of the richest known natural sources of apigenin (840 mg/100 g), which would certainly exert an influence on the properties of the herbal remedy (McKay & Blumberg 2006). Apigenin possesses antispasmodic17, mild anxiolytic and sedative activity – as well as anticancer potential (chemopreventive and antimutagenic activity) (Anter 2011; Srivastava & Gupta 2009, 2007; Avallone 2000). Chamomile has a good clinical reputation as an anti-anxiety and insomnia remedy (Awad 2007; Zick 2011; Amsterdam 2009; Gould 1973). There is a particularly interesting study with regard to the use of Chamomile oil by over 8,000 women (applied to the skin or used as an inhalant) that found it was effective for reducing pain during labour and delivery (Burns 2000). During menopause, in combination with Angelica sinensis, it can help to to alleviate sleeplessness and regulate hot flushes18 (Kupfersztain 2003). In addition, the mild sedative properties may be useful for hyperactivity (ADHD), suggesting its use as part of a broader management strategy (Niederhofer 2009). Surprisingly, Chamomile extracts have antiviral properties against poliovirus and herpes virus – with clinical potential for use in Herpes genitalis (Koch 2008a, 2008b). The wound-healing attributes of Chamomile are effective for burn injuries and dermabrasion (tattoo removal) – and were even shown to be superior to corticosteroids for treating ulceration (Jarrahi 2010, 2008; Martins 2009; Nayak 2007; Glowania 1987). The herb’s potent anti-inflammatory, immune-supportive and healing attributes suggests its use to modify the side-effects of chemotherapy and radiation treatments, including the prevention of infections, mucositis (inflammation and ulceration of the gastrointestinal tract), stomatitis (mouth inflammation) and phlebitis (inflammation 17 10 mg of apigenin has shown antispasmodic activity equivalent to 1 mg of the opioid antispasmodic papaverine (Achterrath-Tuckermann 1980). 18 There may also be a direct hormonal influence of the herb. Experimental studies have suggested potential benefits for osteoporosis (Kassi 2004) – although this requires further clarification.

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of a vein) (Ghonime 2011; Pavesi 2011; Reis 2011; Mazokopakis 2005; Carl & Emrich 1991). Bisabololoxide A is a component that may provide a potentiating agent in combination with the anticancer drug 5-fluorouracil – which may reduce the drug dose and the risk of side-effects (Ogata-Ikeda 2011). Some studies have also suggested Chamomile may have neuroprotective potential against cerebral ischaemia, and anti-seizure effects (Ranpariya 2011; Chandrashekhar 2010; Heidari 2009) – as well as very interesting inhibitory effects on morphine dependence and withdrawal symptoms in animal studies (Gomaa 2003). However, it is possible that Chamomile may interact with warfarin and individuals on this drug should be cautious in its use (Segal & Pilote 2006) – although this may also be linked to an individual sensitivity reaction.

A Complex Essential Oil

Overall, around 120 constituents have been identified from German Chamomile flowers.19 The essential oil (yield 0.4–2%) is characterised by ɑ-bisabolol and chamazulene (50–65%). Other oil components include: ɑ-bisabolol oxides, cadinene, farnesene, furfural, spathulenol, proazulenes (matricarin and matricine), spiroethers and sesquiterpenes (anthecotulide) (Altern Med Rev 2008; McKay & Blumberg 2006). The following analysis is an indication of the proportions involved: ɑ-bisabolol (57%), trans,trans-farnesol (16%), cis-β-farnesene (7%), guaiazulene (4%), ɑ-cubebene (3%), ɑ-bisabolol oxide A (2%) and chamazulene (2%) (Tolouee 2010). Aromatic compounds with useful fragrance qualities of interest for perfumery purposes include farnesol20, an aromaenhancing agent that, in low Chamomile oil. (Courtesy amounts, acts to enhance Mountain Rose Herbs)

floral scents. Other fragrant components include borneol, a common additive in perfumed soaps and detergents. Bornyl acetate has similar characteristics, while ɑ-bisabolol is a perfume fixative. Nerolidol, which is present in Roman Chamomile, possesses a sweet Apple or Rose-like aroma that is a useful harmonising agent in scents (Mann & Staba 1986).

Dandelion: A Famed Liver Tonic

The ubiquitous Dandelion (Taraxacum officinale) is found throughout the southern temperate regions of Australia (New South Wales, Victoria, Tasmania and southwest Western Australia) – and there is even a record of its presence as far inland as Alice Springs. The different species can be difficult to tell apart and the name Taraxacum officinale has probably been applied, at some time or other, to the majority of Dandelions found in Australia.21 There are a couple of native species: Tataxacum aristum and T. cygnorum from Tasmania and Victoria – with the latter ranging to South Australia (but considered extinct in Western Australia). The Mountain Dandelion (Taraxacum aristum) is also found around the New South Wales–Victoria border. Naturalised species include the Russian Dandelion, Taraxacum kok-saghyz (Tasmania); T. squamulosum (Victoria); T. hepaticolor and T. khatoonae (South Australia). The common small golden-flowered Dandelion was an early herbal import. The perception of this plant as a commonplace weed, however, has possibly marred a wider appreciation of the remarkable potential of the remedy. Little is known about the medicinal properties of the native Australian species (Taraxacum aristum and T. cygnorum) – although the use of other members of the genus in Asian, Indian and European traditions shows enormous scope. European herbal wisdom has long recommended 19 Among those of importance are flavone glycosides (apigenin 7-glycoside and derivatives) and flavonoids (luteolin glucosides, quercetin glycosides, isorhamnetin) (around 8%), as well as other phenolics (cinnamic acid derivatives, mainly ferulic and caffeic acids). In addition, mucilage polysaccharides (10%) are present and small amounts of choline (0.3%) and coumarins (0.1%). 20 Isoprenoids such as farnesol and geraniol have also attracted interest for their anticancer potential. 21 There has been plenty of room for confusion. Estimates of the number of species in the genus range from 30 to 57 (with many microspecies), divided into nine sections. European herbal traditions use T. officinale, with the main suppliers being Yugoslavia, Romania, Hungary and Poland. Taraxacum platycarpum is used in Chinese medicine (Schulz 2006) – as is T. mongolicum (Yeung 1985).

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leaves in white wine, or the leaves chopped as pot herbs with a few alisanders22, and boiled in their broth, are very effectual. And whoever is drawing towards a consumption [tuberculosis, wasting], or an evil disposition of the whole body called cachexy [poor health, debility], by the use hereof for some time together shall find a wonderful help. It helpeth also to procure rest and sleep to bodies distempered by the heat of ague fits, or otherwise; the distilled water is effectual to drink in pestilential fevers, and to wash the sores.

While this may appear to be overstating the case for Dandelion as a paragon of multiple virtues, recent research into its antibacterial, antiviral, immunomodulatory, anti-inflammatory and potential anticancer activity have to agree that this is a rather remarkable herbal remedy.

Dandelion, from Franz Eugen Köhler, Köhler’s MedizinalPflanzen, 1897.

Dandelion as a diuretic and cleansing liver tonic with detoxicant properties considered useful for blood purification, which led to its use for clearing skin blemishes. The herb also had a circulatory supportive effect, antacid properties, and an ability to restore gastric function following episodes of severe emesis. The latter could possibly be linked to the fact that Dandelion is rich in minerals (particularly potassium, calcium, sodium) and is an excellent source of vitamins B, C and E (Altern Med Rev 1999). Studies also suggest a cholinergic stimulatory effect with benefits for digestive function (Jin 2011). Nicholas Culpeper (1653) wrote that Dandelion had: an opening and cleansing quality, and therefore is very effectual for the obstructions of the liver, gall, and spleen, and the diseases that arise from them, as the jaundice and hypochondriac; it openeth the passages of the urine both in young and old; powerfully cleanseth imposthumes [abscess] and inward ulcers in the urinary passages, and by its drying and temperate quality doth afterwards heal them; for which purpose the decoction of the roots or

Taraxacum succus. (Courtesy The Apothecary, Cairns)

Taraxacum, from the Extra Pharmacopoeia Martindale, 1941. 22 Smyrnium olusatrum, a plant of the Umbelliferae, with a celery/parsley type of flavour.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary taken one of two tablespoonfuls two or three times daily – Cooley’s Practical Receipts.

The roots were considered to be in best condition for harvest in early winter. He concluded: ‘A good demand for properly-dried roots, free from earth and any foreign substances, always exists, and considering the little trouble of cultivation and harvesting, the price obtained may almost be looked up on as clear profit.’

Taraxacum, from the British Pharmaceutical Codex, 1934,

In 1893, T Phillips-Gibson noted that Dandelion ‘has been introduced and succeeds well in many parts of Australia’, although he does caution about its propensity to become a troublesome weed once established. With regard to its practical use he comments: There are several preparations of dandelion weed used in medicine, the British Pharmacopoeia recognising a decoction, extracts from both the fresh and dried roots, as well as an extract of the juice in spirit. The decoction is made by boiling 1 oz. of the root in a covered vessel, and, after being strained, the liquid made up to a pint by adding more water; the dose being two to four teaspoonfuls. The extract is more difficult to prepare. It is made as follows:- The fresh root is bruised, and the juice allowed to settle; the liquid is then heated to 212deg:F, this heat maintained for ten minutes, and the extract afterwards evaporated till it is thick enough to be made into pills. A good preparation for domestic use is made with 4 oz. of the fresh roots in 1½ pints of water, and boiling down to 1 pint, and then straining. This can be

Dandelion root, from Alice Henkel, ‘Weeds Used in Medicine’, US Department of Agriculture, Farmer’s Bulletin, 1917. The use of dandelion extracts as a flavouring for various food products (alcohol, soft drinks, desserts, confectionary, baked goods, puddings, cheese), or roasted as a coffee substitute, appears to have diverse unappreciated benefits in light of recent research on the medicinal properties of the herb.

Clinically, Dandelion has significant diuretic effects with the potential to replenish potassium and magnesium levels (leaf content: 42.5 mg/kg and 2.5 mg/kg, respectively). This is important as hypokalaemia (low potassium) and hypomagnesia (low magnesium) are serious side-effects of conventional diuretics. Some studies have shown that extracts obtained from the herb were consistently stronger in activity than root extracts (Clare 2009; Altern Med Rev 1999; Racz-Kotilla 1974). Dandelion contains a number of other components (primarily

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The most abundant phenolic compounds in Dandelion flowers and leaves are hydroxycinnamic acid derivatives – notably chlorogenic, dicaffeoyltartaric (chicoric) and monocaffeoyltartaric acids (Schutz 2006). Extracts of Dandelion flowers have significant antioxidant properties which are linked to these phenolic components. Coumarins (aesculin, cichoriin) and numerous flavonoids are also present (Hu & Kitts 2005; Williams 1996).

flavonoids) of pharmacological interest23 with diuretic attributes: caffeic acid (anti-aggregant, antiinflammatory, antioxidant, anxiolytic), chlorogenic acid (anti-inflammatory, antioxidant, cardioprotective), isoquercitrin (anti-inflammatory, antioxidant, hypotensive) and luteolin24 (anti-inflammatory, antioxidant, hypocholesterolemic, vasodilator), as well as mannitol (anti-inflammatory, antioxidant) (Duke 2011). 23 For a comprehensive appraisal of the chemical components of the genus see the review by Katrin Schutz (2006). 24 The anti-inflammatory properties of luteolin appear to be supported and enhanced by chicoric acid in the herb (Park 2011b).

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Chicory (under the old name Succory), Cichorium intybus, was known to herbalists of old as a plant for healing the liver and the lungs. Nicholas Culpeper (1653) asserted that ‘A handful of the leaves or roots, boild in wine or water, and a draught drunk fasting, driveth forth choleric and phlegmatic humours, openeth obstructions of the liver, gall and spleen; cureth the yellow jaundice, the heat of the reins [kidneys], and of the urine.’ The wine-based decoction was excellent for fevers – while the seed powder could help prevent a ‘fit of the ague’. The leaf poultice (or a wash with vinegar) could remedy all forms of skin problems (pustules, wheals, pimples, pestiferous sores, inflammation), conjunctivitis, allay ‘swellings’ and St Anthony’s fire. The ground root has retained its fame as a liver detoxicant. It has long been used by the French as a coffee adulterant, to counteract the stimulating effect of caffeine (Leyel 1937) – although more recent practices utilise the root as a coffee alternative.

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as an anti-diabetic remedy with extracts showing anti-hyperglycaemic activity, as well as effects on metabolism that suggest benefits for diabetes, atherosclerosis and obesity (Goksu 201; RodriguezFragoso 2008; Onal 2005; Petlevski 2003, 2001; Altern Med Rev 1999): • Root extracts have blood sugar-regulating properties that may be linked to a high content of inulin, a polysaccharide fibre that helps prevent blood sugar fluctuations (Altern Med Rev 1999). • Oligofructans from the herb may have a potential role for maintaining colonic bifidobacteria levels (Trojanova 2004). Root and leaf extracts have cholesterol•  lowering (hypolipidaemic) properties with antiatherosclerosis potential (Choi 2010). • Extracts have pancreatic lipase (the key enzyme for dietary fat digestion) activity, which suggests that the herb may be of use as an anti-obesity agent (Zhang 2008). •  In addition, preliminary investigations of Dandelion’s anti-inflammatory effects suggest a protective role in pancreatitis (Seo 2005). Dandelion weed, showing the toothed leaves. The genus name originates from the French dent-de-lion, from a fancied resemblance to the ‘tooth of the lion’.

The traditional use of Dandelion as a hepatoprotective and cholagogue (increasing the flow of bile) is supported by a number of studies. It can protect against alcohol and various forms of chemical injury to the liver, as well as enhancing its regenerative properties (Park 2011a, 2010a, 2010b; Domitrovic 2010; Mahesh 2010; You 2010). It should come as no surprise that the herb has significant antiinflammatory and antioxidant properties, which would be valuable in a number of different conditions including the prevention of lung tissue injury (Liu 2010). Studies also suggest a protective effect on the central nervous system (Kim 2000). Flower and root extracts (Taraxacum officinale, T. platycarpum) have been reported to possess excellent anti-oedema properties. Root extracts attracted additional interest when their activity was shown to be significantly improved in combination with the anti-inflammatory drug indomethacin (Hagymasi 2000a, 2000b; Yasukawa 1998, 1996; Tita 1993; Mascolo 1987). Dandelion has had an interesting reputation

A Traditional Anticancer Herb   Chinese Dandelion

Chinese Dandelion (dried flower for medicinal use, pictured) is sourced from Taraxacum mongolicum, T. officinale and T. sinicum.

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The fact that other Taraxacum species have equally interesting medicinal potential is evident by the use of the Chinese Dandelion (T. mongolicum) as a cleansing, anti-inflammatory, antibacterial and healing agent. Recommendation as a toxinneutralising remedy has seen it employed in ‘heat’ conditions – abscesses, sores and nodules. It is particularly useful for dissipating ‘hard nodules’, as well as for treating breast or intestinal abscesses. Additionally, the Chinese Dandelion can be used as a lactogen to promote lactation25 (Bensky & Gamble 1986; Yeung 1985). The herb has been highly regarded for soothing ophthalmic problems characterised by redness, swelling and pain of the eyes (conjunctivitis). Extracts have shown activity against a wide range of bacteria – including the causative agents of gastrointestinal and respiratory disorders: Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Shigella spp., Neisseria meningitidis, Corynebacterium diphtheriae, Mycobacterium tuberculosis (Bensky & Gamble 1986, Yeung 1985). Taraxacum formosanum has similar antibacterial effects against Streptococcus aureus and Mycobacterium tuberculosis, as well as Leptospira (Leu 2005). The use of Chinese Dandelion as an antibacterial agent is well established in traditional herbal practice. However, the high mineral content of this herb has the potential to

Acne formula from Cathay Herbal which has Chinese Dandelion as a major ingredient. (Courtesy Cathay Herbal) 25 While Dandelion is not normally thought of as having hormonal properties, there are a couple of studies that have suggested effects on oestrogen receptors and an anti-fertility effect in male rats (Tahtamouni 2011; Zhi 2007).

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The white-flowering Japanese Dandelion (Taraxacum albidum) is a cross between T. coreanum and T. japonicum. (Courtesy Mokimisato, Wikimedia Commons Project, CC-by-SA 3.0 Unported)

limit the absorption of quinoline antibiotics (e.g. ciprofloxacin). Therefore, it would be advisable to ensure that the herb and this type of drug are not taken at the same time (Zhu 1999). Interestingly, Chinese Dandelion has a good practical anticancer reputation and is traditionally included in compound prescriptions for treating leukaemia, gastric cancer, and cancer of the breast or cervix (Menghini 2010; Sigstedt 2008; Koo 2004; Takasaki 1999a, 1999b; Chang 1992): • In breast cancer treatments Chinese Dandelion was used in combination with Snakegourd fruit (Trichosanthes kirilowii), Olibanum (Frankincense, Boswellia carterii), Myrrh (Commiphora myrrha), Gan Cao root (Chinese Liquorice, Glycyrrhiza uralensis) and Tangerine or Mandarin Orange leaves (Citrus reticulata) – the herbs being mixed with wine before being taken. •  Chinese Dandelion has also been used for treating cancers of the nasopharyngeal region and mouth (gingival or hard palate). In the Renewed Compilation of Mei’s Experienced Recipes some specific details are provided: ‘Herba Taraxaci, with only one stock about 0.3 meter high, two flowers and a root as large as a human fist, cures dysphagia [difficulty swallowing] with

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a miraculous effect if pounded and taken with wine’ (Chang 1992). •  The strong antioxidant and anti-inflammatory properties of Dandelion (T. officinale and T. japonicum) may play a role in its immune supportive and anti-tumour activity (Koh 2010; Jeoan 2008; Kim 1999, 1998). • In addition, herb extracts have demonstrated activity against liver cancer cells, while root extracts showed anti-leukaemic properties – which may be linked to a number of components with anticancer potential – taraxinic acid26, taraxasterol and taraxerol (Ovadje 2011; Koo 2004; Choi 2002).

Of these, the Chinese Dandelion root exhibited antimelanoma properties associated with its lupeol content (Hata 2000). Luteolin and luteolin 7-glucoside from Taraxacum officinale flowers contributed to its significant antioxidant and cytotoxic properties (Hu & Kitts 2005, 2003). Investigations have also found that Taraxacum mongolicum had anti-inflammatory and immune-modulating actions, and antiviral activity against the Herpes simplex virus (Kim 2011; Luo 1993; Zheng 1990).

Chinese Dandelion herb.

The anticancer potential of diverse natural products as anti-melanoma agents has been a recent topic of considerable interest. A Japanese investigation evaluating a wide variety of natural products (25 types of seaweed, 26 mushrooms, and extracts of 49 wild plants) found that extracts of all the herbs belonging to the Compositae (now Asteraceae) family, subfamily Cichorioideae, had an effect on melanoma cell lines. 26 This compound is prevalent in the genus. For the purposes of this study it was isolated from a Korean species, T. coreanum, which is utilised similarly to the common Dandelion as an anti-inflammatory and diuretic remedy (Choi 2002)

Taraxacum platycarpum has been traditionally utilised as an anti-inflammatory for gastrointestinal disorders (ulcers and colitis). It contains a polysaccharide with immune potentiation and anti-tumour activity, as well as an anti-allergic component27 (desacetylmatricarin) and an anticoagulant agent (Yun 2002; Cheong 1998; Jeong 1991). Similar immunomodulatory and anti-tumour activities have been reported for Taraxacum officinale (Altern Med Rev 1999). (Upper image courtesy Tsutomu Otsuka, flickr; lower image courtesy Hatimaki, flickr) 27 It should be noted that there are reports of contact dermatitis associated with Dandelion – however, these reports only appear to be linked to contact with the plant pollen, and not the herb itself.

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Dandelions for Rubber and Gas The fact that synthetic rubber is a petroleumbased product that is becoming progressively more expensive has sent researchers looking for alternative natural rubber-yielding plants. The cultivation of the classic rubber resource, Hevea brasiliensis, is limited by a form of leaf-blight (due to Microcyclus ulei) and the fact that the crop takes a long time to reach maturity. The establishment of plantations can also have a significant negative environmental impact. Alternatives are Guayule (Parthenium argentatum), which is a fairly slowgrowing desert plant, and the Russian Dandelion (Taraxacum kok-saghyz), the sap of which can produce good quality rubber (Buranov & Elmuradov 2009; The Economist 2009; Wahler 2009; van Beilen & Poirier 2007). Interestingly, the use of Russian Dandelion as a rubber resource was suggested during World War II. A review of its potential was produced by WG Whaley and JS Bowen in 1947 for the US Department of Agriculture – although the processing costs were considered prohibitive at the time. This species, like the Common Dandelion, is also an inulin resource that can be turned into bioethanol using fermentation processes – thereby leading to the suggestion of its use as a biogas fuel resource (Van Beilen & Poirier 2007).

The Russian dandelion (Taraxacum kok-saghyz) was discovered in Kazakhstan in 1932 by USSR scientists searching for a domestic rubber resource. It was subsequently cultivated as a crop and used for tyre manufacture by Russia and Germany during World War II. The plant was introduced into Tasmania by visiting American forces at this time. (Image courtesy Ford Motor Co., USDA publication)

Marigolds: Treasure in the Garden

Calendula officinalis. (Images courtesy Herbert Zell)

Achenes (seed-containing fruit) of Taraxacum koksaghyz. (Tracey Slotter, USDA; provided by ARS Systematic Botany and Mycology Laboratory, Yugoslavia)

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‘Marigold’ commonly refers to species of Tagetes and Calendula – both of which have excellent reputations as wound-healing and febrifugal agents. Calendula, which is a familiar garden escapee across the world, has its origins in the Mediterranean and the Atlantic islands, while Tagetes is native to South America and Mexico. The edible leaves and flowers of both herbs can be used as salad ingredients and are popular herbal teas. Powdered Marigold flowers also provide a colouring and seasoning in a similar manner to Saffron. The active dye flavonoids from Calendula officinalis (patulitrin, patuletin) are only found in the blossoms during and after flowering, and cultivation conditions similar to the Mediterranean climate type are important for their production (Guinot 2008). For centuries Calendula has maintained an impressive therapeutic reputation in Europe. Its

The seed-containing achenes of Calendula make an interesting display when the plant is in fruit. The bloom is composed of individual florets that result in this seed head configuration. (Images courtesy Herbert Zell)

efficacy, similar to that of many wound-healing herbal medicines, has been based on the fresh plant. The simplest way of using it is to apply the golden flowers or pulped plant as a dressing, although a tincture, with good keeping qualities, was easily prepared. Dr Dorothy Shepherd, who wrote of her extensive clinical experience with herbal and homoeopathic medicines in A Physician’s Posy, recommended a tincture based on the use of half-opened buds or newly-opened flowers (with gummy end-shoots), pounded and macerated in 50 per cent alcohol. The mixture was regularly shaken (several times daily) for three weeks. It was then filtered and stored for use. A fresh juice or succus could be made by pulping the whole plant (including pre-soaked roots), which provided a lotion for immediate use, or alcohol could be added as a preservative (Shepherd 1969). Dr Shepherd’s praise of Calendula was effusive: ‘The Marigold is a wonderful flower, a magic herb; looking at it, it raises one’s spirits, gives one hope … its uses are manifold. It provides the healing touch of nature and prevents the spread of disease, the spread of sepsis – a wonderful mission.’ She considered it an essential part of the household medicine cabinet: ‘It is the best herbal wound dressing and antiseptic that I know. Alack and alas! that so few, even keen homoeopaths, appreciate its value as such. I worked for years in various homoeopathic hospitals and never saw it used; we used the same lotions, tinctures and dressings as the orthodox hospitals. And yet there were a few valiant spirits who prescribed Calendula in wound treatment. Such a one was Dr. Carleton, who used it in peace time in his hospital in America as a dressing in all kinds of surgical work and for different types of operations.’ She mentions his use of the tincture (dilution 1:25) for amputation procedures, trephining the skull, gum swelling following dental work, haemorrhage after circumcision, and ‘mopping out the inside of the abdominal cavity after operations for abdominal tumours and ovarian cysts’. Calendula is a specific for clean cuts, incised wounds, and painful breaks in the skin surface such as gum ulcerations, cracks inside the nostrils or on the heel of the foot. It has been highly regarded as a healing agent in maternity cases, applied to wounds and incisions of the vulva and perineum. Healing was said to progress so well that it took ‘place in less than half the usual time’.

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Calendula tincture is useful for numerous types of skin problems and infections (bruising, ulceration, boils) as well as wounds (to stop bleeding and promote healing). (Image courtesy Dr. Reckeweg & Co., Bensheim, Germany)

Calendula officinalis. (Courtesy Teun Spaans, Wikimedia Commons)

While the herb was preferentially employed to prevent infection, Dr Shepherd also mentioned its use for infected wounds, including ulceration or septic gums: ‘Calendula officinalis is not an antiseptic in the true meaning of the word; but it is a fact that germs do not thrive in its presence, it inhibits their growth and even if wounds are already badly infected I have seen offensive, purulent discharge become clear and sweet-smelling in a day or two. Calendula is wonderfully soothing as an external application, it neither destroys nor irritates any new epithelial cells which are forming; it rather stimulates their growth.’ Additionally, Calendula was a highly effective styptic useful for bleeding cuts, wounds, grazes, and even haemorrhagic injuries. Dr Shepherd lamented the lack of commitment regarding the recognition of herbal medicines such as Calendula: ‘I wish more lay people would have greater conviction in their faith, and boldly admit what has cured them, and invite their doctors to experiment at first with such simple remedies as Calendula and Arnica, and later go into it more thoroughly and scientifically. We should get somewhere!’ Close to half a century later there appears to be some good news in this respect. Certainly she would have been impressed with recent innovations suggesting the use of Calendula-impregnated nanofibres as wound dressings (Vargas 2010).

 Calendula: Favoured Herb of the Ancients Edward Hamilton (1852) provides the following review of Calendula, quoting

Calendula drawing from Edward Hamilton, Flora Homoeopathica: Illustrations and descriptions of the Medicinal Plants used as Homoeopathic Remedies, Leath & Ross, St Paul’s Churchyard, Oxford St, London, 1852.

numerous authorities. Of particular interest is its reputation for painful conditions and in the treatment of cancerous growths: The ancients considered the Calendula a deobstruent remedy, exerting a great influence on the circulation. Dioscorides recommends it in cancer; and Fuchsius (Hist. Stirp., 1546) prescribed the juice of it against toothache … Gerarde, also, in describing its virtues

[[cap [[cap [[cap

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary remarks, ‘that the flowers and leaves of Marigold being distilled, and the water dropped into red and watery eyes, ceaseth the inflammation and taketh away the pains.’ Calendula was formerly in much request as a medicine, and was used more especially in carcinoma and scirrhus [a hard cancerous growth]; according to Westring, with great effect in the third stage, particularly in diminishing the pain, and rendering the pus less corroding; but on further experiment by others, the same effects were not produced28, and therefore it was thrown aside. It was also used in chlorosis [anaemia], hysteria, epilepsy, jaundice, and some kinds of dropsy. Schneider found it of great efficacy as a lotion to fresh wounds, inducing union by the first intention. Zorn considered Calendula of great service in throwing out the eruption of measles and small-pox; and as a topical application to stop the bleeding in haemorrhoides fluentes. It was a favourite remedy with Boerhaave, who employed it in uterine diseases, in diseases of the kidney, and jaundice. Its chief use, however, was for cancer, and it was the principal ingredient in the famous Rust Pill, which consisted of oxide of iron, colewort, and extract of Marigold. W. Carter found the extract of Calendula of great assistance in obstinate vomiting; and De Camp, in a case of cardialgia [cardiac pain], where all medicines, etc., were vomited up, owing to a great irritability of the stomach. Muhrbeck used the extract of Marigold, in chronic vomiting, with great success, in a case where violent pains were felt at the same time in the region of the uterus; it was remarked that these pains increased when the dose exceeded thirty-four grains in the twenty-four hours. It is interesting to note that Elgafaki states that violent vomiting ensues after taking four drachms of the juice of Marigold. Dr. Stein extols the efficacy of this plant in cancer of the skin; he prepares the juice from the green plant and its blossoms, and makes an ointment with butter and charcoal, which is applied to the ulcer. 28 Dr Shepherd emphasised that the quality of the preparation was of paramount importance and could well account for variation in the efficacy of the remedy.

The skin rejuvenation, anti-inflammatory and hydrating properties of Calendula creams have made the herb popular for cosmetic purposes (Akhtar 2011). Recent studies evaluating effective preparations for clinical use found a Calendula cream using a

hydrophilic base and a complex emulsifier was the best choice for preventing microbial contamination. This combination maintained the integrity of the carotenoids, polyphenols and flavonoids that were identified as the primary antioxidant components. Calendula oil prepared with saturated oils is also very stable with regard to carotenoid content (Bernatoniene 2011; Bezbradica 2005). Calendula leaf and flower poultices or decoctions have been well regarded as anti-cancer remedies employed for treating skin growths (warts, cancer), breast and uterine growths, ‘glandular indurations’ and cancerous ulcers. Investigations showing antiinflammatory, antioxidant, immune-stimulant, antimetastatic, cytotoxic and anti-tumour promotion properties certainly lend significant support to these recommendations. Calendula’s protective effects on skin tissue may be equally useful against the development of skin cancer (Preethi 2010, 2009, 2008, 2006; Fonseca 2011, 2010a, 2010b; Herold 2003; Jimenez-Medina 2006; Ukiya 2006; Varlijen 1989; Boucard-Maitre 1988). In addition, initial studies have suggested that Calendula extracts can protect against cellular injury associated with cigarette smoke exposure (Ozkol 2011). Safety assessments agree on the non-toxic properties of Calendula and it is now widely available in creams, oils and lotions for easing inflammatory skin disorders. However, there is a specific caution for individuals who are sensitive to plants of the Asteraceae family as they can suffer allergic dermatitis from exposure to the herb. It is always wise to be aware of such sensitivities (Andres 2009; Reider 2001). Although a number of components such as coumarins (e.g. herniarin; Paulsen 2010) have been implicated in allergic reactions, bisabolol is one of the more common allergens (Russell & Jacob 2010). A number of studies have confirmed the antimicrobial properties of Calendula extracts29 against both gram-positive and gram-negative bacteria. Water-based extracts with effective antibacterial properties had particularly good activity against Staphylococcus aureus, as well as Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. Leaf extracts have similar antibacterial properties, showing the 29 Oleanolic acid from Calendula flowers has also shown antibacterial activity against gram-positive bacteria, while oleanolic acid glycoside had antiparasitic properties against the larva of an intestinal parasitic nematode (Heligmosomoides polygyrus) (Szakiel 2008).

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greatest activity against Klebsiella pneumoniae (Bissa & Bohra 2011; Roopashree 2008; Dumenil 1980). Other studies have shown activity against the gastric pathogen Campylobacter jejuni, which supports its use as an antidiarrhoeal agent, particularly in childhood diarrhoeal disorders (Cwikla 2010). The antispasmodic properties of flower extracts may also help in gastrointestinal disorders (Bashir 2006). The reputation of Calendula oil as a healing agent for mouth problems (sore gums, ulceration, cheilitis, dental problems) is equally well supported by studies showing activity against a range of periodontal bacteria. However, the type of solvent utilised and the method of preparation are highly influential with regard to the efficacy of the remedy (Machado 2010; Roveroni-Favaretto 2009; Iauk 2003; Modesto 2000). The antifungal activity of Calendula essential oil extends to diverse Candida species (C. albicans, C. dubliniensis, C. guilliermondii, C. parapsilosis, C. glabrata, C. krusei, C. tropicalis) and to Rhodotorula spp., indicating good potential for use in yeast infections including vaginal candidiasis30 (Gazim 2008a). Calendula oil’s antibacterial and analgesic properties suggest that it could be useful for ear infections (otitis media31) (Saify 2000; Shaparenko 1979). Calendula’s excellent anti-inflammatory, woundrepair and burn-healing attributes have been verified by numerous studies – with potential for use in serious conditions such as venous leg ulcers, or to prevent tissue damage due to radiation therapy following breast cancer surgery (Parente 2011; Preethi & Kuttan 2009a, 2008; Chandran & Kuttan 2008; Leach 2008; Pommier 2004; Duran 2005; Amirghofran 2000; Dietz 1998; Lievre1992; Rao 1991; Klouchek-Popova 1982). There are also indications of hepatoprotective and renoprotective potential, as well as anticancer activity against liver cancer (Manal 2010; Preethi & Kuttan 2009b; Ali & Khan 2006; Gupta & Misra 2006; Rusu 2005; Cordova 2002; Lin 2002). The anti-inflammatory and healing attributes of Calendula are also of interest for gastrointestinal disorders such as colitis and ulceration. Some of the active components were identified as calendasaponins32 30 Calendula has been recommended in a douche preparation (with Thuja, Gotu Kola, Yarrow, propolis, German Chamomile, and Roman Chamomile) for the treatment of cervical dysplasia. See Katolen Yardley (2001) for full details of the treatment protocol. 31 A clinically effective formulation for the relief of ear pain contained a combination of Garlic, Verbascum thapsus, Calendula officinalis flowers, Hypericum perfoliatum, Lavender and vitamin E in olive oil (Sarrell 2001).

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Field Marigold (Calendula arvensis). The Field Marigold is widespread in southeastern Australia, ranging to Tasmania and South Australia. Calendula flower extracts possess antiviral activity against HIV, Herpes simplex and influenza viruses with interesting clinical potential (Kalvatchev 1997; Bogdanova 1970). Triterpene saponins from Calendula arvensis have demonstrated antiviral activity (De Thommasi 1991, 1990). (Image courtesy Zachi Evernor, flickr)

with gastroprotective and hypoglycaemic properties (Yoshikawa 2001; Borrelli 2000; Chakurski 1981, 1980) – while Calendula polysaccharides had a protective mucilaginous effect on irritated mucous membranes. Some polysaccharides (heteroglycans) also have immune-stimulating properties (Schmidgall 2000). Another study has suggested that Calendula could have cardioprotective properties against the ischaemic injury that accompanies a heart attack (Ray 2010). 32 Saponins have been isolated with anti-inflammatory, haemolytic and molluscicidal activity (Mostafa & Tantawy 2000; Helaly 1999; Chemli 1990). Triterpene glycosides such as faradiol have shown significant antioedemic activity comparable to indomethacin. Faradiol esters and psitaraxasterol possess similar activity, albeit less potent. Another study isolated a faradiol ester in Calendula flowers with significant anti-inflammatory activity. The triterpene calenduloside B (isolated from Calendula roots) also has effective anti-ulcer properties (Marukami 2001; Zitterl-Eglseer 2001, 1997; Della-Loggia 1991, 1990; Chakurski 1981a, 1981b; Shipochliev 1981; Iatsyno 1978).

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The golden-flowered Calendula is considered to have a wide variety of therapeutic properties: wound healing, analgesic, antispasmodic, astringent, antimicrobial, emmenagogue, carminative, laxative and anthelmintic. The herb has been popularly utilised as a febrifuge in conditions as diverse as cholera, typhus, colds, and influenza. Investigations have identified various compounds with a range pharmacological Calendula: a quality tincture. of (Courtesy The Apothecary, properties that include anti-inflammatory Cairns) (anti-phlogistic), antiulcerative, wound-healing, sedative, and uterotonic activity. The flower oil (yield 0.1% essential oil33 from dried flowers) primarily contains cadinene (d-cadinene: 18-55.2%, y-cadinene: 9–25%) and ɑ-cadinol (20%), epi-ɑ-muurol (12%), ɑ-muurolene (5.6%), with smaller amounts (2–3%) of viridiflorol, ɑ-calacorene, ledene, β-ionine and y-muurolene (Gazim 2008b). 33 The Calendula oil often used for healing purposes is an infused flower oil. This analysis refers to the steam-distilled essential oil.

 Decontamination: New Uses for Old Herbs Calendula alata has been studied for the phytoremediation of cesium and lead. Plants grown in contaminated hydroponic solutions, while being reasonably effective at reducing cesium levels (41–52% removal), were much more efficient at binding lead (95–99%) (Borghei 2011). Chenopodium album and Amaranthus chlorostachys were other effective candidates for cesium phytoremediation (Moogouel 2011). A number of species of Dandelion also appear to have lead and cadmium accumulation properties that may be useful for environmental

Calendula alata is native to western Asia (Iran, Iraq) and Russia, Pakistan and India.

remediation (Wei 2010; Pichtel 2000). French Marigold (Tagetes patula) has similar cadmium accumulation and tolerance attributes (Liu 2011) – an affinity that can be enhanced by treatment with EDTA (ethylene diamine tetra acetic acid), which will also increase the chelation of zinc, copper and iron by this plant (Sinhal 2010). Conversely, wild herbs should not be harvested for medicinal use from contaminated

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sites, including roadside verges, car parking sites, industrial areas or rubbish dumps. French Marigold also has effective remediation properties for soils contaminated with the highly carcinogenic coal tar compound, benzo[a]pyrene (Sun 2011). In the eighteenth century this was the compound responsible for scrotal cancer in chimney sweeps, and in the nineteenth century was associated with the development of skin cancer among fuel industry workers. High levels are found in exhaust fumes (especially diesel), cigarette smoke, barbecue charcoal, and charbroiled foods. The potent dietary antioxidant activity of vitamin C may well have antidotal effects against this carcinogen. In addition, intriguing environmental attributes have been discovered for herbal dye wastes. An Indian study of the wastewater from Aztec Marigold (Tagetes erecta) that compared it to the wastewater from a number of other dye plants (Hibiscus rosa-sinensis, Rosa rugosa and Canna indica) revealed arsenic detoxicant (biosorbent) properties of significance (85–98% arsenic removal) – which suggests it has valuable applications for environmental remediation, with potential for use in local projects (Nigram 2012). Rice husks have similar attributes (Ranjan 2009) – as does a stem powder from Acacia nilotica (Baiq 2010).

Tagetes erecta. (Courtesy Kurt Stüber, CC-by-SA 3.0 Unported)

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Tagetes: American Marigolds

Marigold flower infusions have long been a popular stimulant with diuretic, stomachic and carminative effects. A number of species are commonly utilised medicinally, primarily Tagetes erecta, T. lucida, T. minuta, T. patula and T. filifolia.

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The genus Tagetes from North and South America has provided some versatile, highly valued remedies, that are used in a very similar manner to Calendula. These herbs have been adopted into garden cultivation across the world – indeed, the Aztec Marigold (Tagetes erecta) is also known as ‘African Marigold’, while ‘French Marigold’ refers to T. patula. A tea made from the juice or the ground leaves of Aztec Marigold has been a common appetiser, while the flower juice was widely recommended as a blood purification agent (Neher 1968). In South America Tagetes erecta has been a popular tonic stimulant, and a useful diaphoretic agent to induce perspiration in fevers. It has been utilised in treatments for body pain, sore throat, influenza, rashes, gastrointestinal distress (diarrhoea, stomachache), heart attack, arthritis – and against the ‘evil eye’ (Alonso-Castro 2012). An infusion of three flowers steeped in a cup of boiling water for 10 minutes was a simple tea preparation – or the whole plant could be decocted in two gallons of water for 10 minutes and added to a bath for children and infants with influenza, fevers or colds, and to ease general malaise, colic or diarrhoea. The decoction provided an equally useful wash for wounds, sores, abscesses and

inflammatory skin problems. Additionally, the herb has been a popular aid for gastrointestinal function (infant colic, gastric pains, flatulence), and used as a headache remedy (Arvigo & Balick 1993). Brazilian and Mexican traditions have used the decoction or infusion of Aztec Marigold extensively for respiratory problems, particularly bronchitis and lung disorders. The hot leaf poultice was applied to boils and carbuncles, or the flower juice taken as a remedy for piles (haemorrhoids). In Brazil the roots were also recommended as a laxative, while a Mexican

Mexican Tarragon (Tagetes lucida) is a good tarragon substitute in cooking. Methyl chavicol is present in extremely high amounts (95–97%) in the distilled oil of the fresh herb and imparts an anise aroma to the plant (Ciccio 2004). An analysis of the coumarin components found they had a broad spectrum of antibacterial activity, notably against gram-negative bacteria – as well as good antifungal properties. The activity of a number of coumarins (including esculetin and scoparone) against the cholera bacteria (Vibrio cholerae), which is transmitted in contaminated water supplies, was of particular interest. Certainly this tends to support the traditional use of the herb as a cure for gastrointestinal diseases. In addition, the herb has been recommended ‘to calm mental agitation’, as a hangover cure, and ‘to diminish the harsh manifestations of smoking Turkish tobaccos’ (Cespedes 2006). The herb decoction has also shown antidepressant properties (Gabriela 2012).

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anti-malarial treatment employed an ointment (based on the juice and leaves) externally to prevent chills. In addition, the herb has been incorporated into diverse remedies for liver problems, for use as a muscle relaxant, and even as an aphrodisiac potion (Neher 1968).   Tagetes patula, which is naturalised in some regions of southeastern Australia, has been similarly recommended in the folk traditions of Mexico and South America as a diuretic, stomachic, nervine and carmative remedy. It has been equally valued in the Philippines, where the flower-based infusion was taken to relieve the discomfort of colic and intestinal gas. In Colombia, Tagetes patula flower tea was used as an eyewash, while in India the leaf juice of Tagetes erecta provided eyedrops. Both species have been utilised as infusions or rubs for easing rheumatic or arthritic pain – with studies verifying their antioxidant, antiinflammatory, analgesic and anti-arthritic properties (Faizi 2011a; Bashir & Gilani 2008; Kasahara 2002; Neher 1968). Studies have also shown Tagetes patula root extracts have hypotensive activity, which was attributed to citric and malic acids, while the pyridine hydrochloride component had a hypertensive effect (Saleem 2004). Interestingly, Tagetes patula and T. erecta earned a good reputation for the treatment of bunions and corns. They have been considered particularly useful for verruca (warts), fungal nail infections and a condition known as hallux abducto valgus (a deviation of the big toe toward the outer side of the foot). Verruca lesions are characterised by a thickened and heavy callus that causes irritation, inflammation and pain. Clinical studies have shown that the remedy had an analgesic effect and was effective for reducing the size of the growth (Khan 1996a, 1996b).   The essential oils of Tagetes minuta and T. patula flowers have significant antifungal properties. The latter contains piperitone (24.7%) and piperitenone (23%), as the main components – with smaller amounts of terpinolene (8%), dihydro tagetone (4.9%), cis-tagetone (4.6%), limonene (4.5%) and allo-ocimene (3.7%) (Romagnoli 2005; Bii 2000). Herb extracts have equally valuable antifungal properties, with a thiophene constituent (ɑ-terthienyl) possessing substantial activity against the dermatophytes associated with skin infections (Mares 2004; Romagnoli 1994). Tagetes minuta flower oil also possesses antifungal properties.

     

Marigold Carotenoids

Tagetes erecta.

Aztec, Mexican or African Marigold (Tagetes erecta) has considerable commercial value as a carotenoid resource. It provides a yellow dye suitable for use as a food colouring, particularly for butter and cheese.34 Xanthophylls and carotenoids from the flowers have demonstrated antimutagenic, antioxidant, and anticarcinogenic properties that enhance its usefulness as a food additive (Breithaupt 2002; Brazana 2001; Gonzalez de Mejia 1997; Chew 1996; Neher 1968). Lutein (a xanthophyll pigment) is of particular interest due to its significant therapeutic potential, notably as an antioxidant, immune stimulant and anticancer agent. In particular, lutein has shown protective potential in colon and breast cancer cells. Lutein, as well as another yellow carotenoid pigment, zeaxanthin, accumulate in the retina of the eye and have been linked to a protective effect against age-related macular degeneration and cataracts. Both conditions can result in blindness. The lutein in Marigold oleoresin extracts is bioavailable, with dietary supplementation showing a five-fold increase in serum lutein levels (Chew 2003; Olmedilla 2002, 2003; Evans 2002; Slattery 2000; Hadden 1999). 34 See Cantrill (2004) for technical details of extraction and use.

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Garden Nasturtium (Tropaeolum majus). Nasturtium flowers and uncooked kale (a type of cabbage) contain particularly high levels of lutein. Other dietary resources of importance include ‘greens’ such as dandelion, nasturtium leaves, spinach, swiss chard and turnip greens. It is also found in zucchini, broccoli, brussells sprouts, garden peas, lettuce, tomatoes, oranges (including the juice) and celery – with lower levels being present in corn, carrots, eggs and kiwifruit. (Image courtesy J Busson CC-by-SA 3.0 Unported)

Stinking Roger: An Insecticidal Import

Stinking Roger (Tagetes minuta) has an equally diverse therapeutic reputation as the Tagetes species already discussed. The flowers were used in Argentinian folk medicine as an aperient, diuretic and diaphoretic remedy. It was popularly taken for gastrointestinal disorders (indigestion, gastritis), and as a mild laxative. The whole-plant decoction was recommended as a stomachic (to strengthen stomach function), as a general stimulant, as a sedative for hysteria and to promote menstrual flow. It was, however, also reputed to have purgative potential (Neher 1968). The Khaki Bush was imported into Australia by troops bringing it back after the African Boer Wars in the late 1800s. In Africa, where it was already naturalised, it was widely used for the treatment of infected wounds, chest infections (inhaled as an antiseptic agent, to dislodge mucous, and open the airways) and foot problems (bacterial or fungal infections, growths such as calluses and bunions). It

Stinking Roger (Tagetes minuta) is an introduced South American weed with antiparasitic and insecticidal properties. The crushed leaf has a particularly strong aroma, albeit not necessarily pleasant, hence the common name. Unfortunately, handling the herb can result in skin and eye irritation in sensitive individuals and wounds may turn septic. Moreover, it is not suitable for use as grazing fodder for cows as it imparts a highly disagreeable flavour to milk, cheese and butter products (Neher 1968).

has good antiseptic, antibacterial and antispasmodic properties. However, it should be avoided by those sensitive to the Asteraceae as its use has been linked to photosensitivity and skin reactions (dermatitis).35 The aromatic oil of Tagetes minuta has excellent insecticidal activity, particularly when combined with pyrethrum. An old recipe for killing maggots in wounds, which was said to be highly effective, combined carbon tetrachloride, wool fat, 5 per cent Tagetes oil, water and a preservative to make an emulsion. Even in 1926 the herb was regarded with 35 ɑ-terthienyl has been suggested as the phototoxic component of Tagetes oils. See SCCP (2005) for further details.

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some interest, as Professor Rennie commented: There is yet another oil to which I should like to refer though it is derived from a plant not indigenous in Australia, namely, Tagetes glandulifera [T. minuta], which has become naturalised in Queensland and flourishes vigorously in the coastal districts of that State. In the flowering season it gives out a powerful and unpleasant odour, and it is chiefly from the flowers that the oil has been obtained. T. G. H. Jones, of the University of Queensland, has very carefully examined this oil and finds that in addition to terpenes, 30% ocimene, and 4% limonene, it contains two closely related olefinic ketones … having the same assemblage of carbon atoms as in citral and citronellal and which have not yet been found in essential oils. One of these ketones is remarkable (it has been called tagetone) in respect of its rapid absorption of oxygen and consequent resinification on exposure to air, a property which makes its isolation and investigation a matter of no small difficulty. It also possesses other remarkable characteristics.

The insecticidal properties of Stinking Roger have an extremely practical reputation. In Africa the plant was hung in doorways to repel flies, put in mattress stuffings as an insecticide, or planted in gardens to deter ants, bugs and mites. Various preparations (plant juice, or an oil from the leaves, flowers and seeds) were applied externally as a blowfly deterrent on animals, or the herb used to treat parasites in cattle.36 Studies have shown that the flowers had good mosquitorepellent activity, while the leaves were somewhat less active. Tagetes minuta was potently effective as a mosquito larvicidal agent, with T. patula exhibiting less activity. The effect was attributed to thiophene derivatives, compounds that are present in many of the Asteraceae. Other species with insecticidal and insect repellent activity include Tagetes filifolia, T. rupestris, T. subulata and T. erecta – with the latter showing activity against the mosquito Anopheles subpictus (Elango 2011; Lopez 2011; Seyoum 2002; Margl 2001; Broussalis 1999; Macedo 1997; Perich 1995, 1994; Sharma & Saxena 1994; Saxena 1992; Green 1991; Cribb & Cribb 1981). The essential oil of Aztec Marigold (Tagetes erecta) 36 Chamomile oil has also shown insecticidal activity against larvae of the blowfly (Lucilia sericata) responsible for myiasis (parasitic fly infestations). Lettuce (Lactuca sativa) oil was equally effective (Khater 2011). Chamomile oil also had good fly-repellent and moderate lice-killing (pediculicidal) properties against these pests of water buffalo in Egypt (Khater 2009). In addition, Chamomile flower extracts were strongly acaricidal against mites (Psoroptes cuniculi) (Macchioni 2004).

87 Tagetes minuta essential oil is sourced from the leaves stalks and flowers of the plant, just as the seeds are beginning to form. (Courtesy essentialoils.co.za)

was also larvicidal against the malaria and yellow fever mosquito vector Aedes aegypti – with investigations establishing that the roots and flowers had higher concentrations of the active thiophene components. The oil was piperitone rich (45.7%), with lesser levels of piperitenone (5.9%) and D-limonene (9.7%) (Marques 2011). Tagetes erecta root extracts have also shown good antibacterial and antifungal properties, as well as antiplasmodial activity against the malaria parasite Plasmodium falciparum (Gupta & Vasudeva 2010). Tagetes minuta and T. lucida (from Mediterranean sources) were found to have a good thiophene content, suitable for development as a biocidal crop with pest control attributes (Marotti 2010). Stinking Roger has even been grown in tobacco fields to discourage crop pests, notably root-knot nematodes. However, attempts to use the herb on a practical basis in California failed as its weedy habit overtook the crop. It was also virtually impossible to control its spread in irrigated groves. Tagetes erecta and T. patula, which have shown a similar resistance to nematode attack, have been used as a cover crop in Indian Tea plantations. They could demonstrably decrease the incidence of a pest known as the meadow eelworm (Pratylenchus pratensis). ɑ-terthienyl was identified as the nematicidal agent, which also had interesting photobiocidal properties with potential for use as a light-activated insecticide (Nivsarkar 1996; Neher 1968; Cribb & Cribb 1980; Webb 1948). Flower extracts of Tagetes patula have shown excellent nematicidal activity against the corn cyst nematode (Heterodera zeae), which was attributed to the phenolic components (flavonoids, phenolic acids) and ɑ-terthienyl (Faizi 2011b). Doubtless many other crops could benefit from the inclusion of these herbs in the fields.

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Aromatic Native Asteraceae

Pterocaulon sphacelatum. Niemenski, flickr)

An Australian species of the Asteraceae that also goes by the name of Stinking Roger (and Smelly Bush) is Streptoglossa odora (formerly Pterigeron odorus37) – a small herb of the inland spinifex regions in the northern tropics. Streptoglossa bubakii and S. decurrens have a comparable medicinal and aromatic reputation. Aboriginal people used the aromatic crushed leaves to make a decongestant decoction that was applied externally as a wash for the relief of influenza, head and chest colds, and headache. It has also been utilised as a plug of rolled leaves inserted in the nose, or the crushed herb (or infusion) inhaled. The herb, crushed on a stone and firewarmed, then placed on the chest, was regarded as being equally effective (Pearn 2005; Latz 1996; Wrightman 1994; Barr 1993; Smith 1993).     These herbs contain essential oils with insect repellent properties. Extracts of Streptoglossa bubakii have fly-repellent activity and the oilrich leaf (essential oil level: 10–15% dry weight) contains caryophyllene and y-elemene (Pearn 2005; Southwell & Maconachie 1977). Other samples have given a lower essential oil yield (0.3%), albeit the main components were the same (Barr 1993). Smelly Bush leaf, as well as the caustic latex, has been used on scabies sores to relieve itching (Isaacs 1994; Lassak & McCarthy 1992). In the Northern Territory a few of species of Pterocaulon have a similar reputation for 37 In Australia the genus Pterigeron has been reclassified as Streptoglossa, which contains eight species. They are primarily found in northern Australia, although a couple of species range to New South Wales and/or South Australia.

(Courtesy

Craig

Stemodia viscosa (Scrophulariaceae). (Courtesy Dave Rentz, flickr)

the treatment of respiratory and skin problems – notably P. globuliflorus, P. serrulatum and P. sphacelatum (these Asteraceae herbs are discussed in greater detail in Chapter 3). Stemodia viscosa has been held in similar regard to Pterocaulon as a decongestant remedy. The fresh leaves were inserted into the nostril or the powdered dried leaf utilised a snuff. A lotion, prepared from the dried leaf decoction, was also considered useful for treating conjunctivitis or skin sores (Barr 1993).

 While the Asteraceae family contains many herbs of enduring therapeutic value, there are numerous other plants of medicinal importance that are native to these shores. The emphasis has been on tonic and wound-healing remedies, particularly for the treatment of bacterial disorders. Among the microbes responsible for bacterial infections, the Mycobacteria have been of special importance, primarily because

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these infections were so difficult to treat. This classification was responsible for the hideous scourge of leprosy and the chronic wasting associated with tuberculosis. Indeed, these conditions were highly unresponsive to most treatments until the advent of antibiotic drugs. However, a limited number of the herbal remedies that were used did have valid therapeutic effects – and have continued to be of interest for a number of different reasons, not least because of the advent of antibiotic-resistant bacteria and the prevalence of side-effects from antibiotic drugs.

In country areas most Australian households would have had a stock of remedies in the bathroom or kitchen cabinet that could be used for ‘just about anything’ – although ‘bush remedies’ were more convenient for travellers, particularly the bushmen and stockmen who worked around the countryside. Eucalypt Kino (left) was probably one of the most well known and widely available of the antiseptics, although the distillation of Eucalyptus oil in commercial quantities quickly saw it become an indispensible addition to the medicine cabinet.

Chapter 3

VALIDATING BUSH MEDICINES level of self-sufficiency. Sir James Robert Price and colleagues (1993) outlined the situation: ‘During the war [1939–45], serious thought had to be given to finding new sources for the essential drugs and other substances, such as vitamins, insecticides and insect repellents, which were significant for the health and competence of combatant troops. Although synthetic organic chemistry was making a rapidly growing contribution to the medical inventory, many essential drugs were still of plant origin (as many still are) and were largely imported from overseas.’   These circumstances inspired attempts toward a more comprehensive evaluation of the phytochemical properties of the native flora – a venture that was to become a herculean biochemical task. The initial investigations during the war had:

The development of Australian Eucalyptus oil as a household antiseptic and decongestant has certainly been the most outstanding and enduring achievement of therapeutic importance from this continent. However, the cultivation of the Eucalypt as an oil and timber resource was an enterprise that quickly dispersed across the globe. Indeed, China is now the major supplier of Eucalyptus oil on the international market. (Image courtesy Felton Grimwade & Bosisto’s Pty Ltd)

made evident the need for a systematic survey of pharmacological potential. So, in 1944, the CSIRO Division of Plant Industry planned such a survey to involve botanical, pharmacological and chemical collaboration. With one or two exceptions ... background pharmacological information was almost negligible. The starting point of the programme, therefore, was a preliminary botanical survey in the hands of Dr. L. J. Webb [published 1948 and 1952]. This soon revealed that the volume of chemical work would be far beyond the capacity of the chemists available, so the co-operation of the universities was sought, [particularly] those interested in natural product chemistry (Price 1961).

Despite the fact that native plants were utilised medicinally since the arrival of the First Fleet, in the long term most of the Australian flora gained little currency as medicinal or economic resources. Surprisingly enough, World War II was to have a major influence on the development prospects for Australia’s natural resources, fostering a dramatic change in attitude. The war effort unexpectedly highlighted the pitfalls of an exclusive reliance on overseas drug supplies. Serious shortages of medicines on the international market pressed home the point that Australia had neglected resources with phytochemical potential. These were sorely needed if this country was to achieve any

Over time, an extensive evaluation of the flora resulted. Although much was achieved, it has been an undertaking that continues to this day. It was a difficult, timeconsuming and, at times, seemingly impossible task to sort through the preliminary floral identification and chemical requirements of the project. 90

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Native Antibacterials

Many plant-based remedies that provide successful folk medicines rely upon an effective antimicrobial action. Antibacterial activity has always been a vital component of remedies selected for general first aid and wound healing purposes. Therefore, it was logical that an evaluation of this aspect of the native flora attracted substantial attention and this became a serious post-war chemical challenge in the 1940s. When Howard Florey initially described penicillin ‘as a chemotherapeutic agent’ very little was known about the chemical potential of natural products. His discoveries were to inspire a colossal amount of interest across the world, which directly filtered through to the Australian scientific community. An early Australian report on Queensland plants tested against Staphylococcus aureus reviewed extracts prepared from 158 species belonging to 150 different flowering plant (angiosperm) families (Talcott & Webb 1948). Only four were found to have appreciable activity against Staphylococcus aureus – a common cause of food poisoning and infection. These were extracts of Canthium oleifolium (now Psydrax oleifolia; leaves), Crotalaria incana (leaves), Eugenia [Syzygium] smithii (leaf and mature fruits) and the naturalised Moluccella laevis (leaf and stem). The authors commented: ‘This is apparently the first record of Australian plants with antibacterial activity … belonging to the families Labiatae, Leguminosae, and Rubiaceae, and the genus Eugenia.’

Syzygium smithii (formerly Acmena smithii) is a native Lillypilly found in Queensland, New South Wales and Victoria. It may also occur in Tasmania. (Courtesy Melburnian)

Moluccella laevis is naturalised throughout much of the Australian continent – although it does not favour the tropics and is not found in the Northern Territory. (Courtesy Tsiaojianlee, Public Domain, Wikipedia)

Canthium oleifolium (now Psydrax oleifolia) is found in New South Wales and southern Queensland. (Courtesy Paul Campbell)

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bacilli, staphylococci and the acid-fast Mycobacterium phlei’ (Cleland 1950). Studies determined that the antibacterial activity of Geebung fruits could vary substantially. This was an important consideration that led to more detailed investigation. It was established that the very young or very old berries from Persoonia pinifolius had little effect against bacteria. The main activity was located only in the fleshy part (i.e. the juice extract) and peaked in mature fruits that were developing from green to purple. The results were significant: ‘[even] after drying and storage for several months berries still retained activity; which was stable and watery extracts remained active for at least 6 months’ (Atkinson 1949). Persoonia salicina and P. falcata berries were likewise found to be active. Unfortunately, the conclusion was that ‘Our Persoonia antibiotic may prove too toxic for chemotherapy except perhaps for local application where its ability to inhibit Pseudomonas pyocyanea and many common bacteria may be useful’.

The Woolly Rattlepod (Crotalaria incana) is a fairly widespread weedy species that is found throughout most of the Australian continent. (Courtesy Kim & Forest Starr, Hawaii)

Flowers of Crotalaria incana. (Courtesy Carlos Ivovic, flickr)

A massive review of the antimicrobial properties of the Australian flora was to follow. An important project initiated by Dr Nancy Atkinson and her team was to ultimately evaluate more than 1,200 plants. Dr J Burton Cleland reviewed these advances: ‘Many of the available native flowering plants were examined and it was found that an extract of the fruits [of one] of the Proteaceae, the Geebung, Persoonia juniperina, exerted an antibiotic effect on typhoid

Persoonia pinifolia. (Courtesy Dr David Midgley)

VALIDATING BUSH MEDICINES

Persoonia pinifolia. (Courtesy Melburnian)

  Milky Plum: Sacred Medicinal Plant The Milky Plum, Persoonia falcata, is a fairly widespread species throughout tropical Australia. In Queensland it ranges south to the central coast, extending into a drier inland climate. Milky Plum, which was widely employed as an antibacterial remedy in the Northern Territory and Queensland, was regarded as being a particularly good treatment for earache or infected eye problems (conjunctivitis). An infusion of the white inner bark scrapings, mixed with breast milk and water, could be easily utilised as ear and eye drops (Yirrkala Community School, 1990). Additionally, the bark has anti-diarrhoeal and expectorant properties. A leaf decoction, or the leaf simply chewed and the juice swallowed, was also highly regarded as a remedy for coughing, sore throat,

The Milky Plum (Persoonia falcata) is sacred to some Aboriginal tribes. It is considered to be a particularly powerful plant with an important role in magic ceremonies – including rites executed with harmful intent. It was reputed to inflict pain, and was even said to cause death if the magic was strong enough (Levitt 1981).

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oral thrush (candidiasis) or diarrhoea. In chest infections (including tuberculosis) it was used to loosen phlegm and promote its expectoration. The wound-healing properties of the leaves have even been utilised to heal circumcision incisions (Brock 1993; Barr 1988; Cribb & Cribb 1981).

Desert woomera. The tough wood of the Milky Plum was widely used to make spear-throwers (woomeras), boomerangs, axe-handles and music sticks. The bark contains approximately 9 per cent tannin. This could be soaked in water to make a preservative liquid for string or fishing lines, a process that increased durability. (Image courtesy Collection MB Abram Galleries, Los Angeles)

 

Persoonia falcata fruit. (Courtesy SGAP, Townsville)

Geebungs have been valued as a snack food wherever these trees were found. The genus contains 105 species, most of which produce small edible fruits favoured by Aboriginal people throughout the continent – although there is fierce competition from a wide range of wildlife, including kangaroos, rats, emus, smaller birds and the voracious feral pig. The small amount of flesh on the fruit has been described as tasting like sweet cotton-wool.   Its popularity was mentioned in Tom Petrie’s Reminiscences of Early Queensland: ‘The fruit of the geebung [Persoonia], or “dulandella”, as the Brisbane tribe called it, was eaten raw, and greatly relished. The natives got dillies full of these in the right season. They swallowed the pulp and the stone, which they squeezed from the skin with their fingers. It is a small green fruit.’   Joseph Maiden recorded in his notes that: ‘These fruits are mucilaginous, insipid, and slightly astringent. They are largely consumed by aborigines, and also to some extent by small boys. Geebungs when dead ripe have a flavour which may be compared to that of apples, but the flesh is very stringy, and they have very big stones’ (Maiden 1888a).

The Geraldton Wax Plant (Chamelaucium uncinatum)

Geraldton Waxflower.

Chamelaucium is a small genus, endemic to Western Australia, that contains around a dozen species. The Geraldton Wax or Waxflower (Chamelaucium uncinatum) is the most familiar as it has been widely adopted in the ornamental

VALIDATING BUSH MEDICINES

plant trade. The investigations of Dr Nancy Atkinson in the 1940s listed this species among the numerous plants whose medicinal potential was virtually unknown: ‘[the] Crude oil from the flowers of the Geraldton Wax plant (Chamelaucium uncinatum) was also found to possess antibiotic properties’ (Cleland 1950). The leaves have a pungent quality and were used by Aboriginal people to make a mouthwash. Analysis of the essential oil of the leaf has identified four chemotypes (Egerton-Warburton 1998): •  Citronellal (55.36%): with lower levels of α-pinene (15.55%), geraniol (6.36%), limonene (4.93%), and α-terpinyl acetate (5.56%); • Limonene (49.91%): with α-pinene (27.04%), and low levels of citronellal (3%) and α-terpinyl acetate (3.23%); • α-pinene (54.07%): with limonene (12.85%), some citronellal (7.11%) and α-terpinyl acetate (4.83%); • Another oil form contains all three monoterpenes: citronellal (12.12%), limonene (23.98%) and α-pinene (22.95%), with lower amounts of linalool (4.73%) and α-terpinyl acetate (8.01%).

Bush Flower Essences are primarily utilised as emotional and spiritual healing remedies. There are many to choose from and the wildflowers of Western Australia have had a prized place in their development. Geraldton Wax Bush Flower Essence has been used as a remedy to balance the mind and emotional state. (Images courtesy Solara Antara, flowersforhealing.com)

There are a few other components of interest: • A  ll four oil types contain small amounts of β-pinene (0.79–2.11%), globulol (1.98–3.12%), 1,8-cineole (1.17–2.14%), linalool (0.91–4.73%), geraniol (1.13–6.36%). • B  orneol and α-terpinolene were present at low levels (3.13% and 2.03% respectively) in the citronellal-based oil.

There are a few species of Chamelaucium that have not yet been classified botanically – and the genus Verticordia, the ‘feather-flowers’, is very closely related – with V. brownii, V. plumosa and V. verticordina originally classified as Chamelaucium. The Pink Brownii or Pink Cauliflower (Verticordia brownii) has the particular distinction of being named after the famous botanist Robert Brown. It was one of the first of the genus collected by European botanists, being placed in Verticordia by the Swiss botanist Augustin Pyrame de Candolle, who established this genus in 1828.

Verticordia brownii. (Courtesy William Archer, esperancewildflowers.blogspot.com)

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Pterocaulon: A Fragrant Wound Remedy

A number of interesting candidates for antibacterial evaluation come from the Pterocaulon genus (Asteraceae family), many of which have distinct fragrant attributes. The Fruit-salad Plant or Applebush (Pterocaulon sphacelatum) and P. serrulatum (syn. P. glandulosum)1 have a good reputation in traditional Aboriginal medicine as decongestant and antiseptic remedies. The highly aromatic leaves were utilised as an inhalant or ‘rubbing medicine’ for treating colds, coughs, headache and fevers – particularly influenza. Although the herb was not usually taken internally, it has been popularly applied as a decongestant liniment on the chest, similar to Vicks VapoRub, for respiratory disorders (bronchitis, pleurisy). The sticky leaves can be simply crushed and inserted into the nostrils to clear the head or to relieve sinus congestion. Pterocaulon serrulatum, which is said to be among the more aromatic members of the genus, possesses insect-repellent properties – and has therefore been employed as a fumigant in campfires and as a mosquito repellent applied to the skin. The wash was also useful for healing sores or wounds, as well as eye inflammation (Latz 1996; Barr 1993). The healing attributes of Pterocaulon serrulatum were considered efficacious for spear injuries. FS Colliver (1972) commented: ‘the leaves of Pterocaulon glandulosus are used for stuffing up and rubbing over spear wounds in the arms and legs by the Koko-minni people and the charcoal from the wood of Grevillea striata is used to stop the haemorrhage in certain spear wounds’. Len Webb mentioned that the leaf

was potent only when green, and that an overdose could stimulate the heart (Webb 1948). The latter is interesting, as Vietnamese studies have shown that a flavonoid component, chrysosplenol C, has experimental cardioactive properties (Son 2011). Various species have been examined for antimicrobial properties and it appears that antifungal activity may be quite widespread in the genus. Argentinian investigations isolated flavonoids with antibacterial activity from Pterocaulon alopecuroides (Alarcon 2008). Brazilian studies of its potential as an antifungal agent determined activity against chromoblastomycosis, a chronic fungal skin infection (Daboit 2010). Other South American studies indicate that extracts of Pterocaulon alopecuroides, P. balansae and P. polystachyum have excellent antifungal potential. In particular, Pterocaulon polystachyum demonstrated activity against Cryptococcus neoformans

Pterocaulon serrulatum. (Courtesy Craig Nieminski) 1 There are a total of seven native Australian species. In addition to the above, they are P. globulus, P. nivens, P. redolens, P. spheranthoides and P. verbascifolium.

Pterocaulon polystachyum, from Flora Brasiliensis, Vol. 6/3, 1882.

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(a fungal yeast that can cause meningitis) and various common dermatophytes (Microsporum gypseum, Trichophyton rubrum, T. mentagrophytes) responsible for skin infections (Stein 2006, 2005). In addition, this species has antioxidant, cytotoxic and experimental anticancer (anti-leukaemia) properties (Silveira 2009; Knoll 2006; Riveiro 2004; Mongelli 2000). Pterocaulon polystachyum, which has also been used for the treatment of digestive disorders, has been evaluated for antiparasitic properties. Plant extracts showed activity against the amoeba responsible for acute amoebic keratitis, Acanthamoeba castellanii. Extracts active against the parasite (66–70% lysis of trophozoites) were also able to prevent cyst formation, which is a significant obstacle to effective treatment of the condition (Rodio 2008). The leaf essential oil2 showed similar effects against Acanthamoeba polyphaga. However, it was not suitable for direct use – although the oil did have practical potential. Its incorporation into contact lens cleaning solutions was suggested for the prevention of amoebic contamination, which commonly results in keratitis – a very painful inflammatory condition of the cornea that can lead to impaired eyesight due to corneal scarring (Sauter 2011). While the herb requires further evaluation to establish its clinical usefulness, initial studies did not suggest that there were serious toxic concerns (Regner 2011). Pterocaulon sphacelatum is a native Australian medicinal herb with anti-mycobacterial potential (Meilak & Palombo 2008) that has also attracted interest as an antiviral agent. Extracts showed antiviral activity against poliovirus, with the isolation of a flavonoid (chrysosplenol C)3 that was active against picornaviruses (Semple 1999, 1998). A couple of related South American species have similar antiviral potential. Pterocaulon polystachyum demonstrated activity against Herpes simplex that appeared to be linked to coumarin components. Similar compounds were attributed with the antiviral (anti-HSV) activity of Pterocaulon alopecuroides extracts – which also possessed significant antioxidant and cytotoxic properties (Silveira 2009). 2 An uncommon compound, E-sesquilavandulyl acetate (43.8%), was identified as the major component in the oil, with smaller amounts of E-sesquilavandulyl (17.3%), β-caryophyllene (10%), ɑ-copaene (5.4%) and germacrene D (3.4%) (Sauter 2011). 3 Chrysosplenols B and C have also been isolated in other medicinal plants, e.g. Miliusa balanse (Son 2010; Huong 2005).

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Pterocaulon sphacelatum. (Upper image courtesy Craig Nieminski, flickr)

Interestingly the Brazilian plant Acanthospermum australe, which was also found active against Herpes virus, contained chrysosplenol D – as well as the flavonoid quercetin (Rocha Martins 2010). Chrysosplenols have attracted further interest because they have the potential to increase the efficacy of some antibiotics and antimalarial drugs (Kraus & Roy 2008). For instance, chrysosplenol D and chrysoplenetin from Artemisia annua demonstrated a very weak antibacterial (growth-inhibitory) action against drugresistant Staphylococcus aureus. This was significantly potentiated with the addition of berberine.4 These flavonols were also reported to potentiate the activity of artemisinin (an antimalarial drug sourced from Artemisia annua) against Plasmodium falciparum (Stermitz 2002). 4 Berberine is an exceptionally important alkaloid that is found in diverse plants – notably the genera Berberis, Hydrastis and Coptis, a number of which are valued herbs in Chinese medicine and Western herbal traditions. Berberine (and related isoquinoline alkaloids) have significant antimicrobial (antibacterial, antifungal), anticancer, neuroprotective, antidiabetic, antiinflammatory, antioxidant and cardiotonic properties.

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Chrysosplenol D is among the flavonoids isolated from the antimalarial herb Artemisia annua. (Courtesy Lloyd Crothers)

Chrysosplenol D, isolated from Vitex negundo var. cannabinifolia, exhibited activity against a number of food spoilage microorganisms (Escherichia coli, Bacillus subtilis, Micrococcus tetragenus, Pseudomonas fluorescens) (Ling 2010). Vitex trifoliata, which is one of the ten native Vitex species found in Australia, also contains this flavonoid. In the Northern Territory some Aboriginal tribes utilised an infusion of the pounded leaves as a wash for scabies and other itchy skin conditions (Barr 1993). Recent studies have taken an interest in the anticancer potential of chrysosplenol D and a related flavonoid, chrysoplenetin (Awale 2011) – which provides an interesting link to the Chinese folk medicine use of Vitex trifolia for the treatment of cancer (Li 2005).

Plectranthus: Aromatic ‘Native Mints’

Vitex trifoliata.

Vitex negundo. (Courtesy Dinesh Valke)

The genus Plectranthus is fairly large, containing over 300 species that range from Africa to India and Australasia – of which 42 are found in Australia. These herbs belong to the Lamiaceae, a family that contains many popular aromatic culinary herbs such as Basil (Ocimum spp.), Sage (Salvia spp.) and Mint (Mentha spp.). A number of aromatic herbs in this family have a great deal of similarity in their appearance – which has, at times, proved a significant obstacle to their classification. The genus Plectranthus is no exception.5 Various species have been identified as Coleus – although they have often been well placed in the closely related genera Anisochilus, Englerastrum, Solenostemon, Tetradenia and Isodon. Substantial debate regarding the classification of numerous species continues. Understandably, this has made their definitive botanical classification difficult, resulting in various discrepancies and diverse name changes in the literature. Biochemical studies may be of some value in solving these dilemmas. Recently, flavonoids in exudates from various species have been examined with the aim of clarifying the relationships within the Plectranthus genus (Grayer 2010).

5 The ‘Native Mints’ (genus Prostanthera) are also in Lamiaceae (see Volume 1).

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‘Variegated Mint’, Plectranthus madagascariensis. (Courtesy Kim & Forest Starr, Hawaii)

The genus Plectranthus has interesting antimicrobial potential. Even though little is known about the chemistry of the native Australian species, these plants have been employed in the traditional medicinal practices of tropical Africa, Asia and South America – mainly as healing agents for burns, injuries, sores, insect bites and allergic skin reactions. Indeed, more than 60 species have been recorded as possessing medicinal or economic value (Lukhoba 2006). This indicates that the native herbs could certainly be worthy of more intense scrutiny. Unfortunately, knowledge regarding their medicinal use in Australia is sparse – possibly because this was never recorded, and not because they remained unused. Walter Roth (1903) noted that an infusion of a tropical Queensland Plectranthus congestus (leaf and branchlets) was employed for ‘internal complaints’. This is a rather unusual recommendation as few herbs were taken internally by Aboriginal people. The leaves of this species have been applied as an antiseptic dressing for wounds in Papua New Guinea, which suggests antibacterial potential. It was also said to be useful for treating the parasitic skin condition scabies (Woodley 1991; Holdsworth 1977). Certainly a number of native species have shown strong acaricidal activity against the horticultural pest, red spider mite (Tetranychus urticae; see Table 3.1), which suggests these plants could have more extensive insecticidal potential.6

6 Coleon A from Plectranthus saccatus has shown strong antifeedant activity against the African/Egyptian cotton leafworm (Spodoptera littoralis), a significant crop pest (Wellsow 2006).

The common garden Coleus (Plectranthus scutellarioides, syn. Solenostemon scutellarioides) has innumerable colour variations. This herb was among the species collected in Australia by Robert Brown in 1810 and placed under Ocimum scutellarioides. The herb is found throughout northern Australia (Queensland, Northern Territory and Western Australia), ranging along the Queensland coast to Brisbane. (Images courtesy Kim & Forest Starr, Hawaii)

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The Plectranthus genus is rich in essential oils, thus it is unsurprising that a number of native Australian species have distinctive fragrant characteristics. They include P. argentatus, P. parviflorus and P. graveolens. The latter was collected by Joseph Banks and Daniel Solander at the Endeavour River in northern Queensland – in addition to P. apreptus, P. foetidus and the related species Teucrium argutum. Samples of Plectranthus parviflorus were collected from Botany Bay. (Upper image courtesy Kim & Forest Starr, Hawaii; lower image courtesy Melburnian)

A couple of Plectranthus species have gained prominence as Asian medicinal herbs – P. amboinicus and P. barbatus. Their traditional uses provide some interesting insights into the pharmacological potential of the genus. Plectranthus amboinicus has been recommended for respiratory problems, feverish conditions, and infections (including meningitis).

Plectranthus barbatus was similarly taken for respiratory tract disorders and diverse infections (Lukhoba 2006). These species have demonstrated antibacterial and anti-inflammatory properties that would certainly support their traditional use. Studies of Plectranthus amboinicus indicate an interesting range of activity: antifungal, antiprotozoal (antimalarial, anti-giardia), diuretic, anti-mycobacterial, bronchodilatory and anti-tumour – as well as antiviral activity against HIV and Herpes simplex-1 (HSV-1). Plectranthus barbatus also has anti-HIV properties, as well as valuable hypotensive and spasmolytic attributes (Patel 2010; Lukhoba 2006; Matu & van Staden 2003).

The aromatic qualities of Plectranthus amboinicus have resulted in a variety of common names such as Mexican Mint, Spanish or Mexican Thyme, Cuban Oregano and Indian Borage. Interestingly, there are old Thai drug recipes that included Plectranthus amboinicus in treatments for venomous bites – and it has shown activity as an antidote against scorpion venom (Uawonggul 2006). In Queensland, this species is found as an introduced ornamental around the south coast (Gold and Sunshine Coasts) – and is also found around Sydney in NSW. (Image courtesy Kim & Forest Starr, Hawaii)

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Table 3.1 Summary of Traditional Uses of Medicinal Plectranthus Species Plectranthus amboinicus (syn. Coleus amboinicus) Synonyms: Coleus aromaticus Plectranthus aromaticus

Traditional uses (source references Waldia 2011; Lukhoba 2006) and investigations (as per reference cited) India and Africa: utilised as a remedy for diverse digestive disorders (indigestion, dyspepsia, diarrhoea), and employed as a carminative (relieve flatulence). Chinese medicine: cough, fevers, sore throat, mumps, mosquito bites (Chiu 2012). Heart: recommended for the treatment of congestive cardiac failure. Feverish conditions and infectious disorders (including cholera and meningitis). Neurological problems (including epilepsy, convulsions); extracts have shown antiepileptic activity (Buznego 1999). Respiratory problems: chronic coughing, whooping cough, asthma, bronchitis, pharyngitis, catarrhal congestion. Genitourinary tract disorders: kidney troubles, vaginal discharge, used after childbirth. Skin disorders: applied to burns, poultice for centipede and scorpion bites in Malaysia; skin ulceration associated with leishmaniasis in Brazil (Franca 1996) Note: There is a report of leg ulceration due to the use of this herb. This was attributed to allergic contact dermatitis, suggesting some individuals may be sensitive to the plant (Chang 2005). Antiparasitic: studies have confirmed the activity against Leishmania, although Plectranthus grandis extracts were significantly more active against L. amazonensis (Tempone 2008). Essential oil: mosquito larvicidal activity against malaria vector Anopheles stephensi (Senthilkumar & Venkatesalu 2010). In vivo studies of antimalarial (antiplasmodial) activity of leaf extracts showed reduced levels of parasitaemia in mice (Periyanayagam 2008). Note: Essential oil constituents: carvacrol (28.65%), thymol (21.66%), α-humulene (9.67%), undecanal (8.29%), γ-terpinene (7.76%), ρ-cymene (6.46%), caryophyllene oxide (5.85%), α-terpineol (3.28%) and β-selinene (2.01%) (Senthilkumar & Venkatesalu 2010).

Plectranthus barbatus (syn. Coleus forskohlii) Synonyms: Coleus kilimandschari Coleus coerulescens Coleus barbatus Plectranthus forskohlii Plectranthus kilimandschari Plectranthus grandis

ENT: acute oedematous otitis (ear infection); extracts have shown good activity against Staphylococcus aureus (Nogueira 2008). Eye disorders: conjunctivitis. Anti-inflammatory, anti-arthritic: used for inflammatory disorders and swelling in Taiwan; anti-arthritic activity demonstrated with potential for use in combination drug therapy (Chang 2010, 2007). Anti-inflammatory and analgesic properties shown for aqueous herb extracts; high levels of the anti-inflammatory agent carvacrol (1.88 mg/g extract) were isolated (Chiu 2012; Ravikumar 2009). Extracts have shown anti-inflammatory and protective effects against bone destruction (Hsu 2011). Antitumour and anti-inflammatory activity for leaf extracts. Used as an anticancer remedy in Brazil (Gurgel 2009). A diterpene (coleon U) isolated from Plectranthus grandidentatus has shown antiproliferative effects on several human cancer cell lines (Coutinho 2009). Coleon U also has substantial antibacterial properties and moderate antifungal activity. Coleon A has antibacterial properties to a lesser extent (Wellsow 2006). Antidiabetic and cholesterol-lowering properties: hypoglycaemic and antihyperlipidaemic effects involving restoration of pancreatic tissue function and insulinotropic effect (Koti 2011; Viswanathaswamy 2011). Kidney protective: traditional use for treating renal calculi (Koti 2011); ethanol extract showed nephroprotective and antioxidant activity, plus strong diuretic effect in animal studies (Palani 2010). Respiratory tract disorders (infections of the throat and mouth, tonsillitis, pneumonia). Diverse other infections: genitourinary tract disorders including syphilis; ear and eye infections. Gastrointestinal tract: nausea, stomach-ache, constipation, gastric discomfort. Studies of P. grandis have shown gastroprotective properties due to diterpene components (Rodrigues 2010); also anti-ulcer and antisecretory properties (Schultz 2007). Hepatoprotective in rats with obstructive cholestasis (Battochio 2005). Painful conditions: gastritis, intestinal spasms, abdominal pain, dysuria, muscular pain, backache, bone dislocation, neck stiffness. Investigations have shown intestinal relaxant and antispasmodic activity for the essential oil which was linked to α-pinene (Camara 2003).

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary Nervous system: convulsions, insomnia, psychiatric problems (including ‘madness’, depression), mental retardation. Herbal tea has acetylcholinesterase inhibitory properties; rosmarinic acid crosses the blood–brain barrier (Fale 2012, 2011). Leaf extracts have anticonvulsant properties (Borges Fernandes 2012). Fertility: use as an emmenagogue, oral abortifacient or contraceptive. Animal studies show an anti-implantation effect. Skin: skin rashes, fungal infections (ringworm, candida). ENT: earache Eye: conjunctivitis; herb used as source of anti-glaucoma drugs. Anti-parasitic: traditional use for treating fevers and malaria; antiplasmodial activity against Plasmodium falciparum, possibly due to abietane diterpene components (AlMusayeib 2012; Van Zyl 2008). Diuretic activity for leaf extracts (Patel 2010).

Plectranthus vettiveroides (syn. Coleus vettiveroides) Note: This species and P. rotundifolius may be the same, although this requires clarification

Similar reputation to the above for gastrointestinal and neurological disorders (including ‘insanity’). Genitourinary problems: notably strangury; genitourinary ‘stimulant’ effect; utilised as emmenagogue for menstrual disorders. Eye problems (burning eyes). Skin problems (skin infections, leucoderma) and leprosy. Fevers and ‘intrinsic’ haemorrhage. Other: useful thirst-quenching properties and has been used to promote hair growth.

 Forskolin

Plectranthus barbatus. (Courtesy Tarcisio Kennedy)

Forskolin (a labdane diterpene that was originally named coleonol in 1974) was a particularly important chemical discovery from Plectranthus barbatus (syn. Coleus forskohlii). Applied to the eye it is an effective antiglaucoma drug that lowers intra-ocular pressure. Forskolin has been extensively investigated as a hypotensive and cardiotonic agent – which certainly reflects the traditional use of this herb for heart and circulatory problems (angina, muscular pain, hypertension, haemorrhage). Forskolin has been utilised clinically as a vasodilatory, hypotensive, cardiotonic agent. While it appears to have therapeutic potential for stroke (cerebral

vascular insufficiency), monitoring is required with some drug combinations (particularly blood-thinning medication) because it has shown inhibitory effects on platelet aggregation.   Forskolin has practical potential for numerous other conditions due to muscle-relaxant and antispasmodic properties. Clinical studies suggest its use for the treatment of asthma and other forms of respiratory distress. Furthermore, it may be beneficial for digestive disorders such as malabsorption syndromes due to a stimulatory effect on digestive secretions – although care should be exercised in individuals with gastric ulceration (Altern Med Rev 2006). Interestingly, Plectranthus barbatus has been employed as an anti-ulcer remedy in Brazilian folk medicine – and an antisecretory diterpenoid (plectrinone A) was isolated from herbal extracts (Schultz 2007). Recently, interest has been expressed in the potential of forskolin as a weight-loss agent for treating obesity. Some clinical results have also suggested benefits for bone mass and testosterone levels, albeit unconfirmed. This has, unfortunately, led to opportunistic marketing enterprises touting its use as a body-building supplement (Godard 2005). Obviously forskolin has a pretty impressive therapeutic repertoire. Even so, it appears that there is room for more clinical advances, with

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forskolin showing experimental anticancer activity, antidepressant, and immunostimulating properties. It has potential for use in thyroid problems (increases thyroid hormone production and release), allergic disorders and psoriasis (Altern Med Rev 2006). Some research has focused on the local application of forskolin to induce a suntan and its ability to prevent the skin burning on UV light exposure. It does this by the induction of eumelanin production in the skin and, despite worries about an adverse stimulatory action on melanin cells, animal studies have not shown untoward side-effects. Indeed, recent investigations suggest that forskolin may have a DNA protective effect (Passeron 2009; Spry 2009; Minkel 2006). Moreover, forskolin has shown an ability to enhance the activity of antibiotics used against urinary tract infections7 – although this requires confirmation (Khamsi 2007). Investigations of the ability of forskolin to affect acetylcholinesterase levels have also focused on chemoprotective potential against organophosphate poisoning, including that associated with chemical warfare agents (Curtin 2006).

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have similar antibacterial properties, with the latter also showing anti-yeast activity (Goncalves 2012; Mohamed 2006). Plectranthus barbatus (root and leaf ) and P. neochilus (leaf ) showed strong anti-Candida activity that support the traditional African use of these plants for infective skin disorders (Runyoro 2006; Tempone 2008; Kisangau 2007). The latter is also utilised in the treatment of respiratory infections in South Africa, which suggests the herb has additional antimicrobial value (York 2011). Certainly, this tends to indicate that further evaluation of the Australian genus is warranted.

7 Plectranthus ornatus and P. fruticosus also contain diterpenes, some of which have antimicrobial properties. The latter has been used as a burn-healing remedy in Poland (Lukhoba 2006).

Antifungal Plectranthus

The essential oils of various species of Plectranthus have shown good antimicrobial potential, with some plant extracts demonstrating strong antifungal activity. Studies of Plectranthus cylindraceus, a herb used as a topical disinfectant in Oman, confirmed a broadspectrum antimicrobial activity for the essential oil. It was active against bacteria (Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis), yeast (Candida albicans) and a wide range of fungi (Alternaria alternata, Bipolaris sp., Curvularia lunata, Fusarium oxysporum and Stemphylium solani) – including dermatophytes responsible for skin infections (Microsporum canis, M. gypseum, Trichophyton rubrum) (Marwah 2007). Plectranthus amboinicus and P. coleoides essential oils

The Blue Coleus or Lobster Flower (Plectranthus neochilus) is a South African native that can be found around the Sydney region. Like many others in the genus it has fragrant qualities, albeit described as being ‘unpleasantly aromatic’. This is a pollution-tolerant herb with fluorineretentive qualities that is said to be able to help improve air quality (Campos 2010). This species has been utilised in the treatment of hepatic insufficiency and dyspepsia in Brazil, the fresh leaves made into an infusion (Duarte & Lopes 2007). The essential oil has also shown antiparasitic (anti-schistosomal) properties worthy of further investigation (Caixeta 2011). An ointment made from Blue Coleus, which was utilised for promoting healing following sterilisation in cats, also gave good results as a local analgesic application (Ferreira nd).

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Other species with similar interesting antimicrobial properties include Plectranthus elegans, P. incanus, P. grandidentatus and P. heretoensis. The latter two contain diterpenoids active against drug-resistant bacteria (MRSA and VRE) (Marwah 2007; Gaspar-Marques 2006). Plectranthus amboinicus essential oil has broadspectrum fungitoxic properties with potential for use as an antimicrobial to prevent food spoilage (Murthy 2009). In addition, rosmarinic acid was identified as a major component of Plectranthus barbatus and P. ecklonii extracts with antibacterial properties against cariogenic bacteria (Streptococcus sobrinus, S. mutans), making these herbs useful candidates for oral care purposes (Figueiredo 2010). Plectranthus ecklonii possessed additional activity against mycobacteria (M. tuberculosis) and Listeria (L. monocytogenes, a gram-positive bacterium). In particular, parviflorons D and F from herb extracts demonstrated broad-spectrum antibacterial properties that suggest good antiseptic potential. The herb has been used as a remedy for skin infections in Africa (Zimbabwe) – as well as having a reputation for being useful in gastrointestinal distress (stomachache, nausea, vomiting) and meningitis. Extracts contain flavonoids, as well as caffeic acid derivatives (nepetoidins A and B)8 – the latter being of interest due to their antifungal activity, as well as possessing potent free-radical scavenging properties superior to rosmarinic acid and gallic acid (Nyila 2009; Lukhoba 2006; Grayer 2003; Nyanyiwa & Gundidza 1999).

Plectranthus ecklonii, which is naturalised in New South Wales and Victoria, is a medicinal species with antifungal, antibacterial and anti-inflammatory potential. (Courtesy kaiyanwong223, flickr) 8 These compounds have been found in leaf extracts of a number of Plectranthus species (see Lukhoba 2006).

Analysis has shown that the essential oils of the different species can differ markedly in their chemical components: • P  lectranthus barbatus (fresh aerial parts): β-farnesene (24–86%), D-germacrene (21.4%), α-copaene (12.68%), α-zingiberene (4.44%) (Marques 2012). • P  lectranthus barbatus (dried aerial parts): caryophyllene oxide (36.41%), α-copaene (17.12%), α-pinene (10.92%), β-farnesene (6.9%), α-zingiberene (1.17%) (Marques 2012).9 • P  lectranthus barbatus (essential oil): substantial differences occurred in the main component of the oil sourced from different parts of the plant: α-pinene (leaves: 22.2%); β-phellandrene (stems: 26.1%); (Z)-βocimene (roots 37.6%) (Waldia 2011). • P  lectranthus coleoides: thymol (57.57%), y-terpinene (15.37%), p-cymene (9.07%), trans-caryophyllene (5.81%) (Mohamed 2006). • P  lectranthus cylindraceus: carvacrol (46.8%), α-terpinolene (18.2%) (Marwah 2007) • P  lectranthus fruticosus: sabinyl acetate at very high levels (60%) (Fournier 1986). • P  lectranthus grandis9: trans-caryophyllene (31.3– 40.2%), germacrene D (12.5–24.5%), eugenol (15.4%) (de Albuquerque 2006). • P  lectranthus melissoides (oil): carvacrol (41.3%), p-cymene (17.4%), y-terpinene (10.1%) with smaller amounts of methyl thymol (3%), thymol (7.9%) and carvacrol acetate (4.6%) (Waldia 2011).  lectranthus neochilus: β-caryophyllene (28.23%), • P α-thujene (12.22%), α-pinene (12.63%), β-pinene (6.19%), germacrene D (5.36%), and caryophyllene oxide (5.37%) (Caixeta 2011). • P  lectranthus ornatus: trans-caryophyllene (9.6– 62.4%), eugenol (38.0%), thymol (14.1%) (de Albuquerque 2006). Other samples from the dried aerial parts differed somewhat: caryophyllene oxide (10.73%), β-farnesene (18.5%), α-pinene (10.83%), α-thujene (17.6%), β-bourbonene (7.98%). However, volatile oil samples from fresh aerial parts differed considerably: β-farnesene (28.83%), 1-octen-3-ol (11.85%), β-bourbonene (8.07%) (Marques 2012).

9 Marques (2012) showed that the fresh volatile oil from samples of P. barbatus and P. grandis were very similar. P. grandis (fresh aerial parts) contained β-farnesene (16.22%), D-germacrene (21.4%), α-copaene (12.38%). Dried samples differed: caryophyllene oxide (35.03%), α-copaene (17.85%), α-pinene (8.56%), β-farnesene (4.31%). β-caryophyllene, which begins to oxidise immediately upon air exposure, has shown only a weak sensitising capacity. However caryophyllene oxide, which was found at higher levels in dried material, has been identified as an allergen of moderate strength (Marques 2012).

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Sneezeweeds  C  entipeda: A Widespread Australian Genus

Plectranthus coleoides has been utilised medicinally in India – the leaf juice was taken by pregnant women to moderate the pain of delivery. The leaf paste was applied to wounds to promote healing, or the leaf juice boiled with coconut oil and used as a lotion to stimulate hair growth (Ignacimuthu 2006). (Image courtesy Jerzy Opiola, Wikimedia Commons)

Toxicological reservations have been expressed regarding the oil of Plectranthus fruticosus (pictured above). Abortifacient properties and foetal toxicity were shown in animal studies and sabinyl acetate was identified as the abortifacient agent – although it was not foetotoxic. This compound is also present in Spanish Sage oil (Salvia lavandulifolia), although there can be large variations (0.1–24%) dependent upon the subspecies (highest levels were found in subsp. velera), chemotype and plant origin. It is also a component of Savin oil (Juniperus sabina) which has abortifacient properties (Fournier 1992, 1992, 1986; Chamorro 1991). Low levels may be present in Celery seed oil, Bergamot oil and Oregano oil (Oreganum vulgare subsp. vulgare) (www. thegoodscentscompany.com). (Image courtesy Kim & Forest Starr, Hawaii)

Old Man Weed (Centipeda cunninghamii). (Courtesy Michael O’Dwyer, Friends of the Earth, Melbourne)

The aromatic herb, Spreading Sneezeweed (Centipeda minima, formerly C. orbicularis or Myriogyne minuta), earned its common name due to a potent sternutatory effect. It provided an excellent snuff that was exceptionally effective at inducing sneezing – a property deemed useful for relieving congestion of the head during colds or influenza. This small plant is widespread throughout the Indo-Pacific region and has been used in a remarkably similar manner wherever it grows – in countries ranging from China and Japan, to India, Malaysia, the Philippines and Australia. Indeed, the herb’s natural range extends as far as Madagascar. In Australia two other closely related species were used interchangeably as ‘Sneezeweeds’ – the Common Sneezeweed (Centipeda cunninghamii), and the Desert Sneezeweed (C. thespidioides). Overall there are eight native species, all of which are widely distributed across the continent: • Centipeda cunninghamii, which is the most widespread, is found throughout the continent, extending to Tasmania; • Centipeda borealis and C. minima subsp. macrocephala: Western Australia, Northern Territory, Queensland; • Centipeda minima subsp minima has a wider distribution from the northern tropics to South Australia, New South Wales and Victoria;

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• Centipeda crateriformis, C. nidiformis, C. pleiocephala and C. thespidioides share a similar distribution (WA, NT, Qld, NSW, Vic., SA); • Centipeda racemosa (WA, NT, Qld, NSW), however, does not extend to the southern states. Australian Aboriginal people crushed Sneezeweed and inhaled the vapour to ease head congestion or headache. Alternatively, it could be bound around the head to inhale the aroma, although the latter practice had one substantial pitfall. All these herbs are extremely aromatic with a fragrance that is usually regard as being quite ‘objectionable’.10 More unusual was its deployment as a substitute for the narcotic plant Pituri (Duboisia hopwoodii) or the native ‘Wild Tobacco’ (Nicotiana spp.) when these were unavailable (Latz 1996). Joseph Maiden (1888b) mentioned that in Indian herbal traditions the remedy was not only valued for its decongestant abilities, adding: ‘The natives of India consider it a hot and dry medicine, useful in paralysis, pains in the joints and special diseases; it is also used as vermifuge [Cyclopedia of India]’. The seed and herb have been employed for the treatment of toothache, hemicrania (headache), and worm infestations (Satyavati 1976). In the late 1800s Sneezeweed was a popular remedy for treating the eye infection known as ‘sandy blight’. Joseph Maiden (1888a) noted: ‘if this plant only partially realised the expectations formed of it, it will be a valuable addition to our indigenous vegetable materia medica’. The words of Thomas Mitchell, on his expedition from Sydney to the Gulf of Carpentaria, provide an insight into the seriousness of this condition: ‘This morning I awoke completely blind, from ophthalmia, and was obliged to have poultices laid on my eyes; several of the men were also affected in the same manner. The exciting cause of this malady in an organ presenting a moist surface [the eye] was, obviously, the warm air totally devoid of moisture, and likely to produce the same effect until the weather changed’ (24 January 1846). However, his treatment the next day was somewhat more invasive, and decidedly less pleasant, than the herbal alternative: ‘Dr Stephenson having recommended the 10 Sneezeweeds have been utilised as ant-deterrents around campsites. The herb has also been a suspected stock poison (Latz 1996).

application of leeches, and having observed them in the ponds at Nyingan, I sent William Baldock and Yuranigh there in search of some, and they brought back enough. Fourteen were applied to my eyes the same afternoon.’ Fortunately, his eyesight improved quite rapidly over the following days. The whole experience was extremely difficult for the surveyorexplorer as the awful thought of failure loomed: ‘to have abandoned the undertaking at that point, would have been almost as painful to me as the other alternative’ (Mitchell 1848).

  The Medicinal Leech

Invoice for ‘57 Choice Leeches’ sold to Swindon businessman Mr John Green, 12 May 1870. This unusual Victorian illustrated invoice was from Fitch & Nottingham, 16 & 17 St Peter Street, Hackney Road, London. (Image courtesy Swindon Collection, Central Library, Berkshire)

There are more than a hundred different native species of leech in Australia. Surprisingly, they are actually a type of segmented worm (Annelids) and therefore closely related to earthworms. Leeches contain an anticoagulant that they use to facilitate blood flow from their host – and this has extremely useful medicinal properties. Indeed, leeches continue to be utilised today for some forms of surgery, notably microsurgical procedures involving tissue damage that requires the removal of clotted blood.   An interesting Belgian study on leech feeding behaviour examined some old methods of motivating uncooperative leeches – which can, at times, be unenthusiastic about the job.

VALIDATING BUSH MEDICINES

Despite rumours to the contrary, the use of sour cream did not appear to change matters much, and garlic was simply lethal – a fatally attractive arrangement. However, nineteenth-century physicians also dipped leeches in beer before use. Unfortunately, this strategy did not appear to help matters much either: ‘After exposure to beer leeches changed behaviour, swaying their forebodies, losing grip, or falling on their backs’. It appears that the leeches became quite inebriated when they sampled Guinness Stout and Hansa Bock (Baerheim & Sandvik 1994).

Leeches for sale in the Egyptian Bazaar, Istanbul. (Courtesy Marcus Beard, flickr)

It was no wonder that interest was quickly aroused in any remedy with such singular efficacy. Maiden’s writings help to trace some of Sneezeweed’s medicinal history: I find from a communication of Baron Mueller, that for some time past he has had an idea that Myriogyne [Centipeda] might be utilised for medicinal purposes, and that he had actually submitted it to Dr. Springthorp, an eminent physician in Melbourne, for the purpose of experiment. The Baron, however was not aware of its efficacy in simple ophthalmic inflammation, and he regarded the discovery as interesting. I mention this as a matter of justice to Dr. Jockel who, I believe, is the first medical man in Australia who has proved the value of Myriogyne in the case of ophthalmia. This weed, growing as it does on the banks of rivers and creeks, and in moist places, is common to all the Australian colonies and Tasmania, and it may be regarded as almost co-extensive with the disease it is designed to relieve. It is described in the Flora Australiensis … and figured amongst Baron Mueller’s plants of Victoria. In the document relating to

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the Intercolonial Exhibition, 1866–1867, it is noticed as remarkable for its sternutatory properties, and recommended for the manufacture of snuff (Maiden 1898).

The willingness of some enterprising medical practitioners of the time to investigate native plant remedies was heartening. They quickly embraced the practical usefulness of many herbs – without the derision that later haunted the use of medicinal plants following the development of synthetic drugs. The Reverend Dr Woolls gave an interesting account of the rather serendipitous investigation of Sneezeweed. In a letter to the editor of the Sydney Morning Herald, Christmas Day 1886, he reported: Some weeks since, the Rev S. G. Fielding of Wellington, called my attention to a weed (known to botanists as Myriogne minuta, of the Compositae order) which he stated had been used with success in cases of blight. Being anxious to test the efficacy of the remedy, and to ascertain whether any bad effects would arise from its application, I placed some of it in the hands of Dr. Jockel of this town who has furnished me with the following remarks: ‘I have much pleasure in testifying to the efficacy, in cases of ophthalmia, of the plant which you so kindly sent me. A case came under my notice a few days ago of a drover who was suffering from a severe form of purulent ophthalmia, contracted up country. I made an infusion of the plant according to directions, and the first local application seemed to have almost a magical effect. The man expressed himself relieved at once of the intense smarting which he had previously suffered. He got on so well that in 2 days he was able to start back up country again, and could hardly express his gratitude for the very great relief afforded. Louis C. Jockel’ (Maiden 1888b).

The remedy rapidly entered into popular use. Maiden later commented: ‘this use of the plant as a cure for sandy blight is fairly well known in the Colony; how long it has been known I cannot say. It was packed in tins by one enterprising firm and sold as “Magic Ophthalmia cure” with what business results I do not know. It can be said of this remedy that if its effects are not beneficial in any particular case, they can scarcely be injurious’ (Maiden 1898). Although the herb had obvious successes in many cases of ‘ophthalmia’, there would have been some limitations on its efficacy. Because eye inflammation can be due to a variety of pathogens, doubtless some of them would have been resistant to the remedy. Additionally, the quality of the preparation would have had an

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important influence – and some caution was in order regarding its application. The Revered Woolls (1887) warned: ‘Myriogyne minuta in decoction has been found useful in cases of ophthalmia or blight, but careful observation is required to ascertain the proper proportion in which it should be used, and also the best method of application. If the decoction is too strong it occasions much pain and therefore care is necessary in the preparation of it.’ Over the last century Sneezeweed, which was known colloquially as the ‘Old Man Weed’, has continued to be used by Aboriginal people. In 1974 an article by Alistair Campbell on the ‘pharmacy’ of the Victorian Aborigines deemed Centipeda cunninghamii worthy of further examination: ‘It was used in medicine by Aborigines of Lake Hindemarsh in 1873. It was still in use in 1970 at Cummeragunga where a decoction was made by boiling the plant in water and straining. A sample of the decoction was obtained, it was black in colour. It was taken as a cure for ill-health including tuberculosis and as a lotion for skin infections. Its active principle, if any, is unknown and does not appear to have been investigated.’ The extended use of the herb (for around two years) was even said to help resolve a case of tuberculosis. The lotion has also been valued for treating diverse skin disorders such as rashes, ulceration and acne. CSIRO (Commonwealth Scientific and Industrial Research Organisation) investigations in Australia determined that the herb had a slight anti-pyretic and anti-diuretic activity (Collins 1990).

Cosmetics from Centipeda Overall, more than 60 components have been identified in Centipeda cunninghamii essential oil, extracted from the leaves and flowering tops of the shrub – albeit most were present only in very small amounts. The oil was found to be primarily composed of cis-chrysanthenyl acetate (sample 1: 30.57%; sample 2: 13.54%) or cischrysanthenol (sample 2: 23.89%; sample 1: 9.7%) and myrtenyl acetate (22.97–23.94%). Smaller amounts of thymol (4.64–6.08%), myrtenol (5.85–8.2%) and myrtenal (0.17– 2.78%) were also present (www.phyoxolin.com. au; see Beattie 2009 for a full chemical review).

A diverse range of compounds can also be found in plant extracts. They include flavonoids from the flowers, caffeic acids from the stems (e.g. chlorogenic acid), a thymol derivative and a sesquiterpene lactone (arnicolide). Extracts possess potent anti-inflammatory and antioxidant properties, with some components exhibiting activity comparable to the green tea antioxidant epicatechin (Beattie 2009; Gabriel 2005). Extracts have also shown antibacterial and antifungal properties (Palombo & Semple 2001; Hill 1997). Centipeda has thus been suggested to have particular application as a skin-healing, rehydrating and cellular protective agent. The patented herbal products Phyoxolin and Plantolin have been marketed as anti-ageing, anti-wrinkle, soothing, restorative products useful for irritated and cracked skin disorders (dermatitis), herpes infections, psoriasis, eczema, acne, rosacea, sunburn and general purpose skin cosmetic use (Beattie 2009; Gupta & Hoyt 2006; www.phyoxolin.com.au; www.plantolin. com). Other suggests include the use of the herb for oral disorders such as periodontal infections and gingivitis (D’Amelio & Mirhom 2005). Centipeda cunninghamii-based products have also been proposed for use for baby skin disorders such as nappy rash – as well as shaving creams, toothpaste formulations, hair care, bath products and shower gels. It appears to be suitable for a wide range of other cosmetics, skin lotions and creams – including antibacterial face washes, makeup removers and hydrating face masks (European Patent EP0988044).

Centipeda in Chinese Medicine The varied use of Centipeda minima in Chinese medicine traditions is illustrative of the extensive therapeutic potential of this herb. The plant was collected and dried when in full flower, or when the flowers were beginning to open, and simply utilised as an infusion. Similar to the use of Sneezeweed in Australia, it was regarded as having antitussive, expectorant, anti-allergic, anti-asthmatic, diaphoretic and anodyne (pain-killing) properties – being primarily recommended as a respiratory tonic and

VALIDATING BUSH MEDICINES

to improve eyesight. Not only was it useful for treating the common cold and rhinitis, it was taken to ease coughing (including whooping cough), relieve rheumatic pain, alleviate dysentery and treat snakebite. The herb has a broad spectrum of antibacterial activity High grade granulated (against Pseudomonas Centipeda herb for use in sp., Proteus sp., Bacillus herbal dispensary. (Image courtesy Acuneeds Pty Ltd, typhi, B. dysenteriae and Staphylococcus aureus) Sydney) (Yeung 1985). It was also utilised for treating ‘internal injuries’ – although a more unusual recommendation was the use of the herbal decoction (taken alone or with wine) to counteract opium poisoning (Perry & Metzger 1980). In Nepal, the popular use of Sneezeweed juice (inhaled or taken internally) for coughs and colds inspired investigations of its antiviral potential. Extracts demonstrated activity against the Sindbis, Herpes simplex and polio viruses. Antibacterial activity was confirmed against Bacillus subtilis and Staphylococcus aureus, with this activity being attributed to the presence of sesquiterpene lactones (Liang 2007a; Taylor & Towers 1998; Taylor 1996). Antibacterial thymol derivatives are also present (Liang 2007b). Moreover, the plant contains flavonoids that were linked to a potent anti-allergic effect, which helps to substantiate its use for treating asthma and nasal allergies (rhinitis, sinusitis). Extracts have also shown significant anti-inflammatory activity against pleural effusion in animal studies (Liu 2005; Qin 2005; Iwakami 1992). Diverse product patents have been based on these traditional uses of Centipeda minima and subsequent studies – not only for the treatment of allergic disorders and herpes, but also to heal bone fractures, to encourage hair growth, and as an anticancer agent. Its potential as a cosmetic include claims for the relief of itching skin problems and as an anti-ageing cream (Beattie 2009). Preliminary investigations have suggested that the cellular protective effects of Centipeda minima may extend to the prevention of renal tissue damage (Sohn

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2009). There are also a number of studies into the anticancer (anti-tumour, antimutagenic, antiproliferative) potential of the herb and various components, including sesquiterpene lactones and a stilbene. In particular, 6-O-angeloylenolin demonstrated activity against a range of cancer cell lines – while the essential oil had interesting anti-tumour potential against nasopharyngeal cancer cells (Su 2010, 2009; Ding 2009; Changlong 2008; Chabert 2006; Oh 2006; Lee & Lin 1988). Centipeda minima has an interesting history of clinical use for the treatment of a number of infectious and parasitic disorders, including malaria and amoebiasis. The herb has shown moderate experimental activity against Giardia intestinalis – investigations isolated brevilin A (a sesquiterpene lactone) as the anti-giardial component. Additionally, this compound had activity against Entamoeba histolytica (a causative agent of amoebiasis) and the malarial parasite, Plasmodium falciparum (Yu 1994). Other components of pharmacological value in the herb include thymol derivatives, sesquiterpenes and sterols (Liang 2007a, 2007b; Wu 1991, 1985). The latter two classes of chemicals featured in Centipeda extracts with molluscicidal activity against a small tropical freshwater snail (Oncomelania hupensis), which acts as a host for the Schistosoma parasite (Zhao 2010; Ni 2009).

Centipeda contains chemicals active against the tropical freshwater snail Oncomelania hupensis. (Courtesy Qin Ping Zhao. Department of Parasitology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, China)

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Headache Vines

Clematis glycinoides. (Courtesy John Tann, flickr)

Clematis microphylla. (Courtesy Melburnian)

The genus Clematis (Ranunculaceae) is of interest as some species have an irritant reputation similar to the Sneezeweeds. A popular, although somewhat discomfiting, herbal remedy utilised the crushed aromatic leaves of the Headache Vine (Clematis glycinoides), a viney plant of the rainforest margins. The crumbled leaf releases an ammonia-like vapour, which can be inhaled to relieve headaches, although the results are somewhat dramatic. Apparently the fumes provoked such an incredibly painful reaction that the initial headache was quickly forgotten – substituted, instead, by an equally uncomfortable sensation of the head ‘exploding’, the eyes ‘watering’ and intense irritation of the nasal passages. Fortunately, the whole ordeal had a reputation for being effective, although it was probably often only used in an act of sheer desperation when nothing else would work. Even so, some authors have mentioned that there were times when the remedy was totally ineffective. This would appear to be due to the variability of the active constituents. Selwyn Everist (1981) commented: ‘I

have experienced personally both these irritant and analgesic effects but have found that only young leaves or mature leaves in vigorous sappy growth are effective. Prolonged rubbing of the crushed leaf can blister the palms of the hands.’ The latter is not so surprising as Clematis belongs to the Ranunculaceae (Buttercup family) – which is known for its acid and irritant properties.   There are four species of Clematis in Australia, three of which are native – C. glycinoides, C. aristata and C. microphylla. Traveller’s Joy (Clematis vitalba) is an introduced garden ornamental in some regions. All are wiry climbing vines, producing sweetly-scented masses of white starry flowers – which can make them quite difficult to tell apart. The Small Clematis (C. microphylla) has a wider distribution than the Headache Vine (C. glycinoides, a rainforest species) and extends into southern temperate climates, preferring a drier habitat. Clematis aristata has a similar temperate distribution. The irritant properties of the Headache Vine were shared by the Small Clematis (Clematis microphylla). In 1931, JB Cleland recorded a few details regarding its practical use in the Medical Journal of Australia. A leaf poultice was employed as a counter-irritant: In the case of my informant, a middle-aged lady, the poultice had been applied for too long a time to a knee which was affected with chronic rheumatism. To make the poultice, the leaves were stripped from the stems and cut up. Enough boiling water was poured on to make the mass sodden, and the leaves were crushed to express the juice. A fairly thick poultice was made of the leaves and the juice and applied to the affected part. This was left on for seven minutes, whereas it should have been applied for not more than three. On removal, nothing was apparent except redness. Twelve hours later blisters were forming,

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Clematis vitalba. (Courtesy Michael Gasperl, Wikimedia Commons, CC-by-SA 3.0 Unported)

The juice of the Traveller’s Joy (Clematis vitalba), introduced into the nostrils, was once a common migraine and headache remedy – despite highly irritant side-effects that could damage the mucous membranes (Chiej 1988). It is interesting that indigenous medicine in Papua New Guinea employed a local species similarly. At Finschhafen the leaves of Clematis papuasica were crushed and inhaled to clear blocked nasal passages – as well as being used to treat colds in other regions of the country (Woodley 1991).

which were ruptured. The patient had to keep in bed for a week and the knee was painful for another ten days, but the rheumatism was much benefited.

It sounds like another method of pain relief that would only be used as a last resort. The irritant effects are present throughout the genus – with many species having a similar reputation across the world, including the European Traveller’s Joy (Clematis vitalba) and C. cirrhosa (Chiej 1988). Maude Grieve (1931) provided a rather graphic description of the use of the Upright Virgin’s Bower (Clematis recta) as a decongestant for sinus problems: ‘The leaves and flowers when bruised irritate the eyes and throat giving rise to a flow of tears and coughing; applied to the skin they produce inflammation and vesication, hence the name Flammula Jovis’. Various African herbs (e.g. Clematis brachiata, C. hirsuta and C. oweniae) were likewise used to induce sneezing to clear head colds or headaches. The Ronga even

Clematis, along with Mimulus and Impatiens, were the first three remedies that formed the basis of the Bach Flower Remedies. Clematis is one of the five basic components of Rescue Remedy. The feathery Clematis seeds appear to be ‘longing to be blown away and start again’ – so this remedy has an association with a scatterbrained, dreamy type of personality, or the ‘absent-minded professor’, a characteristic so often linked with great creative potential. (Image courtesy Tanakawho, Tokyo, Japan, Wikimedia Commons, CC-by-SA 2.0)

‘steamed’ patients suffering malaria and colds with Clematis oweniae boiled in hot water, as well as taking it as a tea. In Tanganyika Clematis hirsuta was often placed on heated stones ‘to facilitate volatilization’ (Watt & Breyer-Brandjwijk 1962). Fortunately, the acrid, burning taste characteristic of these plants was said to be ‘greatly diminished’ during storage – which seems to indicate the loss of an irritant essential oil component – and processing

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The Erect Clematis or Upright Virgin’s Bower (Clematis recta), like many of the genus, appears to have antimicrobial properties. It has been utilised for treating syphilis, cancerous sores, diverse other forms of ‘foul ulcers’, and as a diuretic or diaphoretic agent (Grieve 1931). (Image courtesy Nuuuuuuuuuuull, flickr)

Clematis recta (as Clematis erecta) from Edward Hamilton, Flora Homoeopathica, Illustrations and descriptions of the Medicinal Plants used as Homoeopathic Remedies, Leath & Ross, St Paul’s Churchyard, Oxford St, London, 1852.

methods such as drying or decocting could reduce their unpleasant effects. In 1830 the botanist CS Rafinesque recorded the following comments regarding American species of Clematis11: ‘Almost all species medicinal … The bark and blossoms acrid, raising blisters on the skin; a corrosive poison internally, loses the virulence by concoction [cooking] and desiccation’.

11 In American traditions the Virgin’s Bower (C. virgiana) leaf and flower infusion was used to relieve severe headaches (Lust 1974). ‘Pepper Vine’ (C. ligusticifolia) leaves (fresh leaf juice or dried herb) provided a decongestant snuff (Moerman 1986).

The genus Thalictrum (Ranunculaceae) has a very similar reputation to the Clematis herbs. In Indian medicine Thalictrum foliolosum12 yielded a snuff useful for clearing ‘the brain’ and for coryza (a congestive head cold), or applied locally as a toothache remedy. Traditionally, the root has been valued for chronic dyspepsia and other digestive problems (e.g. flatulence), visceral obstructions, jaundice, ophthalmia – and as a convalescent remedy following an acute illness (Kapoor 1990). (Image courtesy C Basset, asianflora.com) 12 This species contains the antimicrobial agent berberine, as well as isoquinoline alkaloids (thalictrine, palmatine, jetrorrhizine) (Kapoor 1990).

VALIDATING BUSH MEDICINES

Clematis as Antibacterials and Diuretics

Western Clematis (Clematis ligusticifolia). (Upper image courtesy Chris Savastio, Jr.; lower image courtesy Arlene K. Schag, flickr)

The use of the Clematis genus as wound-healing This description is reminiscent both the antibacterial agents appears to be wellofknown to European and Chinese deployment the genus. many cultures. Constantine Samuel of Rafinesque In America the spicy of (among ‘Pepper other Vine’ (1830), an academic andleaves botanist (Clematis ligusticifolia) also of in Clematis demand. things), mentioned that were a number Thisanalgesic herb had analgesic reputation that led had andanantibacterial healing properties wider on usethe forflora pain relief: lotions were intohisitswritings of Northern America: applied to backaches, swollen legs or13arms, ‘The extract used for osteocopic pain , dose while 1 or were useful for oily easing rheumatic 2poultices grains; frictions of an liniment curepains. the Furthermore, leaf washand wasCl. utilised as aare healing itch. Our Cl. avirginica viorna also agentas for soresand orsudorific, boils forforboth man (e.g. used diuretic chronic syphilitic animals (Moerman 1986). … Bruisedsores) greenand leaves used by our empirics as Remarkably recommendations have been escharotic foerealsimilar ulcers, and detergent for other made for other species across the globe. In Africa sores.’ Clematis brachiata was used in the treatment of sexually transmitted diseases (including gonorrhoea and syphilis), while C. oweniae (root cooked with  

13 A violent form of bone pain that is fixed at a specific location.

This description is reminiscent of both the European and Chinese deployment of the genus. In America the spicy leaves of ‘Pepper Vine’ (Clematis ligusticifolia) were also in demand. This herb had an analgesic reputation that led to its wider use for pain relief: lotions were applied to backaches, swollen legs or arms, while poultices were useful for easing rheumatic pains. Furthermore, a leaf wash was utilised as a healing agent for sores or boils for both man (e.g. syphilitic sores) and animals (Moerman 1986). Remarkably similar recommendations have been made for other species across the globe. In Africa Clematis brachiata was used in the treatment of sexually transmitted diseases (including gonorrhoea and syphilis), while C. oweniae (root cooked with salt and nut oil from Trichilia roka) provided a remedy for thrush and coughs. Clematis hirsuta or C. sinensis poultices were also applied locally to ‘draw’ septic lesions (Watt & Breyer-Brandwijk 1962). Clematis hirsuta has shown ‘pronounced antifungal activity’ against Candida albicans and a number of common skin fungi (Cos 2002). An interesting Central American study of the anti-gonorrhoeal potential of Guatemalan plants noted that Clematis dioica was effective against various strains of the gonorrhoea bacterium (Neisseria gonorrhoeae) (Caceres 1995). The efficacy of some species in urinary tract disorders may well have influenced their use in venereal disease. Clematis recta was used as a diuretic and diaphoretic in Europe (Grieve 1931), while the Himalayan C. montana was recommended for urination problems (pain and excessive discharge) in China – as well as having a sedative effect useful for insomnia or restlessness (Chin & Keng 1990). Diverse other species have antimicrobial potential. In Cypriot traditions Clematis cirrhosa provided a leprosy remedy, the leaves (crushed or powdered) applied externally – as well as being useful for irritant skin diseases such as psoriasis and dermatitis (Georgiades 1987). The leaves of Clematis papuasica in Papua New Guinea were utilised for treating skin infections and appear to have effective antifungal activity – with studies showing a wide spectrum of antimicrobial properties for leaf and stem-bark extracts (Khan 2001, Woodley 1991).

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An Aromatic Irritant: Tickweed (Cleome viscosa)

Clematis flammula has been used for dropsy (to reduce oedema) in Turkey (Yesilada 1997). (Image courtesy Jean-François Gaffard, CC-by-SA)

Chinese Clematis Root (primarily sourced from Clematis chinensis14) provides an illustration of the varied scope of these plants in traditional medicine. The herb has an excellent reputation as an antirheumatic and analgesic – as well as possessing substantial anti-inflammatory properties for treating conditions as diverse as hepatitis, tonsillitis, laryngitis, skin and breast inflammation, and the parasitic disease filariasis. Investigations have supported the therapeutic effects of the remedy: hypotensive, anti-diuretic, anti-inflammatory, antispasmodic, sedative, antibacterial, anti-malarial, antitumour and hypoglycaemic (blood sugar-lowering) properties. Combined with vinegar and brown sugar it also had an unusual reputation for softening fish bones lodged in the throat. One study of 104 cases of fish bone impaction that were treated with this herb recorded an 85 per cent success rate (Li 2003; Wei 1991; Chiu 1988; Yeung 1985; Bensky & Gamble 1986).

14 Other resources include C. hexapetala, C. armandi, C. uncinata, C. meyeniana, C. henryi, C. finetiana, C. manshurica and C. paniculata (Yen 1992).

The genus Cleome (Cleomaceae family)15 is well represented in Australia – with around 20 species that are primarily found in the Northern Territory and Western Australia. They are commonly known as ‘spiderflowers’ due to their spider-like blossoms. Of these, the Yellow Spiderflower or Tickweed, Cleome viscosa, is a well-known medicinal herb that is found throughout the world’s tropics. It has a wide distribution throughout most of mainland Australia – although it does not extend to New South Wales and Victoria. (Upper image courtesy Smithsonian Institution, Plant Image Collection, United States Virgin Islands, Saint John, Cruz Bay Quarter; lower image courtesy Jeevan Jose) 15 While Cleome is usually placed in the Cleomaceae (along with the genera Cleomella, Gyandropsis and Physostemon), it was formerly classified in the Caper family (Capparaceae).

VALIDATING BUSH MEDICINES

Cleome viscosa is a highly aromatic weedy herb. Although it is not botanically related to Clematis, it has a very similar reputation. Aboriginal people used the mashed plant as a poultice for rheumatism, swellings, ulcers, open sores, headaches and for treating colds (Isaacs 1994; Barr 1993, 1988; Webb 1969).   It has an equally extensive medicinal reputation in Indian traditions, where the leaves were utilised to relieve headache, joint pain and innumerable types of skin infection. An ointment (leaves boiled in ghee) has been considered useful for wounds, or the leaf simply applied directly to ulcers, snake bites and scorpion stings. The warmed leaf juice provided a readily available remedy for earache or deafness, and could be used as an eye wash. The seeds have been widely utilised for skin diseases, as well as for fevers, diarrhoea, convulsions, and as a vermifuge.16 The seed powder was also taken internally as a remedy for haemorrhoids. The anthelmintic properties of the root and seeds were widely utilised in countries as diverse as Southeast Asia, India, China, Taiwan, Guam, the Philippines, the United States and Africa for intestinal worm infestations. The roots and seeds also provided a cardiac stimulant in Sri Lanka – while in Israel the plant was employed as an antidiabetic remedy (Mali 2010; Katewa & Galav 2005; Lassak & McCarthy 1992; Quisumbing 1951). In many places the aromatic leaves have simply been rubbed in the hands and used as a form of ‘smelling salts’ for sinus congestion or headaches. Cleome droserifolia and C. gynandra have a very similar reputation. Tickweed leaf poultices (mashed with salt) were also widely applied to ease pain such as an aching back or for headache. In the Philippines the herb also provided a useful wash for maggot-infested wounds (Burkill 1985; Perry & Metzger 1980; Satyavati 1976; Quisumbing 1951). In Southeast Asia, Tickweed has been used as a counter-irritant (for a local stimulant effect) – providing a deliberate blistering agent similar to that of a mustard poultice. Bailey (1880) noted: ‘it is used by the natives to relieve headache. It is used in Cochin China as a counter-irritant in the same way as sinapin [extract of black mustard seeds] is in Europe, and also as a vesicant. In the United States the roots 16 Cleome gynandra had a similar reputation. In India a cupful of root extract, mixed in coconut milk with honey (1–2 teaspoons), has been given to children below twelve years age twice a day for 5–6 days to expel intestinal worms (Salave 2011).

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are said to be used as a vermifuge’. Similar uses have been recorded from India and the Philippines. Dr Kirtikar, in Notes on Some Indian Drugs, referred to an exhibit of the seed oil at the Intercolonial Congress of 1882, held in Melbourne: ‘The plant has a great reputation as a remedy for chronic ororrhoea [ear infection]. Its action is chiefly antiseptic, as it contains a powerful volatile principle not unlike in smell to that of the mustard. This active principle has besides stimulating properties. The plant is highly viscous in every part, and is covered over with hairs, which are capped with a sticky gland and smell powerfully.’ The plant (herb, fresh leaves or the seeds) also had a reputation as a mustard substitute. This stimulating effect was due to pungent mustard oil components, which also have antibacterial properties17 (Oliver-Bever 1986). They possibly include sinapine, which is the compound that gives mustard its ‘biting’ flavour. However, as these are volatile components, the plant loses its vesicant and acrid properties upon dessication or heat exposure (Burkill 1985; Satyavati 1976). Investigations have confirmed that Cleome viscosa extracts have a wide range of pharmacological properties: analgesic (whole plant, seeds); anthelmintic and hepatoprotective (seeds); antidiarrhoeal, antipyretic (plant; comparable to paracetamol), and anti-inflammatory (whole plant); immunemodulatory (aerial parts); gastroprotective and anti-Helicobacter (leaves). Extracts have also shown antioxidant and anticancer potential (Mishra 2011; Mali 2010). Furthermore, the plant has potent broadspectrum antimicrobial (antibacterial, antifungal, mycotoxic) activity, as well as wound-healing properties that would support its use in wound and ulcer healing, including treatments for leprosy (Bose 2011; Koppula 2011; Panduraju 2011; Wake 2011; Mali 2010; Silue 2009; Parimaladevi 2003).

17 Mustard oil glucosides (glucosinolates) are important biological components of the Brassicaceae family. Spider plants (herb) contain glucosinolates (e.g. methylglucosinolate, cleomin, glucocapparin) that yield isothiocyanates with strong antimicrobial properties (Silue 2009; Mari 1993; Drobnica 1976). Glucosinolates have also attracted a lot of research interest as dietary anticancer compounds from vegetables such as broccoli and cabbage. This may be linked to the use of the Spiderflower plant as an antitumour application to skin growths.

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The use of Tickweed leaf smoke as a mosquito repellent inspired investigations that found extracts had good larvicidal activity against the malaria mosquito vector Anopheles stephensi – larva is pictured here (Saxena 2000). Seed extracts of Cleome viscosa have traditionally been utilised as an anthelmintic and febrifuge, while the leaves (juice) were specifically recommended for malaria (Mali 2010) – which suggest good antiparasitic potential. In Africa root decoctions of Cleome gynandra have been similarly utilised for treating feverish conditions, including malaria (Fowler 2006) – a use that has been substantiated by studies showing the plant has antimalarial activity against Plasmodium falciparum (Gessler 1994). (Image courtesy CDC USA)

The reputation of these plants as a tick repellent appears to be well justified. Cleome gynandra leaves have repellent and acaricidal effects that were most pronounced on nymphs, with less activity on adult ticks. Even so, observations in the field indicated that the area 2–5 metres around stands of these plants were tick free – which suggested its use in tick-management schemes for farming purposes (Malonza 1992). Evaluation of the essential oil has identified a number of components with effective anti-tick properties (Anbazhagi 2009). Cleome gynandra extracts have also shown activity against red spider mite, diamondback moths, aphids and thrips – which suggest additional active pest-deterrent uses intercropped with vegetables such as tomatoes and cabbages, or for the cut flower trade, particularly roses. Glucosinolates in the leaves (which impart a bitter taste) may contribute to its insecticidal properties (Silue 2009; Nyalala & Grout 2007). There are various uses of Cleome viscosa that suggest an influence on hormonal function. In Papua New Guinea the leaf has been taken as a fertilityenhancing agent (sometimes chewed with betel nut) – with a similar use being recorded for Cleome gynandra in Nigeria and Uganda. Indeed, in Africa this species

Cleome hassleriana. This species has strong antifungal activity against soil-borne pathogens due to its glucosinolate components (glucocapparin, glucocleomin). Importantly, the overall microbial balance of the soil was not adversely affected. This has even led to the suggestion for its use as a green manure that could replace the pesticidal toxin methyl bromide (Lazzeri & Manici 2001; Lazzeri 1998). (Image courtesy Schoinard, Wikimedia Commons, CC-by-SA 3.0 Unported)

is widely recommended as a tonic vegetable during pregnancy which would help facilitate labour and postpartum recovery (Mishra 2011; WHO 2009; Okoli 2007). In Uganda the root decoction was traditionally utilised for the prevention of miscarriage or to hasten childbirth (induce uterine contractions), help remove the afterbirth (including complications with a retained placenta), and to control bleeding following the birth. Studies have shown that root extracts had a weak uterine stimulant effect that could promote the effects of oxytocin during childbirth. Extracts (roots, leaves and flowers) have also been taken to enhance male potency (sexual impotence, erectile dysfunction) (Kamatenesi-Mugisha 2005; Kamatenesi-Mugisha & Oryem-Origa 2005). However, there is evidence that the use of Cleome viscosa can actually reduce the sperm count (Oladele & Abatan 2010).

VALIDATING BUSH MEDICINES

The hepatoprotective properties of seed and leaf extracts of Tickweed are significant, which support its traditional use in the treatment of jaundice. Its effects were found comparable to the premier liver remedy Milk Thistle (Silybum marianum) – and, similar to this herb, Tickweed seed extracts were rich in flavonoids (Mobiya 2010; Gupta & Dixit 2009). Coumarinolignoids (cleomiscosins) from the seeds were identified as highly active hepatoprotective, antiinflammatory and immunomodulatory components (Yadav 2010; Bawankule 2008). A couple of related species with liver-protective potential are Cleome droserifolia and, possibly, C. gynandra, which has been utilised for treating bilious disorders (AbdelKader 2009; Anbazhagi 2009). In addition, Cleome droserifolia has a particularly good reputation as an antidiabetic agent, with potential anti-obesity and cholesterol lowering attributes – although further toxicological evaluation has been recommended (ElKhawaga 2010; Emam 2010; Bnouham 2006).

good reputation as an anti-inflammatory and analgesic agent – as well as being antidotal for scorpion stings. Extracts have shown notable immune-suppressive effects which were linked to an anti-inflammatory activity (Kori 2009). Spiderflower is a useful green vegetable that contains fairly high amounts of β-carotene and vitamin C – as well as moderate amounts of calcium, magnesium and iron. Vegetables often lose vitamin C during the cooking process (losses are usually between 50–90%, sometimes higher) although, in comparison to many other greens, Cleome leaves generally retain good levels (a low level of vitamin C loss: 5–18%) (Seeramulu 1983).

  Cleome gynandra

Cleome gynandra, from Francisco Manuel Blanco, Flora de Filipinas, Gran edicion, Manila, 1880–83.

The Spiderflower Cleome gynandra (syn. Gynandropsis gynandra) is naturalised throughout Queensland, and in a few places in the Northern Territory. (Image courtesy Kim & Forest Starr, Hawaii)

Cleome gynandra is a pretty species with a weedy habit that is often found on waste lands and rubbish dumps. Medicinally, the herb has a

Cleome gynandra seeds. (Courtesy Steve Hurst, UDSA)

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Cleome viscosa seed oil, which is edible, contains a high proportion of polyunsaturated fatty acids (oleic 18.6%; linoleic 32.8%; linolenic 26.6%) in comparison to saturated fatty acids (palmitic 2%; stearic 20%) (Rukmini 1978) – although the analysis provided by a later study suggests the levels of polyunsaturated fatty acids could be somewhat higher (linoleic 70%, oleic 14%), with an associated reduction in the proportion of saturated fatty acids (palmitic 10%; stearic 5%). Volatile components are also present (Mishra 2010). The use of the crushed seed as a folk medicine for treating infantile convulsions and mental disorders suggests that the remedy may affect nervous system function, with investigations showing extracts had anticonvulsant properties (Mishra 2010; Nadkararni & Nadkarani 1992). (Image courtesy Ming-I Weng, Taiwan)

Cleome rutidosperma is naturalised in the Northern Territory and Christmas Island. Extracts of the whole plant possess antioxidant, anti-inflammatory, anti-arthritic, antipyretic and analgesic properties. In addition, the herb has demonstrated anthelmintic, laxative, diuretic and antimicrobial activity (Chakraborty 2010; Chakraborty & Roy 2010; Bose 2007). (Image courtesy Jeevan Jose, Wikipedia)

The roots of Cleome rutidosperma have an interesting medicinal reputation for the treatment of paralysis, epilepsy, convulsions, spasm and as an analgesic for pain relief (Chakraborty & Roy 2010). (Image courtesy Albert, Wikimedia Commons, CC-by-SA 3.0 Unported)

A Forgotten Herb: The Medicinal Pigweed Purslane can be counted among the most underutilised and undervalued of the Australian native herbs. It has an ancient history of use across the globe, although

Pigweed or Purslane is a heat and drought tolerant plant that is found throughout the Australian continent. It has an excellent reputation as an antiscorbutic that once led to its recommendation for the treatment of scurvy. The succulent leaves and stems have been a prized Aboriginal food item. The plant was collected, piled in heaps and left to dry – which allowed the seed capsules to ripen: ‘The seeds, after washing, were ground between stones and consumed raw. They are highly nutritious and keep the native in excellent condition’ (MacPherson 1930). (Image courtesy Ton Rulkens)

VALIDATING BUSH MEDICINES

Bee on Portulaca bicolor. Australia has an interesting diversity of Portulaca species, with around 23 being considered native – and an additional naturalised ornamental, Portulaca grandiflora. At least eight of the native species have not yet been botanically classified. (Image courtesy Craig Nieminski, flickr)

in many places it has been relegated to little more than a useless weed – which is even becoming locally endangered due to this misconception. It is a fairly unassuming-looking vegetable with gel-like qualities that are due to an arabinoglycan gum with emulsification properties similar to gum arabic. It can thus be effectively added to soups and stews as a thickening agent. This suggests diverse culinary and food processing uses for the plant – particularly as it has significant antioxidant and antimicrobial attributes (Irawan 2003). Purslane is also highly underestimated as a nutritional and medicinal resource. It is a good source of carbohydrate (40.7%), protein (23.5%) and fibre (8%), and is rich in vitamin C (ascorbic acid), β-carotene and B vitamins (particularly B1, B2 and folic acid). Vitamin E levels can be significant (ɑ-tocopherol 230 mg/g dry weight) and β-carotene levels in the leaves are also quite high (22–30 mg/g). Purslane has an extremely useful dietary fatty acid content (5.3%; 8.5 mg fatty acid per g net weight) that contributes omega-3 fatty acids, notably ɑ-linolenic acid (Aberoumand 2009; Xin 2008; Simopoulos 2004; Liu 2000). In comparison with other green leafy vegetables (mg/g), Purslane’s overall fatty acid level is high – for example, Spinach (1.7 mg), Buttercrunch Lettuce (0.6 mg), Red Leaf Lettuce (0.7 mg), Mustard greens (1.1 mg) (Simopoulos 2004). Australian studies have determined the following total fatty acid content for Purslane: fresh leaves (1.5–2.5 mg/g), stems (0.6–0.9 mg/g) and seeds (80–170

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mg/g). ɑ-linolenic acid was present at high levels (% total fatty acid content) in the leaves (60%) and seeds (40%) (Liu 2000). Purslane has the potential to be a very good mineral resource (mg/100 g) (Brand Miller 1993): • The whole plant is low in sodium, with higher levels of potassium (709–940 mg), magnesium (206–266 mg) and calcium (97–112 mg). • The root can have a much higher potassium content (1170 mg), with fair to good levels of magnesium (61 mg) and calcium (382 mg). •  Therefore, while a damper (bread) preparation would be low in sodium, the level of other minerals can be quite good: potassium, magnesium, calcium – as well as being high in iron (13–15 mg) and zinc (3–5 mg), and a low amount of copper. It is worth noting that the leaf and seed paste •  can be exceptionally high in iron (54 and 64 mg, respectively). There are a couple of other points of interest with regard to freeze-dried Purslane (Ward 2009): • A freeze-dried product retains good levels of protein and dietary fibre, with a low total fat content. • The caffeic acid content can be high – 2,632 mcg (mcg/g freeze-dried Purslane). • Ferulic acid (826 mcg) is present in good amounts, as are some other phenolics: quercetin (191.2 mcg), kaempferol (153.5 mcg), cyanidin (246.5 mcg).

In comparison with Purslane, Portulaca pilosa can be equally high in iron (5.5–38 mg) and potassium (500–1000 mg); with reasonable amounts of sodium (50–120 mg), magnesium (170–300 mg), calcium (265–300 mg) and some zinc (1– 1.7 mg) (Image courtesy Kim & Forest Starr, Hawaii)

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Purslane seeds. (Courtesy University of Missouri Extension)

The Sea Purslane (Sesuvium portulacastrum), which has an anti-scurvy reputation, has a very similar appearance to that of Portulaca pilosa – although the flowers tend to be a lighter lilac and it is restricted to seaside habitats (Images courtesy Kim & Forest Starr, Hawaii)

Purslane has been utilised for a remarkable variety of conditions: •  urinary tract disorders (dysuria, gonorrhoea, haematuria, dysuria, diuretic, urinary antiseptic); • inflammatory problems (mastitis, impetigo, erysipelas, eye inflammation); • infectious respiratory disorders (tuberculosis, whooping cough); • intestinal distress (gastritis, colitis, dysentery, worms); • as an effective healing antimicrobial agent (swelling, scalds, bruising, abscess, boils).

Many of these recommendations have been supported by studies that show a wide range of pharmacological attributes. Extracts of the herb have significant antiinflammatory, analgesic, antimicrobial, and wound healing properties.18 It also contains components that are active against schistosomiasis and leishmaniasis parasites19 (Dkhil 2011b; Irawan 2003). The antiparasitic properties of the plant could also be useful for treating intestinal worms (Quinlan 2002). In addition, extracts have shown a gastroprotective effect that would support the use of the remedy in stomach ulceration (Karimi 2004). The herb itself has a complex chemistry with diverse components being present.20 Purslane’s phenolic content (586 mg/100 g) can be associated with good antioxidant activity, which supports many of its medicinal uses (Yang 2009; Aberoumand 2008). Extracts have shown anti-inflammatory, renoprotective and hepatoprotective properties against drug-induced cellular damage that were linked with an antioxidant effect. It has shown interesting protective potential against liver damage due to the anticancer drug cisplatin. Indeed, the hepatoprotective activity of the herb extract was significant – and it has been utilised for treating viral hepatitis in China (Sudhakar 2010; Amida 2010; Al-Howiriny 2008; Elkhayat 18 Purslane contains the wound-healing agent allantoin and studies on the fresh plant have shown good wound-healing effects (Rashed 2004). Allantoin is an active ingredient of the wound-healing herb Comfrey (Symphytum officinale). 19 Other species of Portulaca also appear to have antiparasitic potential. P. hirsutissima and P. werdermannii have shown activity against Leishmania amazonensis, as well as immunomodulatory activity (Costa 2007). 20 Alkaloids, coumarins, organic acids (cinnamic, caffeic, malic and citric acids), anthraquinones, flavonoids (kaempferol, apigenin, myricetin, quercetin, luteolin), saponins, tannin, glutathione, glutamic and aspartic acids (see Rashed 2004 and Dweck 2001 for details).

VALIDATING BUSH MEDICINES

2008; Wang 2007). Polysaccharides are among the active components of Purslane extracts with antiviral (anti-herpes virus), immune-supportive, anti-stress and antioxidant activities. Interestingly, the herb can also improve exercise tolerance levels (Xiaojuan 2011; Dong 2010; YouGuo 2009). Additionally, Purslane has a reputation as a tonic in cardiovascular disorders including hypotension, palpitations and cardiac weakness21 (Irawan 2003). It has been suggested that the dietary use of Purslane could even be associated with a lower risk of heart disease and cancer due to its omega-3 fatty acid content – which would also be linked to an antiinflammatory effect. This, combined with the herb’s cholesterol-lowering potential and the presence of cardioactive glycosides and norepinephrine (i.e. noradrenaline, which has hypotensive effects) suggest further benefits for the cardiovascular system (Dkhil 2011b; Karimi 2010; Sanja 2009; Movahedian 2007; Simopoulos 2004; Ayodele 2005). Polysaccharide-based Purslane extracts have demonstrated significant antidiabetic activity (Gong 2009). The herb modulates cellular sensitivity to insulin, reduces glucose absorption and increases cellular glucose uptake. Clinical trials gave good responses, with the herb being marketed as an adjunct to antidiabetic therapy (Nutrition Care 2006). The woundhealing properties of Purslane may also be useful in counteracting the impaired healing responses of diabetic individuals (Laitiff 2010; Rashed 2003). (Image courtesy Nutrition Care, Australia) Aloe vera has a similar mucilaginous character to Purslane. It also has hypoglycaemic properties and good woundhealing effects, with significant potential benefits for diabetic individuals (Chithra 1998). (Image courtesy Solara Antara, flowersforhealing.com) 21 Levartenol, which is present in leaf extracts, has shown cardiotonic activity, leading to more vigorous contractions of the heart muscle. This compound can raise blood pressure and lower the heart rate (Dweck 2001)

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Purslane has long been used as a remedy for respiratory disorders, with studies confirming significant muscle-relaxant effects, with aqueous extracts possessing activity equivalent to that of the anti-asthmatic drug theophylline. These findings, plus its anti-inflammatory and antioxidant properties, support the traditional use of the decoction (boiled plant extract) as a bronchodilatory for asthmatic individuals – which has verified by clinical studies (Boskabady 2004; Malek 2004; Habtemariam 1993; Parry 1993, 1988, 1987; Okwuasaba 1986). In addition, the herb has antitussive properties (i.e. reduces the incidence of coughing) which were comparable to codeine (Boroushakei 2004). Purslane possesses substantial antimicrobial attributes that would complement its significant healing reputation: •  Plant extracts have good antifungal activity against dermatophytes (Trichophyton spp.) that are responsible for fungal skin infections (Oh 2000). •  The herb has good clinical activity in a fungal condition of the mouth known as oral lichen planus (the term ‘lichen’ referring to the lichen-like appearance of the infected area) (Agha-Hosseini 2010). •  Seed extracts demonstrated a high level of antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Pseudomonas aeruginosa, comparable to gentamicin. However, this activity appears to be quite specific as extracts had a low level of activity against Candida albicans and were inactive against Escherichia coli, Proteus vulgaris, Salmonella typhi and Aspergillus niger. • Other studies indicate that extracts can have a high level of activity against food-borne pathogens such as Staphylococcus aureus and Shigella dysenteriae. This supports numerous other traditional uses of Purslane, including its use as an antidiarrhoeal, antiphlogistic (anti-inflammatory) and bactericide for bacillary dysentery (Bae 2004; Yagoub 2006). The antibacterial properties of Purslane have also seen it recommended for the treatment of gonorrhoea (Dweck 2001). Various studies have shown that Purslane can affect the genitourinary system and fertility, including an inhibitory effect on male sperm formation. There is an extremely interesting clinical report regarding the

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efficacy of the seed powder for treating abnormal uterine bleeding conditions such as excessive menstrual bleeding and peri-menopausal bleeding (Shobeiri 2009; Verma 1982). Purslane extracts also possess anxiolytic, sedative and anticonvulsant properties. Herb extracts, as well as betacyanin components, have demonstrated substantial neuroprotective effects with potential benefits for memory function (Wang & Yang 2010; Chen 2009; Shobeiri 2009; Hongxing 2007; Wang 2007). Portulaca quadrifida is another medicinal species with an influence on central nervous system function with anticonvulsant properties. Extracts could facilitate recovery from seizures, as well as possessing sedative, analgesic and antifungal potential (Kamil 2010).

  Pigweed Pigments Portulaca grandiflora is a colourful garden ornamental with a very interesting history. The famous botanist William Jackson Hooker was the first to describe Portulaca grandiflora in 1829 after a South American excursion to the Rio Desaguardero. He admired ‘the rich purple hue, here and there marked with spots of an orange colour, from the orange-coloured variety which grew intermixed with the other’. Different varieties of the herb express specific amounts of betacyanin and betaxanthin pigments (betalains), with colours ranging from yellow and orange, to red and violet. White signifies an absence of pigmentation (Gerritson 2000). The yellow colour of Portulaca oleracea flowers is due to dopamine-betaxanthin (miraxanthin V), a pigment with fluorescent properties (GandíaHerrero 2009, 2005).   Betalains are a relatively unusual class of pigments that replace the more common anthocyanin phenolics. Flavonoids are commonly associated with flower colours, as well as colour variations in leaves, fruit and seeds. Betalains differ chemically and are of particular interest as food colourings – they have even been added to red wine to enhance its appearance. The most familiar is the rich burgundy pigment in beetroot, which belongs to the botanical order Caryophyllales – as do diverse other betalain-containing plants

Medicinally, Portulaca grandiflora, which is considered naturalised in Australia, has been utilised as a detoxicant herb for the relief of sore throat and skin rashes. Extracts have shown significant antimutagenic properties (Sriwanthana 2007; Liu 1990).

including spinach, cacti and Bougainvillea. Even the brightly coloured Amanita toadstools belong to this classification (Brockington 2011; Christinet 2004; Gerritson 2000).

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Buckthorn: A Native Source of Aesculin

Bursaria spinosa in flower. (Courtesy Brian Walters)

Amanita muscaria, the Fly Agaric, is a distinctly decorative fungus that contains a complex array of colouring substances that include betaxanthins, betacyanins, muscaflavins and seco-dopas. Among them are specific pigments for yellow (muscaflavin), red (muscarubrin), and red–purple (muscapurpurin) (Stintzing & Schliemann 2007).

The native Australian Buckthorn (Bursaria spinosa) is a small spiny endemic tree that is variously known as the Native Box, Box-thorn and Native Olive. The nectar-rich flower clusters can be used as a sweet bush snack. There are seven native species. Of these, Bursaria spinosa is found throughout much of the country – with the exception of Western Australia and the Northern Territory, where B. occidentalis is predominant. Queensland species include Bursaria incana and B. tenuifolia. Bursaria spinosa has two

Portulaca for Phytoremediation

Portulaca oleracea. (Courtesy Kim and Forest Starr, Hawaii)

Purslane is a good candidate for the revegetation of harsh drought-prone and saline environments. Indeed, the herb will remove and concentrate sodium and chloride from the soil, thereby having a substantial remedial effect (Hamidov 2007). In addition, Portulaca oleracea and P. tuberosa have metal-accumulation attributes (particularly for cadmium, chromium and arsenic) that suggest these species would be good choices for remediation of effluent-contaminated sites – surviving conditions that would seriously hamper the viability of many other plant species (Tiwari 2008). Purslane also has a good ability to remove bisphenol A (BPA) from water supplies. This compound, which has been in widespread use for the manufacture of plastics (PVC) and synthetic resins, has endocrine-disrupting properties that result in an oestrogenic effect. In a study of over 100 common garden plants, Purslane showed the best activity for quickly removing BPA from contaminated water. It may well be equally useful for phytoremediation involving other phenol-based endocrinedisrupting agents such as the steroid hormone oestradiol, and 2,4-dichlorophenol (an intermediate in the production of the herbicide 2,4-D) (Imai 2007).

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subspecies (lasiophylla and spinosa) that are found in southern Queensland, ranging to the more temperate climates of New South Wales, South Australia, Victoria and Tasmania. New South Wales has a couple of unique species – Bursaria longisepala from the Blue Mountains, and B. calciocola from the Wombeyan Caves Reserve. In addition, there is a rare species in central Queensland, Bursaria reevesii, which is restricted to only two sites.

Horsechestnut (Aesculus hippocastanum). However, this does not mean that local Australian resources should be simply discarded – particularly a product that has such excellent market potential.

Ripe horsechesnut conkers. Horsechestnut seed extract has traditionally been regarded as a valuable ‘tonic’ astringent and there is a substantial amount of support for this recommendation. The remedy has a significant strengthening effect on the venous system. The active principle is a complex of around 30 individual compounds (triterpene oligoglycosides) that form a saponin-based mixture usually referred to as aescin, with 3–6 per cent present in the seed, as well as flavonoids and lipids. In much of the older literature this mixture was known as aesculetin (the glucoside of which is aesculin, also spelt esculin). However, most recent studies have utilised Horsechestnut extracts (HCE), standardised to contain around 70 per cent aescin (escin) (Sirtori 2001). This is an important distinction because the terms utilised in this work are as per the original papers. (Image courtesy Bob Gibbons/Arkive)

  Early investigations into the chemistry of Buckthorn Bursaria occidentalis. (Courtesy Bernhard Jacobi, flickr)

Buckthorn is illustrative of an Australian native plant with great medicinal potential, but little backing for practical development. Despite the fact that the tree has generally been regarded as a nuisance and a weed, Buckthorn has worthy potential as a natural product resource. It contains a saponin-based substance named aesculin (or esculin) that is particularly useful for venous circulatory problems such varicose veins and haemorrhoids. In 1980 a Sydney company began the export of aesculin extracted from Buckthorn to Europe. Three years later the venture collapsed. Unfortunately, the price of the product was not competitive enough against the yield of the European

determined that: ‘Very little aesculin is found in the twigs and branches, but from the leaves 4 to 5% of the compound may be obtained. Most of the commercial supply of aesculin seems to come from NSW, whence small amounts are exported. Through its ability to absorb strongly in the ultra-violet region, aesculin is commonly employed in preparations designed to protect the skin from sunburn. Another use of aesculin is as a test-substance in microbiology where certain organisms are identified by their ability to break down the substance’ (McKern 1960). Aesculin has also been utilised for the treatment of an ulcerous autoimmune skin condition known as lupus. In 1949 Dr Nancy Atkinson demonstrated Bursaria leaves had antibiotic properties which were active against Staphylococcus aureus.

VALIDATING BUSH MEDICINES

Professor EH Rennie originally discovered that aesculin was present in Buckthorn in 1889. At that time, the apparent ability of the leaves to impart a distinctive blue colour to the Blue Lake had attracted a fair amount of curious enquiry: Those of us who hail from South Australia are familiar with the description of the Blue Lake near Mt. Gambier. On the bank of the lake, as well as in many other parts of South Australia, there is an abundant growth of a shrub known as Bursaria spinosa, Pittosporaceae, the leaves of which if placed in water communicate to it a blue fluorescence, and it has been suggested that the lake owes its blue colour to the leaves which fall into it. I doubt very much whether that is the true explanation, but, be that as it may, I have been able to show that the leaves contain a well-known glucoside, aesculin, occurring in the bark of the horse-chestnut, and which imparts a blue fluorescence to water (Rennie 1926).

Blue Lake mid-December. The Blue Lake is around 75 metres deep and fills an extinct volcanic crater. The water changes colour from grey to a vivid blue in November, gradually fading to a winter grey by mid-year. The explanation lies in chemical changes involving the formation of microcrystals of calcium carbonate during the warmer weather. This has an effect on light penetration and diffraction in the water that result in scattering the blue light wavelength. In addition, microscopic organisms that may exert an influence on the colour scheme are present. (Image courtesy Aaron Allen)

The saponin mixture aescin (or escin) has a range of valuable medicinal attributes. Recent literature differentiates between ɑ-aescin and β-aescin, with β-aescin considered to be the pharmacologically active component. Studies have shown antiviral, antioxidant, anti-inflammatory, anti-oedema, immunosuppressive, and analgesic properties – as well as protective effects in some forms of gastric ulceration and liver damage. In addition, investigations have indicated interesting

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anti-arteriosclerotic, radioprotective, neuroprotective and anticancer potential (Li 2012; Atmaca 2011; Ji 2011; Jiang 2011; Lee 2011a, 2011b; Murat Bilgin 2011; Tien 2011; Yun 2011; Rios 2010; Barber 2009; Yalinkilic & Enginar 2008; Zhao 2008; Lee 2002; Sirtori 2001; Lin 2000; Gilani 1998; Martin-Aragon 1998; Matsuda 1997; Galabov 1996; Martin 1991; Kabelitz & Al-Gorany 1989; Tubaro 1988). Horsechestnut seeds are a major source of aescin saponins. The remedy has traditionally been utilised as a tonic for venous problems, including haemorrhoids. Research has verified many of its traditional recommendations – an ever-expanding body of knowledge that continues to suggest far wider clinical applications with rather remarkable potential. There are numerous clinical studies that support the use of Horsechestnut seed extracts in chronic venous insufficiency (Altern Med Rev 2009; Leach 2006; Suter 2006; Dickson 2004, Pittler & Ernst 2004, 1998). Not only is the inherent anti-inflammatory effect of the remedy extremely useful, there are cartilageprotective properties that help to facilitate the healing process in traumatic injury. A number of proposals have therefore examined its potential benefits in osteoarthritis and rheumatoid arthritis (Elliott 2001; Watanabe 1999; Yamada 1999). Aescin may even have a synergistic anti-inflammatory effect in combination with corticosteroids, thereby potentiating the drug’s clinical usefulness (Xin 2011a). Investigations into the biochemistry of the European Horsechestnut (Aesculus hippocastanum) have offered many new insights into the therapeutic value of aescin. This compound’s potential for the reduction of post-operative trauma is truly impressive: alleviating inflammation, oedema and tissue damage, promoting wound healing and reducing the incidence of adhesions. It has even demonstrated modification of ischaemic brain damage (Zhang 2011, 2010; Harikumar 2010; Wang 2009; Fujimura 2006a; Fu 2005). This protective effect on brain tissue may have more extensive benefits as aescin has shown neuroprotective effects against organophosphateinduced cerebral oedema (Wang 2011). Clinically, aescin injections have been utilised to minimise the traumatic effects of accidents resulting in severe head injuries and for the prevention of deep vein thrombosis following surgery – as well as possessing interesting vascular-protective properties suitable for

a;

b:

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use during heart surgery (angioplasty) to prevent tissue injury (Kwon 2011; Pan 2003; Sirtori 2001; Huang 1993). Additionally, Horsechestnut and aescin have been employed in the treatment of Bell’s palsy, dysmenorrhoea, carpal tunnel syndrome, back injuries and intervertebral disc lesions (Sirtori 2001; Morgan & Bone 1998). Esculetin has also been investigated for treating eye disorders due to ischaemia (reduced blood flow) and inflammation (Liu & Chiou 1996; Gupta 1993).

Indian Horsechestnut. In addition to the European Horsechestnut, other species of Aesculus can be utilised as aescin resources. Indeed, the content of the Indian Horsechestnut (A. indica) seeds (13.4% weight/weight [sic]) was higher than that of A. hippocastanum (9.5%) (Srijayanta 1999). A formulation of sodium aescinate has shown significant anti-inflammatory and antioxidant cellular-protectant effects against lung injury due to endotoxin exposure and methyl parathion (Du 2011; Xin 2011b). This extremely hazardous cholinerase-inhibitory insecticide was once widely used for agricultural crops, mainly rice, cotton and fruit trees. It has also been employed in chemical warfare – and is now banned in many countries. The product (pictured) was outlawed in Germany in 2002 and this bottle shows explicit warnings as to its toxicity. (Image courtesy Mr Checker, Wikimedia Commons, CC-by-SA 3.0 Unported)

There is good potential for aescin to assist recovery from paralytic ileus, a post-operative complication of abdominal surgery – as it was effective at helping to re-establish gastrointestinal mobility (Xie 2009). Other benefits for gastrointestinal disorders may be linked to an inhibitory effect on Escherichia coli survival in the gut, which supports its use as an antidiarrhoeal remedy. Studies have also suggested

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 Horsechestnut: The Extraordinary Clinical Potential of a Traditional Venous Tonic

Horsechestnut: tree and flowers.

Sand flies of the genus Phlebotomus are very small bloodsucking insects that are vectors for parasitic diseases, including leishmaniasis. Aescin has anti-leishmanial properties that show clinical promise. Recent investigations have focused on effective drug delivery systems such as encapsulation of the saponin in colloidal carrier nanoparticles that maximise its efficacy (Van de Ven 2012a, 2012b, 2011). (Image courtesy World Health Organization, Geneva, Switzerland, and CDC, USA)

a beneficial role as an anti-inflammatory agent for treating colitis (Witaicenis 2010; Duncan 2004). More recently, the discovery of an antiobesity effect for esculetin has shown positive effects on cholesterol levels and fat absorption (Avci 2010; Shin 2010; Hu 2008). Another commercial avenue for the use of aescin involves the cosmetic industry. Its healing, anti-inflammatory and anti-oedema properties make it well suited for incorporation into a range of cosmetic formulations. Studies showing antioxidant, UV-protective, anti-melanoma and anti-ageing effects have added extra support for its use (Lee 2007; Fujimura 2006a, 2006b; Tahara 2005).

Horsechestnut’s highly effective anti-oedema and veno-protective activities can significantly ameliorate vascular damage. The remedy is particularly well suited for conditions where a slow, progressive venous tonic effect is required. Horsechestnut can therefore be beneficial for a wide range of disorders, ranging from chronic venous problems (varicose veins, lower limb oedema and haemorrhoids) to surgical wounds or injuries characterised by swelling and venous congestion. Clinical studies have verified that there can be substantial improvement in chronic venous insufficiency, with gradual resolution of pain, tiredness, tension, leg swelling, itching and oedema (Luzzi 2011; Altern Med Rev 2009; Pittler & Ernst 2004; Siebert 2002; Ottillinger & Greeske 2001; Morgan & Bone 1998).

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Horsechestnut has also been utilised for the treatment of asthma and bronchitis (Morgan & Bone 1998). The anti-inflammatory, bronchodilatory and expectorant effects of the remedy would certainly assist in relieving respiratory distress. Experimentally, β-aescin has shown potent lung-protective and anti-allergic attributes that can reduce airway inflammation (Xin 2011a; Lindner 2010; Mabalirajan 2009). In acute injuries, the local application of various preparations (wash, ointment or cream) has been used to resolve bruising and reduce tissue oedema (swelling). Therefore the remedy can be effective for treating sports injuries, dental surgery, gynaecological and obstetrical venous problems. However, it should not be applied to open wounds as there is a possibility that the saponins may be directly absorbed, which can result in gastrointestinal upset (Morgan & Bone 1998). Overall, the incidence of side-effects associated with the use of Horsechestnut seed preparations is extremely low. Refinements in the quality of aescin-containing extracts have resulted in a high degree of efficacy and they are extremely safe in clinical practice. One report examining over 900 million individual doses of a standardised extract revealed that only 15 patients complained of side-effects – an impressive safety record (Morgan & Bone 1998). There are, however, occasional reports of gastrointestinal discomfort, dizziness, headache and skin itching (Altern Med Rev 2009). This has been associated with the use of refined products, and is probably because modern manufacturing methods tend to produce products with a high level of purity that permit the use of quite high doses. Furthermore, a few incidents of anaphylactic (severe allergic) reactions due to the topical application of aescin are on record. There have been rare reports of poisoning with Horsechestnut seeds that were linked to the presence of a toxic principle called esculoside – which is now removed in the production of standardised extracts (Sirtori 2001). The anti-tumour potential of Horsechestnut is an interesting facet of the remedy that has been

evaluated by a number of studies. Esculetin is a strong antioxidant and antimutagenic agent that has shown anticancer activity in breast cancer cells. Studies have also suggested that a number of phenolic compounds (i.e. esculetin, ellagic acid22, catechin, propyl gallate, esculin) may help in the prevention of lung cancer due to tobacco smoke (Yang 2010, 2006; Kim 2008; Bryja 2003; Wang 2002; Chu 2001; Kawaii 2000, 2001; Hecht 1999; MartinAragon 1998; Matsunaga 1998, Miller 1996; Sharma 1994; Kitagawa & Noguchi 1994; Noguchi 1995, 1993; Teel & Castonguay 1992; Konoshima & Lee 1986). Recent investigations have an expanded scope which suggests anticancer potential for aescin in colon and liver cancer cells, cholangiocarcinoma cell lines, oral cancer, leukaemia and multiple myeloma (Park 2011; Shen 2011; Zhang 2011; Park 2010, 2008; Harikumar 2010; Tan 2010; Kok 2009; Zhou 2009; Lin 2009; Kaneko 2007, 2004, 2003; Patlolla 2006). The potential use of escin to potentiate drug treatment (gemcitabine) in pancreatic cancer studies has attracted recent interest as this condition is very resistant to treatment (Wang 2012). Other, equally interesting, aspects of the pharmacological properties of esculetin appear extremely useful from a clinical point of view. Esculetin has shown potentiating effects on the anticancer activity of 5-fluorouracil, taxol and cisplatin, as well as an ability to protect against renal toxicity and immunosuppression (Tikoo 2011; Ming 2010; Kuo 2006). This renoprotective effect may extend to benefits for diabetic individuals and HIV treatment protocols (Surse 2011; Grases 2004). Aescin has also shown experimental hypoglycaemic activity that may contribute to its value (Yoshikawa 1996, 1994). In addition, studies have suggested aescin, in combination with troxerutin (a flavonoid with vasoprotective properties23), has benefits for inner ear problems and associated hearing loss (Siegers 2008). 22 In some studies the antimutagenic and anticancer agent ellagic acid was shown to be more effective than esculetin or esculin in inhibiting lung tumours (Boukharta 1992). 23 Troxerutin (a rutin derivative) which has been isolated from the Japanese Pagoda Tree (Sophora japonica), has been marketed as an antithrombosis agent. Experimentally, this flavonoid has shown protective effects on brain function that may be useful for diabetics and some forms of memory disorder (Lu 2010). Clinical trials suggest that a combination with products such as pycnogenol or coumarin provide substantial benefits for venous insufficiency (Riccioni 2004; Vanscheidt 2002). One clinical study showed enhanced post-surgical recovery following haemorrhoid resection, when used in combination with the antihaemorrhagic agent carbazochrome (Basile 2001).

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 Esculetin: Traditional Herbal Resources

Fraxinus rhynchophylla bark. (Courtesy Dalgial, Wikimedia Commons, CC-by-SA 3.0 Unported)

Chinese studies of coumarins sourced from Fraxinus cortex (Fraxinus rhynchophylla24, Oleaceae family) have indicated that esculetin and esculin have beneficial effects on hyperuricaemia and renal dysfunction (Li 2011). The herb is traditionally utilised as an expectorant, antitussive, anti-asthmatic, antidiarrhoeal agent, as well as being considered useful for cataract and liver dysfunction (Yeung 1985). Recent studies have established hepatoprotective anti-fibrotic effects on liver cells that suggest its use for the treatment of viral hepatitis. The esculetin content of the extract was quite high (33.54 mg/g) – and its antifibrotic activity was superior to that of the Milk Thistle. The closely related Fraxinus excelsior has equally significant medicinal properties with studies indicting antioxidant, antirheumatic, anti-inflammatory, analgesic and antipyretic activity. The seeds are a potent hypoglycaemic and hypotensive agent (Tien 2011; Peng 2010). 24 Qin-pi (Chin-pi) from Fraxinus bark can also be sourced from Fraxinus bungeana – although there are other substitutes such as F. stylosa, F. chinensis or F.chinensis var. acuminata.

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The presence of aesculetin (or aescin/escin) in other herbal products may have similar benefits. Its liver-protective effects may well be important in the activity of various herbs traditionally utilised for treating liver disorders – such as Chicory (Cichorium intybus) and Bougainvillea spectabilis. Esculetin has also been identified as an antimutagenic agent in Alchemilla speciosa, while esculetin and scolymoside were the active antioxidant components of Artemisia montana (Kim 2000; Schimmer & Eschelbach 1997).

Artemisia capillaris. Esculetin, which has important antioxidant and anti-inflammatory properties, is present in a number of Artemisia species (e.g. A. capillaris, A. montana, A. scoparia) that have been traditionally utilised for treating skin inflammation and/or liver disorders (Kwon 2011; Pan 2003; Kim 2000). (Image courtesy Wayne Cheng, flickr)

 Xanthine Oxidase: An Inflammatory Enzyme

‘The Gout’ by James Gillray, published 14 May 1799.

Gout is a form of acute inflammatory arthritis that most frequently affects the big toe – although the condition is not confined to this

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joint and more systemic manifestations can affect other joints (heel, knee, wrist, fingers) with the formation of trophi (uric crystal accumulations). This can, at times, affect the kidneys with the development of renal stones (urate nephropathy) also resulting from a reduced excretion of uric acid (hyperuricaemia). Gout sufferers can also experience fever and fatigue. The condition tends to be associated with dietary triggers such as alcohol, fructose sweeteners, meat and seafood, as well as various forms of trauma (including surgery) and some drug therapies (e.g. niacin, aspirin, immunosuppressant drugs and some diuretics). The use of vitamin C and coffee are among the dietary strategies that help to reduce the incidence of the condition.

Crystallographic structure (monomer) of xanthine oxidase from bovine milk. This is a complex compound, with the colours indicative of different components: bounded flavin molecules (FAD, in red), ferridoxin-iron sulfur clusters (Fe-S, in orange), molybdenum atoms (molydopterin cofactors, in yellow) and salicylate (blue). (Image courtesy Yikrazuul, Wikimedia Commons, CC-by-SA 3.0)

Gout is an inflammatory condition that involves the action of an enzyme, xanthine oxidase, which is involved in the production of uric acid crystals from xanthine and hypoxanthine. Gout is often (but not always) characterised by raised uric acid levels (hyperuricaemia). It is treated with painkillers, anti-inflammatory drugs

(NSAIDs), steroids, colchicine (which is specific for gout), and xanthine oxidase inhibitors such as the drug allopurinol. Xanthine oxidase is normally present in the liver and blood levels may be raised in cases of fairly severe liver damage. Additionally, xanthine oxidase may be involved in cardiovascular disorders and oxidative eye damage. Studies of natural products with potential for the treatment of gout have indicated that aesculin injections could reduce serum urate levels (salts of uric acid) in animals. Strangely enough, this hypouricaemic effect was not linked to xanthine oxidase activity – even though esculetin has shown inhibitory effect on this enzyme (Lin 2008; Kong 2002; Chang & Chiang 1995).

Berry fruits, and cherries in particular, have been shown to have excellent anti-gout and anti-arthritic properties (Kelly 2006; Jacob 2003). The effective dose appears to vary from 6 cherries (around 50 g) to 200 g, which effectively lowers uric acid levels and prevents gouty ‘flare-ups’ – an effect due to the anthocyanidin components that inhibit xanthine oxidase activity. Canned or frozen berries are equally as effective as the fresh fruit. Other berry fruits that appear to be useful include Hawthorn, Blueberry, Cranberry and possibly even Strawberry, although they have to be the dark, rich-coloured varieties.

VALIDATING BUSH MEDICINES

A Renewed Interest in Native Flora

The clinical value of the Australian flora is quite evident from the preceding discussion, which has provided numerous illustrations of the practical value of traditional herbal medicines – and their continued role as therapeutic agents. In addition, there have been various efforts aiming toward a more extensive evaluation of native plant chemistry (phytochemistry). Some species have shown excellent practical value, leading to some unique Australian products reaching the marketplace. The antimicrobial and aromatic properties of Lemon Myrtle and Tea-tree oils are among the most successful of these. However, there are many other plants with innovative pharmaceutical potential about which we know very little – although what we do know can engage one’s curiosity.

A unique range of balms sourced from native Australian plants. (Courtesy Australian Native Therapies)

Backhousia citriodora is highly rated as an Australia aromatic medicinal herb with a broad spectrum of antibacterial activity. Its wonderful fragrant qualities make it an excellent candidate for use in diverse cosmetics and skin-cleansing products – and for treating unsightly skin problems such as acne and blemishes, as well as numerous forms of skin irritation (including psoriasis), fungal problems (e.g. tinea) and some viral infections (notably molluscum contagiosum) (see Volume 1 for further details). (Image courtesy Lemon Myrtle Essentials)

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  Phytochemical evaluations of the flora have resulted

in a number of discoveries with intriguing medicinal potential. Antiviral agents such castanospermine (and derivatives) from the Blackbean (Castanospermum australe) and prostratin25 from the Milky Mangrove (Excoecaria agallocha) have been seriously investigated for use in the treatment of HIV. Many species of the endemic genus Eremophila contain unqiue diterpenes with antimicrobial properties, which include an activity against drug-resistent strains of bacteria. There are also recent innovative developments with regard to the use of Bastard Sandalwood oil (Eremophila mitchellii) as a termiticide (see Chapter 7). There are some instances where Australian initiatives have extended beyond the endemic flora. Indeed, numerous Euphorbia species (both native and naturalised) have equally interesting antibacterial potential. The latex of a few species also acquired a reputation as an effective skin cancer treatment – a folk remedy that appears to have excellent clinical potential. In particular the Radium Weed or Milkweed (Euphorbia peplus), which was introduced into Australia in the early 1800s, provided a well-known local remedy for warts, corns, waxy growths, sun cancer and rodent ulcers. Joseph Maiden commented: ‘it is stated that the natives of the Northern Territory use the juice of a species of Euphorbia as a specific in smallpox. Another species affords a juice said to be a remedy in cancer. Without committing oneself to an expression of opinion as to the utility of the Euphorbias alluded to, our native species will doubtless well repay a thorough examination of their medical properties’ (Maiden 1889). More than a century later, investigations of Radium Weed by an Australian company, Peplin Biotech Pty Ltd, have produced a cream formulation for clinical use. In 2001, the Executive Summary of a Rural Industries Research and Development Corporation (RIRDC) report on the plant’s medicinal potential by Davis and Parsons commented: ‘An early clinical trial on thick and thin non-melanoma skin cancers has confirmed that the compounds are very effective in producing long-term (possibly permanent) responses in human patients without any evident systemic toxicity when applied topically. This 25 Prostratin was originally isolated from the New Zealand plant Pimelea prostrata. It is also present in the Samoan tree Homalanthus nutans and some medicinal Euphorbia, notably the Chinese herb E. fischeriana (Tang 2012).

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is highly significant because current topical methods of drug treatment require long periods of application without being fully effective, and physical methods (e.g. surgery) are expensive and difficult to apply to the large areas affected, especially in older people.’ High praise indeed.

In a review of 39 native plants (from which 56 extracts were prepared), Euphorbia australis (whole plant) was the only species active against both gram-negative and grampositive bacteria (Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhimurium) – albeit the inhibitory action was incomplete. Numerous Euphorbia species have long been utilised as antibacterial and healing agents. In Australia, E. australis has been employed as a medicinal wash for skin sores – as was E. drummondii (pictured here), which was also considered useful for genital sores, fevers, and as an antidysentery remedy (Palombo & Semple 2001). (Image courtesy Howard Rawson, flickr)

Euphorbia peplus. (Courtesy Kim & Forest Starr, Hawaii)

Euphorbia hirta, which is widely naturalised throughout the continent, is also considered to have anticancer and antiviral (anti-HIV) properties worthy of commercial development (Davis & Parsons 2002).

Table 3.2 Overview of Australian Plants Examined for Biological Properties in Recent Scientific Literature that are of Interest for Medicinal Purposes Notes: 1. See Volume 1 for Santalum and Syzygium. 2. See Volume 2 for Acacia, Eucalyptus, Leptospermum and Melaleuca. Essential oils are not included here as they are 3.  discussed in detail under individual plant species in each volume. 4. There is a comprehensive review focusing on the CSIRO phytochemical studies that provides details of alkaloidal substances in the native flora, as well as anti-tumour studies. This has been published in Plants for Medicines by DJ Collins and colleagues (1990). 5. A review of tropical rainforest plants from Northern Queensland lists 23 extracts with antimicrobial activity and 27 extracts with cytotoxic activity. Only the main results are included in this table (Setzer 2001).

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Table 3.2 Overview of Australian Plants Examined for Biological Properties in Recent Scientific Literature that are of Interest for Medicinal Purposes Species Acacia aulacocarpa Acacia complanta Adansonia gregorii Ajuga australis Allocasuarina littoralis Araucaria bidwillii (see also Volume 2) Asteromyrtus symphyocarpa Asteromyrtus shepherdii Amyema quandong

Astrotricha longifolia

Traditional medicinal use (if any) Investigations (reference) Leaf: antibacterial, more active against gram-positive bacteria (Cock 2012b). Leaf: antifungal against Aspergillus niger (Cock 2012b). Flower: limited activity; antibacterial against Bacillus subtilis (Cock 2012b). Flowers: antimicrobial (Cock 2008a). Extracts: acaricidal activity; extracts and ajugarin I showed strong insect antifeedant activity against Plutella xylostella (Rasikari 2007). Leaves: broad-spectrum antibacterial, particularly good activity against gram-positive bacteria (Cock 2008a, 2008b, 2008c). Bunya Nut extracts: good broad spectrum of antibacterial activity (Vesoul & Cock 2012). Use: headache, aches and pains. Leaves: anti-migraine potential (Rogers 2000). Bark: antiviral (anti-HSV) activity (Setzer 2001). Use: Feverish conditions. Leaves: antibacterial, active against drug-resistant bacteria (Palombo & Semple 2002; Palombo 2001). Leaves: antimicrobial (Cock 2008a). Leaves: antimicrobial (Cock 2008a).

Backhousia citriodora (see also Volume 1) Banksia collina

Leaves: antimicrobial (Cock 2008a).

Balanops australiana

Bark: antiviral (anti-HSV) activity (Setzer 2001).

Beyeria lechenaultii Boronia spp.

Use: general sickness and fevers. Aerial parts: antibacterial (Palombo 2001). Alkaloids and flavonoids from four species: antibacterial activity (Nazrul Islam 2002).

Brachychiton acerifolius

Flowers: antimicrobial (Cock 2008a).

Buckinghamia celsissima Callistemon citrinus

Leaves: significant bread-spectrum antibacterial activity; antifungal against Candida albicans and anti-yeast against Saccharomyces cervisiae (Cock 2009a, 2008a). Leaves and flowers: antimicrobial (Cock 2008a).

Callistemon salignus

Leaves and flowers: antimicrobial (Cock 2008a).

Casearia grayi

Stem: antimicrobial, antioxidant. Leaf: antioxidant, cytotoxic (Mosaddik 2004). Root: antimicrobial. Leaf: antioxidant. Stem: cytotoxic (Mosaddik 2004). Leaf: high antioxidant activity (Mosaddik 2004).

Casearia multinervosa

Casearia sp. (Mission Beach) Carissa lanceolata Castanospermum australe Centipeda cunninghamii

Ceratanthus longicornis

Use: chest pain, toothache, colds, flu, rheumatic pain; insect repellent. Root: antibacterial activity (Hettiarachchi 2009). Use: toxic properties, seeds processed and used as food. Seeds: anti-HIV activity; isolation of castanospermine (Roja & Heble 1995). Use: coughs, colds, skin infections. Extracts: anti-inflammatory, antioxidant; skin-healing, rehydrating and cellular protective activity (see page XX). Leaf and stem: acaricidal activity; low cytotoxicity (Rasikari 2005).

Clematis pickeringii

Stem: anti-inflammatory (Li 2005, 2003).

Clerodendrum floribundum

Use: aches and pains, headache, skin complaints, infected or inflamed eyes, diarrhoea, bronchial congestion. Xanthine oxidase inhibitory activity (Sweeney 2001).

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Clerodendron traceyi

Leaf and stem: acaricidal activity (Rasikari 2005).

Conospermum incurvum Conospermum brachyphyllum Cryptocarya corrugata

Conocurvone, antiviral (anti-HIV) activity (Cannon 1999; Dai 1994).

Cymbopogon ambiguus

Dianella callicarpa

Use: respiratory tract infections, headache, fever, skin disorders, eye wash. Leaf: weak antiviral against Ross River virus (Semple 1998). Whole plant: anti-migraine potential (Rogers 2001). Root: significant antimicrobial and antiviral activity (Dias 2009b).

Dianella longifolia var. grandis

Roots: antiviral against poliovirus (Semple 2001, 1998).

Dianella revoluta var. revoluta Doryphora sassafras (see also Volume 1) Drypetes lasiogyna

Use: colds, general sickness. Roots: weak antiviral against human cytomegalovirus (Semple 1998). Use: highly aromatic; tonic. Alkaloid-rich bark: alkaloid with antimalarial activity isolated (Buchanan 2009). Bark: antiviral (anti-HSV) activity (Setzer 2001).

Eremophila

Numerous species have antimicrobial properties (for details of chemistry see Chapter 7).

Erythrina vespertilio

Glossocarya calcicola

Use: headache, sore eyes; sedative. Bark: anti-migraine potential (Rogers 2001). Use: skin sores, medicinal wash; cancers, stimulate milk flow (lactagogue) Whole plant: antibacterial (Palombo 2001) Whole plant: antiviral against human cytomegalovirus (Semple 1998) Use: skin sores, genital sores, fever, rheumatism, warts, anti-diarrhoeal (dysentery, chronic diarrhoea). Whole plant: weak antiviral against human cytomegalovirus (Semple 1998). Use: mashed bark infusion rubbed over skin to ease pain, or for ‘sickness’ (Roth 1903); sap or leaf decoction widely used to treat ulcers. Twigs and bark: contain prostratin, which has antiviral (anti-HIV) potential. Use: inflammatory disorders, mumps, smallpox, gonorrhoea, bleeding disorders (haematuria, haemoptysis, menorrhagia). Bark: anti-inflammatory (Li 2003). Leaf extract: strong cytotoxic activity; clerodane triterpenes isolated (Rasikari 2007).

Grevillea juncifolia

Leaves and flowers: antimicrobial (Cock 2008a).

Grevillea pteridifolia

Grevillea striata

Endophyte (NRRL 30566): This strain of Streptomyces produces novel antibiotics (kakadumycins). Kakadumycin A has broad spectrum of antibiotic activity, especially against gram-positive bacteria, and impressive activity against malaria parasite (Plasmodium falciparum) (Castillo 2003). Leaves and flowers: antimicrobial (Cock 2008a). Phenolic compounds isolated with potential cardiovascular activity (Roufogalis 1999). Phenolic compounds isolated with potential cardiovascular activity (Roufogalis 1999).

Haemodorum simplex

Bulb and aerial parts: antibacterial, antifungal, antiviral studies (Dias 2009a).

Ipomoea pes-caprae subsp. brasiliensis Isotoma petraea

Use: headache, aches and pains, marine stings. Whole plant: anti-migraine potential (Rogers 2000). Use: Respiratory disorders. Whole plant: weak antiviral against Ross River virus (Semple 1998). Leaves: antimicrobial (Cock 2008a).

Euphorbia australis

Euphorbia drummondii

Excoecaria agallocha

Ficus racemosa

Grevillea robusta

Jacksonia scoparia Kennedia nigricans (misspelt K. nigriscans in the original research paper) Lepidosperma viscidum

Leptospermum petersonii (see also Volume 2)

Bark: antiviral (anti-HSV) activity (Setzer 2001).

Leaf endophyte (Streptomyces) with antibacterial, anti-mycobacterial and anti-malarial (anti-plasmodial) activity; antibacterial compounds (munumbicins) identified (Castillo 2006, 2002). Use: colds. Stem base: antibacterial; active against drug-resistant MRSA (Tomlinson & Palombo 2005; Palombo & Semple 2002; Palombo 2001). Essential oil: antifungal against dermatophytes (Park 2007).

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Macadamia integrifolia

Flowers: antimicrobial (Cock 2008a).

Mirbelia oxylobiodes

Leaves and flowers: antimicrobial (Cock 2008a).

Morinda citrifolia Neolitsea dealbata

Use: wounds, ulcers, antiseptic. Fruit powder: anti-inflammatory (Li 2003). Bark: antiviral (anti-HSV) activity (Setzer 2001).

Pittosporum hirtellus

Extracts: in vitro antiviral activity, but was not active in vivo (Shead 1992).

Pittosporum phylliraeoides var. microcarpa (see also Volume 1)

Plectranthus habrophyllus

Use: colds, coughs, skin complaints; also as anticancer agent. Fruit, wood, leaves: antiviral against Ross River virus (Semple 1998). Dried plant material: broad spectrum of antibacterial activity; antifungal against nystatin-resistant Aspergillus niger (Cock 2011). Leaf extracts: experimental tumour cell inhibition; cytotoxic and immun stimulation (Lindquist 2007). Use: antiseptic; wounds, ulcers, sores; itching skin disorders (prickly heat), chicken pox. Leaves: anti-mycobacterial activity (McRae 2008). Acaricidal activity against mites (Tetranychus urticae). Other species had acaricidal potential including P. graveolens (Rasikari 2007). Leaf and stem: acaricidal activity (Rasikari 2005).

Plectranthus sp. (Hann Tableland)

Leaf and stem: acaricidal activity; low cytotoxicity (Rasikari 2005).

Podocarpus grayae

Bark: antiviral (anti-HSV) activity (Setzer 2001).

Premna serratifolia

Leaf and stem: acaricidal activity; low cytotoxicity (Rasikari 2005).

Prostanthera rotundifolia

Aromatic fragrant herb. Essential oil: antifungal activity against Botrytis cinerea, a grape pathogen of vineyards (Antonov 1997). Use: colds, respiratory infections, skin sores, eye complaints. Aerial parts: antiviral against poliovirus, flavonoid active against picornaviruses (Semple 1999, 1998). Aerial parts: anti-mycobacterial (Meilak & Palombo 2008). Use; colds, flu, sore throat, venereal disease, dysuria. Leaves: antibacterial (Palombo 2001).

Planchonia careya Plectranthus diversus

Pterocaulon sphacelatum

Santalum lanceolatum (see Volume 1 for a review of Australian Santalaceae) Scaveola spinescens Scolopia braunii Stemodia grossa Syzygium australe (see also Volume 2) Syzygium luehmannii Tasmannia lanceolata

Terminalia ferdinandiana (see also Volumes 1 & 2) Tinospora smilacina Xylosma terrae-reginae

Use: boils, skin sores, gastrointestinal disorders, urinary problems. Stems and leaves: antiviral against human cytomegalovirus (Semple 1998). Stem: antimicrobial, antioxidant. Leaf: antioxidant, cytotoxic (Mosaddik 2004). Use: colds, rheumatism, headache. Xanthine oxidase inhibitory activity (Sweeney 2001). Leaves: good broad-spectrum antimicrobial activity; also antifungal activity against Aspergillus niger (nystatin-resistant strain) (Cock 2012, 2008a). Leaves: minor antibacterial activity (Cock 2012). Use: flavouring, spice. Pepperberry extracts and polygodial have shown antioxidant and gastroprotective properties (Netzel 2006; Matsuda 2002); polygodial has substantial antibacterial and anti-candida activity, as well as anti-inflammatory, analgesic, cytotoxic and anti-allergic properties (Kubo 2005, 2001; da Cunha 2001). Fruit: strong antioxidant activity; high levels of vitamin C, phenolics (including gallic and ellagic acids) and anthocyanins (Mohanty & Cock 2012). Fruit pulp extracts: good broad-spectrum antibacterial activity (Cock & Mohanty 2011). Use: catarrh, colds, cough, diarrhoea, swelling, trachoma, ophthalmia. Stem: anti-inflammatory (Li 2003). Root: antimicrobial, cytotoxic. Stem: antioxidant Leaf: cytotoxic (Mosaddik 2004).

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Eucalypt woodland and freshwater stream. (Courtesy Craig Nieminski, flickr)

 The antimicrobial properties of the Australian Eucalypts are diverse and continue to be a subject of interest. (Volume 2 provides a substantial review of the subject.) Recent studies on Eucalyptus major (leaf, flower) and E. baileyana (leaf ) have shown excellent antibacterial potential, particularly against gram-positive bacteria – although they were devoid of antifungal properties. These studies of are of interest as they utilise methanolic plant extracts, rather than an essential oil. The latter is difficult to evaluate due to the insolubility of the oil in bacterial agar-gel studies and often a solubilising agent is utilised, which can give variable results. Methanolic extracts overcome this technical difficulty (Cock 2009b, 2008a).   Table 3.2 highlights the fact that Australian scientists are continuing to significantly expand their knowledge regarding the medicinal flora of this continent – an effort that is not widely acknowledged.

While we occasionally we hear of some new ‘breakthough’, most of us would little appreciate the decades of research that have usually accompanied such developments. Many reports have been filed away in scientific journals, and it can difficult to link chemical reports with practical clinical developments. The search has been further hampered by the fact that, until relatively recently, there has been little incentive for Australian companies to engage in expensive research efforts. This has slowly changed, although there are still quite serious problems with a burdensome bureaucracy that can be counterproductive and, in some cases, outright obstructive. Past initiatives in Australia have been compromised by a lack of governmental support, and there have been profitable enterprises such as the Duboisia alkaloids (see Chapter 9), that were taken over and developed by overseas concerns – while other ventures have faded into obscurity. It would be a great pity if this trend were to continue.

Chapter 4

NEW ROLES FOR OLD REMEDIES Australian native herbs have impressive healing attributes – although only a few have been exploited to their full potential. However, there are other traditions that indicate profound medicinal potential for some of these plants, or their close relatives, that have hitherto been largely ignored in this country. In many cases, the traditional use of numerous herbs has been verified by modern investigation, which serves to enhance their practical value. Some studies hint at greater healing attributes than is immediately apparent – as pharmacological evaluations of the Horsechestnut, Gotu Kola and Brahmi illustrate. Their benefits range from venous, tonic and woundhealing activity, to liver and kidney protective properties, as well as significant effects for memory enhancement. Gotu Kola is one of the herbal remedies with particularly interesting antimicrobial attributes that once led to its extensive use as an antileprotic remedy – a disease that many of us mistakenly consider a remnant problem, relegated to historical significance. The reality of the situation is quite different. The story of leprosy, an intractable disease with disastrous consequences for the sufferer, involves a rather amazing search for wound-healing remedies and a complex tale of antibiotic discovery. Even so, the role for herbal medicines, somewhat surprisingly, remains as valid today as in the past.

Gotu Kola.

and rockeries. It flourishes particularly well on damp swampy sites. The plant, which has also been known as Miner’s Lettuce, favours the east Australian coast, ranging from Victoria to tropical Queensland – as well as a being found in a few places in South Australia and southwest Western Australia. Despite its impressive medicinal potential, Centella asiatica is often considered to be little more than a tropical weed. The botanical literature, with regard to the classification of Centella and Hydrocotyle, can be somewhat confusing. Some authorities regard Hydrocotyle asiatica and H. cordifolia as synonyms for Centella asiatica – although others regard them as separate species. These plants are virtually indistinguishable in appearance. In addition, Gotu Kola has sometimes been erroneously known as Brahmi – a term ascribed to Bacopa monniera. It is a pity that many small herbs such

Centella: Ancient Remedy for the Modern World A Coastal Weed Gotu Kola or Indian Pennywort (Centella asiatica, formerly Hydrocotyle asiatica) is a slender creeping plant of garden edges, shady stone walls 137

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An early report in the Agricultural Gazette of New South Wales made mention of an indigenous plant possessing medicinal properties (Maiden 1894):

Gotu Kola as herbal lawn cover, no mowing required.

as Hydrocotyle and Centella are often seen as nuisance weeds. Surely some daisies, dandelions, oxalis, clovers and pennyworts could add an attractive diversity to the lawn environment, with the added benefit of a low growth habit and colourful flowers – although invasive imported weeds such as the Singapore Daisy (particularly in the rainforest environment) would be an exception. Certainly native species that can be utilised as natural lawn alternatives may be best left alone – rather than using expensive herbicides that poison the soil and add to chemical run-off in the urban setting. Gotu Kola or Indian Pennywort (Centella asiatica) is native to India, China, Indonesia, Australia, the South Pacific Islands, Madagascar and southern/central Africa. Throughout its range it has been regarded as a wound-healing herb par excellence. The fresh plant (or its juice) has been utilised in the treatment of a great diversity of wounds that range from abscesses and ulceration (chronic, scrofulous, or syphilitic with gummatous infiltration) to innumerable skin problems (psoriasis, chronic or obstinate eczema, boils, furunculosis, sweat rash). The entry for Centella asiatica in the 1868 Pharmacopoeia of India states: ‘In anaesthetic leprosy good results have followed the use of this herb, but it possesses no claim to the character of a specific attributed to it by some. It has been found more useful in secondary or constitutional syphilis, especially in those cases where the skin and subjacent cellular tissue are principally affected. In non-specific ulcerations, and in skin diseases, it is of value, both as an internal and as a local remedy.’

[Hydrocotyle] asiatica is found in moist places in many parts of the Colony. In the coast districts, and particularly near the northern rivers and table-lands where there is rich soil, it grows in the greatest profusion, covering the ground for large areas with a carpet of bright green … Mr. G. M. M’Keown, Manager of the Experimental Farm at Woollongbar, Richmond River, recently sent this plant to the Department, stating that it is ‘credited locally as valuable when applied to wounds or sores in the form of a salve or poultice’. This is the first occasion on which I have heard of it being put to use in New South Wales, but it is a well-known remedy in India, having been in use amongst the natives for many centuries.

Brisbane doctors accorded it similar esteem and the herb even gained some official recognition. In 1888 Gotu Kola was an exhibit at the Melbourne Centennial International Exhibition. The report in the Agricultural Gazette continued: The Pharmacographica Indica (1891) confirms the above estimate of the therapeutic value of the drug, and also states that it is so abundant in the Mauritius [Islands] that it serves as forage for cattle, whose milk it improves; it is also greedily eaten by pigs and other domestic animals. It is the more desirable to draw attention to an indigenous medicinal plant, as we have so few that, in the present state of our knowledge, possess undoubtedly valuable properties. In the bush it will be most convenient to employ the plant in the manner and for the uses indicated in Mr. M’Keown’s note.

  The Pennyworts Centella (Apiaceae) was formerly placed in the genus Hydrocotyle – which belongs to a different family classification, the Araliaceae. Over half the Hydrocotyle genus is found in Australia (41 of a total of 75). These fairly attractive creeping herbs of marshy and boggy places are often known as Pennyworts, and have a somewhat similar appearance to Gotu Kola. The Large-leaf Pennywort (Hydrocotyle bonariensis) is of interest as it is a medicinal herb that is widely distributed across the globe – from tropical and South Africa to the southern United

NEW ROLES FOR OLD REMEDIES

Hydrocotyle bonariensis. (Upper image courtesy Donald Hobern, flickr; lower image courtesy Franz Xaver, Wikimedia Commons, CC-by-SA 3.0 Unported)

States, Central and South America. In Australia it is found along the coastline from southern Queensland to Victoria, South Australia and Western Australia (southwest region). The plant has been utilised for treating inflammatory skin disorders including psoriasis, and as a cosmetic for freckles and skin spots. Extracts possess antifungal (fungicidal) activity against Candida krusei. This herb has also shown significant antiparasitic activity against Leishmania amazonensis (Tempone 2008).

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The Whorled Pennywort (Hydrocotyle verticillata) is a native species found throughout southeastern Australia, ranging to inland Queensland and South Australia, as well as southwest Western Australia – although it does not extend to the northern tropics or Tasmania. This species is often utilised as an aquarium foliage plant. (Image courtesy Kim and Forest Starr, Hawaii)

The Lawn Marsh Pennywort (Hydrocotyle sibthorpioides) is prolific throughout Victoria and Tasmania, extending along the coastline of New South Wales into southern Queensland. This native species has shown substantial immune modulatory and anticancer potential. The aquarium herb known as Brazilian Pennywort (Hydrocotyle leucocephala) is also of interest due to its immunosuppressive components (Huang 2008; Yu 2007; Ramos 2006). (Image courtesy Kim & Forest Starr, Hawaii)

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A Remarkable Therapeutic Repertoire Investigations of Centella asiatica and its components confirm significant wound-healing attributes. The Gotu Kola herb can directly promote collagen synthesis, which is important because collagen is a major skin component that is directly involved in the healing process. The effects are linked to its triterpene components – the most prominent of which are asiaticoside and madecassoside, and their sapogenins (asiatic acid and madecassic acid). In the past, particular emphasis has been placed on the cellular healing and antimicrobial effects of asiaticoside, although madecassoside appears to have equally impressive activity (Paolino 2012; Somboonwong 2012; Belcaro 2011; Hashim 2011; Maquart 1999; Sunilkumar 1998; Suguna 1996; Bonte 1995, 1994, Rush 1993). The effects of asiaticoside are multifaceted. It has substantial antioxidant and anti-inflammatory properties which facilitate the initial stages of healing.1 It can increase the vascularisation of connective tissue, provide support for the tensile integrity of the skin, and facilitate keratinisation (keratin is a protein primarily found in skin, nails, hair, tooth enamel), which is involved in skin formation – thereby also having a stimulant effect on hair and nail growth (Turton 1993; Shukla 1999a, 1999b). Importantly, not only does Gotu Kola promote skin repair, it also strengthens the cellular structure of the skin, maintaining its integrity. The use of the herb in the treatment of venous insufficiency, inflammation (phlebitis) and for ulceration of the extremities (e.g. leg ulcers) is not only based on a wound-healing effect – there is a supportive action on the venous circulation, with substantial antiinflammatory benefits. Bed sores and diabetic ulcers, which likewise involve impaired circulatory function, respond well to treatment with Gotu Kola. It can promote the formation of new epithelial cells and connective tissue, allowing the damaged tissue to be discarded more quickly. Therefore, burns heal quicker with its use, and it can reduce keloid (scar) formation (Somboonwong 2012; Kimura 2008; Liu 2008b; Altern Med Rev 2007). 1 The antioxidant activity of Centella asiatica (84%) has been found comparable to that of grape seed extract (83%) and vitamin C (88%) (Hashim 2011).

Gotu Kola extracts have anti-inflammatory, anti-pruritic (anti-itching) and anti-allergic properties (George 2009). Serious investigation of its use as a topical treatment for psoriasis has been suggested (Sampson 2001). The anti-inflammatory and antioxidant triterpenes asiaticoside and madecassoside make a significant contribution to its anti-psoriatic properties. Gotu Kola also has potential for use in cellulitis – a diffuse inflammatory disorder characterised by localised hot red patches of skin irritation (e.g. erysipelas) that can become extensive. The condition can be extremely painful and debilitating (Morganti 1999; Kartnig 1988). In addition, experiments tend to confirm an immunesupportive effect (Punturee 2005a, 2005b, 2004; Jayathirtha & Mishra 2004). The use of Centella in individuals with compromised immune system function, particularly where circulatory impairment can delay wound healing (such as diabetes), is certainly justified. A number of studies indicate Gotu Kola extracts can be useful following surgery. The herb has the ability to promote mucous membrane healing in ear, nose and throat surgery – for example, following tonsillectomy. It can enhance the healing process for all manner of surgical wounds (including episiotomy lacerations following childbirth) – as well as radiation-induced ulceration (Mowrey 1990). A cream combining Centella asiatica and Bulbine frutescens has been used clinically as a supportive healing agent following plastic surgery, specifically for the reduction of scar tissue formation. The cream not only promoted collagen production and facilitated wound healing, it had useful antibacterial and antiinflammatory activity (Widgerow 2000). Many products on the market that contain Gotu Kola are equally effective. Cream formulations combining Gotu Kola with ɑ-tocopherol and collagen-elastin hydrolysates can prevent the stretch marks of pregnancy – a combination that was found to be particularly useful for women who had developed them previously (Young & Jewell 2000). Gotu Kola may help prevent skin ageing and wrinkles. The herb has photoprotective properties and a cream prepared with madecassoside and vitamin C showed substantial benefits for chronic sun-damaged (photoaged) skin (Saraf 2012; Haftek 2008). Research continues to improve the bioavailability of Centella formulations

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A South African herb known as the Burn Jelly Plant (Bulbine frutescens) is well named. The fresh leaf yields a soothing mucilaginous juice with an excellent healing reputation that is particularly useful for burns – as well as all sorts of skin irritation (rashes, blisters, insect bites), cracked or fissured skin problems (lips, feet), acne, mouth ulcers and even cold sores (www.plantzafrica.com). (Image courtesy Stan Shebs, Wikimedia Commons, CC-by-SA 3.0 Unported)

Calendula officinalis. (Courtesy Fanghong, Wikimedia Commons Project, CC-by-SA 3.0 Unported)

on Calendula officinalis – instead it utilised a tincture of Marigold flowers from Tagetes patula with 10 per cent white paraffin. The results were very good: ‘After 3–4 weeks, patients using calendula ointment showed 30–40% reduction in depth and diameter of the trophic ulcers and absence of any secondary infection, despite their refusal to immobilize the affected part.2 Since calendula is a natural product with no known untoward effects we feel that our observations may be useful to field personnel facing similar problems’ (Kartikeyan 1990). Calendula officinalis does have a similar effective reputation (Jorge-Neto 1996).

Circulatory and Cardiovascular Support

Tagetes patula. (Courtesy Michael Lahanas, Scientific-web. com)

for more effective clinical use, including the development of titrated extracts of Centella asiatica (TECA), organogels and hydrogels (Belcaro 2011; Morales 2009; Hong 2005; Kim 2001). A number of other remedies with good woundhealing and antibacterial attributes have equally interesting potential. For instance, ‘Calendula ointment’ has shown practical benefits for treating trophic ulcers such as those of leprosy. However, Kartikeyan and colleagues (1990) provide an illustration where checking the botanical identification is essential. Despite the name, the preparation used in the investigation was not based

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Gotu Kola has an excellent reputation for diverse conditions involving impairment of the venous system, such as haemorrhoids and varicose veins (MacKay 2001). In the last decade, investigations have greatly expanded its therapeutic scope. The benefits of the herb have long been known to traditional Indian and Chinese medical practitioners, although European interest lagged behind until the advent of studies undertaken in Italy in the 1990s (Cesarone 1994, 1992). Subsequently, greater recognition of the significant benefits of the herb by the medical profession resulted from clinical studies undertaken at St Mary’s Hospital, Imperial College, London (Cesarone 2001a, 2001b, 2001e; De Sanctis 2001; Incandela 2001b, 2001c). 2 Immobilising the affected site was part of the treatment protocol as this helps to promote healing and prevent repeated trauma. Plaster casts, however, were considered stigmatising and not very practical as most patients needed to continue working. Antibiotics (neomycin) were the common method of ulcer treatment (Kartikeyan 1990).

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Gotu Kola Tincture. (Courtesy Nutrition Care)

Studies on the use of a triterpene fraction for treating chronic venous insufficiency demonstrated a favourable influence on the circulatory status of diabetic individuals – as well as being useful for the treatment of venous hypertension. Although the initial clinical studies were small, the results were impressive. Importantly, the extract helped to prevent the deterioration of peripheral circulation that can be a seriously debilitating long-term consequence of diabetes. The herb also has potential for improving cardiovascular function, notably for the treatment of atherosclerosis. It can stabilise plaque formation and thereby reduce the risk of thrombosis. The fact that the extract can be used in conjunction with other drug therapies, and is very well tolerated, is a substantial therapeutic bonus (Cesarone 2001d; Incandela 2001a, 2001d). The use of Gotu Kola for the prevention of thrombosis on long-distance travel is another point of interest. Clinically, use of a triterpene-rich extract showed a marked reduction in ankle swelling and oedema. There were practical benefits for individuals undertaking long-haul flights or road travel that could be particularly useful for preventing microcirculatory problems. Importantly, the extract was effective even when used on a short-term basis. The dose was fairly low – 60 mg three times daily for two days before, as well as during the flight, with its use being continued for the following day (Cesarone 2001c). Of course, for seriously compromised circulatory problems a more long-term strategy would be appropriate. However, a word of caution is required regarding the use of herbal therapies that influence the circulatory system. Although they can provide substantial benefits, their use with blood-thinning

drugs such as warfarin (the use of which can be a complicated undertaking at the best of times) requires careful monitoring. Even so, this does not preclude the use of supportive herbal therapies.   Centella’s therapeutic potential appears to be best evaluated according to its chemical characteristics, with an emphasis on asiaticoside and madecassoside as the compounds of primary interest. This has been made somewhat easier with the development of a number of standardised triterpenoid-rich extracts (James & Dubery 2009): • TECA (titrated extract): composed of asiatic acid (30%), madecassic acid (30%), asiaticosides3 (40%) •  TTF (total triterpenoid fraction): composed of asiatic acid and madecassic acid (60%), asiaticosides (40%). • Madecassol extract: asiaticoside (40%), asiatic acid (29–30%), madasiatic acid (1%). There is another aspect of Gotu Kola’s chemical complexity that is worthy of note. The main components of the terpenoid-rich essential oil are: ɑ-humulene, β-caryophyllene, bicyclogermacrene, germacrene, myrcene, trans-β-farnesene, and p-cymol4 (James & Dubery 2009). Certainly, some of these would exert an influence on the activity of the herb. In addition, various other components are present in plant extracts: an alkaloid (hydrocotylin), flavonoids (kaempferol, quercetin, rutin) and other phenolic compounds (catechin), sterols (stigmasterol, sitosterol), amino acids, resin and a bitter principle (vellarine).   The herb’s use as a vegetable is certainly supported by its nutritional value: vitamins (vitamins B, C, carotenoids) and minerals (calcium, magnesium, phosphate, sulphate, sodium, potassium, chloride). Indeed, iron levels can be quite high (12 mg/100 g). There is also a reasonable calcium (176 mg/100 g) and carotene (2400 mcg/100 g) content (Jamil 2007). The carotenoids of interest include β-carotene (255 μg/g dry weight), lutein (980 μg), neoxanthin (103 μg) and violaxanthin 9255 μg) (Chandrika 2010).

3 There is more than one form of asiaticoside. In addition to the original compound, asiaticosides B, C, D, E and F have been identified. 4 Other studies have shown variations in the main components. A volatile oil with antidepressant activity contained farnesol, elemene and caryophyllene. Another analysis showed ɑ-humulene, β-caryophyllene and bicyclogermacrene predominated (Zheng & Qin 2007).

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  A Complex Triterpenoid Chemistry Centella asiatica.

There appears to be quite a deal of variability in the constituents of Gotu Kola plants obtained from different sources. The herb can contain a number of components that are very similar chemically. However, the older literature is confusing, with duplicate chemical names, synonyms and, at times, contradictory findings marring the clarity of the picture (James & Dubery 2009). For instance, one study stated brahmic acid was identical with madecassic acid, while isobrahmic acid was a mixture of asiatic and madecassic acids (Kartnig 1988). Yet another report stated isobrahmic acid was identical to madecassic acid (an isomer of terminolic acid). Currently brahmic acid and madecassic acid are considered to be the same (6-β-hydroxy-asiatic acid) (James & Dubery 2009). For a long time Madagascar-sourced Centella asiatica was justifiably considered preferable as a wound-healing remedy due to its higher asiaticoside content. This was a fairly safe option, particularly as diverse studies reported considerable variability in plant extracts from other sources – a chemical complexity that would be, for most of us, quite bewildering. There are, however, varieties that maintain a great deal of similarity and the discovery of different chemical races of the herb has helped to clarify the situation (Kartnig 1988). The total triterpenoid content was, in general, found to be comparable between plants from India, Korea and Madagascar – although

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differences occurred in the ratio of free acids (e.g. asiatic acid) to glycosides (e.g. asiaticoside). Rosmarinic, betulinic and ursolic acids are additional compounds of pharmacological interest. Some species also contain saponins (e.g. centellasaponins A, B, C, D). The standard reference is: asiaticoside (1 mg/ ml), madecassoside (3 mg/ml) and asiatic acid (10 mg/ml) (Zainol 2008). Overall the following characterises plants obtained from different locations (James & Dubery 20095): •  Madagascar: asiaticoside, asiatic acid, madecassoside and madecassic acid. Asiaticoside is present at high levels (2.6– 6.42% dry weight) in the leaf. The roots contain negligible levels. Cultivated plants had a much lower saponin content (asiaticoside 0.7–0.9%, madecassoside 1.1–1.6% dry weight). •  South Africa: asiaticoside, asiatic acid, madecassoside and madecassic acid. •  Sri Lanka: centelloside, centellic acid (plus centic and centoic acids). •  Indian-sourced plants showed the greatest chemical variability (with different chemical types as listed): asiaticoside, asiatic acid, madecassoside and madecassic acid (plus brahmic acid) asiaticoside and asiatic acid  brahmoside and brahmic acid (plus isobrahmic acid)  brahminoside, brahmic acid (plus betulinic acid) thankuniside, thankunic acid (plus asiatic acid) isothakuniside and isothankunic acid (plus asiatic acid) • Malaysian samples (mg/ml) were found to be low in asiatic and madecassic acids (0.55 ± 4.58 mg; 0.55 ± 0.89 mg, respectively), although the level of madecassoside (3.1 ± 4.58 mg) and asiaticoside (1.97 ± 2.65mg) were good (Hashim 2011). 5 A complete list of triterpenes and their chemical structures is available in James & Dubery (2009). Ursolic and betulinic acids are discussed in greater detail in Volume 2 under Triterpene discoveries.

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•  Southern Malaysian samples (mg/ml): asiaticoside (2.5 mg), madecassoside (5.3 mg), asiatic acid (3.4 mg) (Zainol 2003). Other leaf samples6 have shown substantial variability (mcg/ml): asiaticoside (0.39– 2.56 mcg), madecassoside (0.71–5.3 mcg), asiatic acid (undetectable–1142.67 mcg). Substantial levels of asiatic acid (2390 mcg) were also present in the petioles. • Australian sources have similar potential for chemical variability. It is also possible that the native herb is not entirely botanically identical with overseas samples and may even be a different variety or sub-variety. At one time the native plant was assigned a separate species name, Centella cordifolia. 6 While root samples normally contain minimal amounts (if any) of these triterpenes, in this study levels of 3421 mcg/ml asiatic acid and 1.57 mcg/ml madecassoside were present.

A Neuroprotective Agent

Gotu Kola has been traditionally valued as a brain tonic and memory-protective herb – a reputation that has been supported by current research. The herb has antioxidant, anti-inflammatory and neuroprotective properties that affect brain function, with potential benefits for age-related memory loss and conditions such as Alzheimer’s and Parkinson’s diseases. It may even be useful for neurodegenerative disorders such as Huntington’s disease and multiple sclerosis. The research effort regarding this area of the plant’s potential has been impressive. Interestingly, some experiments have indicated that Gotu Kola can help the regeneration of nerve cells. Moreover, the herb has shown anti-epileptic (anti-convulsant) and antidepressive potential that suggest its use as an adjunct for the treatment of epilepsy and mood disorders (Orthan 2012; Xu 2012; Kumar 2011; Haleagrahara & Ponnusamy 2010; Visweswari 2010; Dhanasekaran 2009; Barbosa 2008; Gadahad 2008; Wattanathorn 2008; Xu 2008; Mohandas Rao 2007; Mukherjee 2007; Ramanathan 2007; Chen 2005; Rao 2005; Soumyanath 2005; Subathra 2005; Vattanajun 2005; Chen 2003; Gupta 2003; Veerendra Kumar & Gupta 2003, 2002).

Rosmarinic Acid

Rosemary (Rosmarinus officinalis) herb contains a number of components with anticancer properties, notably rosmarinic acid, carnosol, carnosic acid and ursolic acid (Ngo 2011).

Rosmarinic acid, which is a caffeic acid derivative, has been identified as a primary active component of Centella asiatica extracts showing anticancer (antiproliferative) activity – although other components contribute to this effect, including various triterpenes (ursolic, pomolic, asiatic and corosolic acids, etc.) (Yoshida 2005). Importantly, recent research has suggested that rosmarinic acid has a cognition-enhancing effect that indicates it could be useful for memory disorders (e.g. Alzheimer’s disease) – as well as neurodegenerative problems such as amyotrophic lateral sclerosis (Wang 2012; Bulgakov 2011). Rosmarinic acid has important pharmacological properties and rates among the most notable of the phenolic chemicals. It is prevalent in numerous aromatic Lamiaceae herbs (subfamily Nepetoideae), such as lemon balm, rosemary, sage, thyme, oregano and peppermint. This compound, which is also widespread in the Boraginaceae family, is of interest due to its antioxidant, anti-inflammatory, antiviral and antibacterial attributes. It has the potential to influence diverse inflammatory and spasmodic conditions such as asthma, intestinal disorders and allergies. Rosmarinic acid has been investigated for treating peptic ulcers, atherosclerosis, liver fibrosis, ischaemic heart disease, cataract and retinal disorders, rheumatoid arthritis and infertility (poor sperm motility) (Bulgakov 2011; Petersen & Simmonds 2003). Rosmarinic acid has also shown potent antiviral activity against Japanese encephalitis virus (Swarup 2007).

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The cancer chemopreventive effect of rosmarinic acid may well impart a dietary anticancer property to the culinary use of herbs such as Rosemary and Thyme. The compound may also have valuable potential for reducing the side-effects of chemotherapy, and skinprotective effects (against UV light damage). In particular, it has been suggested that rosmarinic acid has a preventive effect against colon carcinogenesis (Karmokar 2012; Sharmila & Manoharan 2012; Bulgakov 2011). Surprisingly, some studies have found that Mints, notably Mentha spicata, generally contain a higher content (mg/g) of rosmarinic acid (19–58 mg) than Rosemary herb (7–10 mg). The level, however, can vary considerably according to the species or variety analysed. Other studies have found moderate amounts (10 mg) in Sage and Spearmint, with low levels in Lavender and Thyme (around 2 and 6.6 mg, respectively). Melissa officinalis was another good resource (36–39 mg) – although climatic and soil conditions have a significant influence on yield quality (Shekarchi 2012).

Thirteen species of Mint are found in Australia. Mentha spicata is particularly widespread, being naturalised throughout the entire continent and Tasmania. (Upper image courtesy jacilluch, flickr; lower image courtesy Charissa Lansing, flickr)

Melissa officinalis, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

Lemon Balm (Melissa officinalis) can be found naturalised from South Australia to Victoria, New South Wales and Tasmania. This herb and the essential oil have good antiviral remedy against the Herpes simplex virus with potential for clinical use (Astani 2012; Mazzanti 2008; Schnitzler 2008; Dimitrova 1993; Cohen 1964). Other familiar aromatics (oils and extracts) with similar anti-Herpes potential include Peppermint (Mentha x piperita), Sage (Salvia officinalis), Rosemary, Thyme (Thymus vulgaris) and Prunella (Prunella vulgaris) (Geuenich 2008; Nolkemper 2006; Schuhmacher 2003).

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Two rosmarinic acid derivatives are also of pharmacological importance: lithospermic acid B (salvanolic acid B) and rabdosiin. These compounds have anti-inflammatory, antioxidant and kidneyprotective properties. In particular, lithospermic acid showed significant experimental effects against diabetic nephropathy (as did rabdosiin), anticancer activity in head and neck squamous cell carcinoma, microcirculatory protection with potential in cerebrovascular and cardiac conditions, and additional cardioprotective (antiatherosclerosis) properties. Rabdosiin also had anti-HIV potential. Salvia miltiorrhiza and Lithospermum erythrorhizon are good sources of lithospermic acid B, with the latter also yielding rabdosiin (see Bulgakov 2011 for details).

Salvia miltiorrhiza (Chinese Sage) dried root. This herb, known as Dan Shen, is traditionally utilised for treating gynaecological disorders and as a cardiotonic. It is highly respected in Chinese medicine.

Gotu Kola is a rather remarkable small weed which even appears to have detoxicant attributes that support its reputation as a blood-purification agent. Investigations of the effects of the herb in arsenic toxicity showed that Gotu Kola had a significant antioxidant effect that reduced cellular damage and provided substantial support for liver function. It also had protective benefits for the kidney and brain – although it was not a chelation agent (Huda-Faujan 2007; Flora & Gupta 2007; Gupta & Flora 2006). This level of protection, which was associated with bioflavonoid components, has potential for reducing the mental effects of lead exposure in children when used in combination with a chelating compound (Ponnusamy 2008; Saxena & Flora 2006). This provides interesting support for its traditional use in China as an antidote to poisoning from wild mushrooms and Gelsemium elegans (Chang 1989). There is, however, a matter of individual sensitivity to the plant. While Gotu Kola appears to be well tolerated in most people, there are some unfortunate individuals who suffer contact dermatitis on exposure to the herb (or asiaticoside). There has also been a report of photosensitisation associated with its use (Gonzalo Garijo 1996; Bilbao 1995; Chopra 1958). While Gotu Kola has rarely been involved in reports of side-effects, it is possible that heavy metal contamination can occur (Tripathi 2012), and that individual sensitivities may involve other forms of allergic reaction. There are also a few reports of hepatotoxic reactions linked to Gotu Kola, but these do not make a lot of sense considering the strong antioxidant, anti-inflammatory and hepatoprotective properties of the herb. It is more likely this could be associated with some form of toxin contamination, herbal substitution or incorrect identification of the plant used for the raw material. For instance, various species of Germander (Teucrium spp.) have definitely been linked to hepatotoxicity.

  Toxic Jessamine

Lithospermum erythrorhizon (Red Root Gromwell), Zi Cao, is primarily recommended for treating febrile and inflammatory disorders including skin eruptions, measles and burn injuries.

Gotu Kola has traditionally been utilised as a detoxicant remedy for Gelsemium poisoning. There are three species in the Gelsemium genus. All are toxic as they contain strychnine-related alkaloids (gelsemine, gelseminine) and cause a form of poisoning that has been compared to Hemlock toxicity (loss of consciousness, paralysis and death). The nectar, which will even poison

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as a criminal poison. Indeed, in December 2011 the Chinese billionaire Long Liyuan is said to have been poisoned with the drug, which was allegedly put in a cat-meat stew (BBC News Asia, 4 January 2012).

The decorative American Yellow Jessamine (Gelsemium sempervirens) is one of the toxic ornamental plants that can be found in temperate Australian gardens (New South Wales, Victoria). This vine is the basis of the well-known homoeopathic medicine Gelsemium, which has been utilised for neurological problems. (Image source: Ellis Rowan painting, from Alice Lounsberry, Southern Wild Flowers and Trees, Frederick A. Stokes Company, New York, 1901)

bees, has been linked to incidents of poisoning of children who sucked the blossoms.   The depressant effect of the alkaloids once saw the herb used as a nervous system depressant with sedative, analgesic and antispasmodic properties. This also led to its popular use as an asthmatic and whooping cough remedy, albeit the risk of fatalities was high (Dobelis 1986). It was also recommended for the treatment of trigeminal neuralgia and migraine (BHP 1983) – although the homoeopathic preparation would be a much safer alternative. Gelsemium elegans, which is known as Heartbreak Grass, is from Southeast Asia and China, and has an equally toxic reputation that even led to its use

In Chinese medicine, the use of Gotu Kola (Centella asiatica) extended far beyond the European recommendations for treating wounds and skin diseases – being utilised for diverse disorders affecting the gastrointestinal, urinary and respiratory tracts. The fresh juice has been taken for uraemia, urinary problems (whitish, muddy urine), throat inflammation, and conditions characterised by agitation, chronic thirst, diarrhoea and vomiting – which is suggestive of conditions such as enteritis due to food poisoning. The decocted herb with lean pork was recommended for whooping cough, or a tea taken for measles. In infectious hepatitis the herb was decocted, sugar added, and the mixture taken twice daily for a week. An infusion prepared from the powdered herb has also been taken for pleurisy, and to ease the aches and pains associated with old wounds (Chang 1989).

Table 4.1 Summary of Recent Investigations of Centella asiatica

The table overleaf provides an indication of the remarkable amount of interest that has been expressed in Gotu Kola. This extensive range of investigations attest to the importance of Centella asiatica as a medicinal plant – confirming many of its traditional uses, as well as suggesting new avenues of therapeutic value.

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Table 4.1 Summary of Recent Investigations of Centella asiatica Medicinal properties Wound-healing studies

Antimicrobial properties

Cardiovascular and cerebrovascular

Liver (hepatoprotective)

Respiratory tract Antidiabetic potential

Radiation (radioprotective) properties

Investigations (author) Numerous studies have investigated the efficacy of Gotu Kola, asiatic acid and madecassoside as wound-healing agents (Ermertcan 2008; Kimura 2008; Liu 2008; Shetty 2006; Wollina 2006; Hong 2005; Lu 2004a, 2004b; Biswas & Mukherjee 2003; Coldren 2003; MacKay & Miller 2003; Brinkhaus 2000; Widgerow 2000; Maquart 1999; Shukla 1999a, 1999b; Sunilkumar & Shivakumar 1998; Suguna 1996). Promotion of wound healing in cases of diabetic ulcer (Paocharoen 2010). Scar management: strong wound-healing attributes for asiaticoside; can reduce scar formation (Tang 2011); clinical use of Gotu Kola for scar management and stretch marks of pregnancy (Young & Jewell 2000; Widgerow 2000). Cosmetic: extracts have been widely incorporated into creams etc. for an ability to stimulate collagen, aiming to restore skin firmness, elasticity and improve skin appearance. Extracts have also shown a mild UV protective effect (Hashim 2011). Centella asiatica extract has a very broad spectrum of antimicrobial activity. It has demonstrated antibacterial activity against Staphylococcus aureus, as well as antibioticresistant strains (MRSA: methicillin-resistant S. aureus) (Zaidan 2005). Extracts have activity against diverse gram-positive bacteria (Bacillus cereus, B. megaterium, B. subtilis, Sarcina lutea) , gram-negative bacteria (Aeromonas hydrophila, Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphi, S. typhi, S. typhimurium, Shigella boydii, Sh. flexnerii, Sh. dysenteriae, Vibrio cholerae, V. mimicus, V. parahaemolyticus) and anti-fungal activity (Candida albicans, Aspergillus niger, Saccharomyces cerevaceae) (Ullah 2009; Mamtha 2004). Antiviral potential (Zheng 1989): acts as an antiviral attachment agent against pseudorabies virus (Hosni 2006). Anti-herpes virus activity. An additive effect was seen with Mango (Mangifera indica) extracts; active components were asiaticoside and mangiferin, respectively (Yoosook 2000). Dental: use of extracts of Gotu Kola and Pomegranate (Punica granatum) significantly improved clinical signs of chronic periodontitis (Sastravaha 2005, 2003). Asiaticoside has shown particularly good effects for enhancing periodontal healing (Nowwarote 2012). Studies that have indicated the protective properties of Gotu Kola may extend to ischemia and reduction of arterial plaque. This provides support for the use of the herb as a heart tonic and for conditions such as heart attack or stroke. Madecassoside has been identified as a primary active component (Cao 2010; Bian 2008; Li 2007b; Pragada 2004; Cesarone 2001d). Gotu Kola contains cardiac glycosides that may contribute to a cardiotonic effect of the herb (Krishnaiah 2009). Gotu Kola extracts have shown cellular protective effects on the heart with potential for use in preventing the toxic side-effects of some drugs, e.g. the cardiovascular toxicity associated with the antibiotic adriamycin (doxorubicin) that is used in cancer chemotherapy (Gnanapragasam 2007, 2004). Gotu Kola contains a caffeoylquinic acid with anti-thrombotic activity (Satake 2007). Centella asiatica has shown potential for the treatment of cirrhosis and fibrosis, including bilharziainduced liver fibrosis due to the schistosomiasis parasite. Chinese investigations of asiaticoside have shown a remarkable hepatoprotective effect on chemical-induced liver injury (Zhang 2010b; Ming 2004; Kartnig 1988). Chronic hepatitis did not respond to its use (Kartnig 1988). Asiaticoside has shown experimental protective effects against septic lung injury (Zhang 2011c, 2008). Extracts have shown good potential for blood sugar regulation (Babish 2010; Krishnaiah 2009). The circulatory benefits of Gotu Kola extend to improvement of peripheral circulation in diabetic individuals (Cesaronbe 2001b, 1994). Used to promote wound healing in diabetic individuals (Paocharoen 2010). Gotu Kola has shown significant antioxidant and radioprotective potential. It acts to protect against cellular damage and normalise cellular function in radiation injuries (Joy & Nair 2009; Jayashree 2003; Sharma & Sharma 2005, 2002). Gotu Kola extracts may be valuable for treating radiation treatment side-effects involving taste perception and weight loss (Shobi & Geol 2001). An evaluation of madecassol (asiaticoside) and tetrandrine on skin radiation injuries demonstrated that both products were able to reduce acute radiation reactions due to a significant anti-inflammatory activity. Tetrandrine, a compound isolated from Stephania tetrandra and some other Stephania species, was particularly effective (Chen 1999). Note: Although S. tetrandra is not found in Australia, there are four native species of Stephania.

NEW ROLES FOR OLD REMEDIES Anticancer (anti-tumour and cytotoxicity studies)

Gastrointestinal disorders

Anti-inflammatory and antiarthritic properties

Neuroprotective (nerve protective) and mood disorders

Detoxicant (chemotoxin and heavy metal protection)

Antiparasitic and insecticidal potential

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The traditional use of Gotu Kola as an anticancer remedy has received experimental support. Extracts have shown cytotoxic and anti-tumour activity in animal studies (Babu 1995). Gotu Kola extracts: experimental anticancer activity in mouse melanoma, human breast cancer and rat glioma cell lines. Flavonoids showed antioxidant and antitumor activity (Pittella 2009). Gotu Kola extracts: apoptosis-inducing effect on breast cancer cells (Babykutty 2008), and in colon cancer studies (Bunpo 2004). Asiatic acid: induced apoptosis in numerous cancer cell lines including colon cancer (Tang 2009), and human melanoma cell lines (skin cancer treatment potential) (Park 2005). Asiaticoside: apoptosis-inducing effect; enhanced the anti-tumour activity of vincristine in cancer cells, which suggests it may be a useful adjunct in cancer chemotherapy (Huang 2004). Centella asiatica extract has shown protective activity against genotoxic agents (cyproterone acetate) (Siddique 2008). Immunomodulating and anti-inflammatory properties with chemopreventive or anticancer potential (Punteree 2005, 2004). Gotu Kola can strengthen the mucosal barrier of the gastrointestinal tract, promoting healing in gastric and duodenal ulcers and protecting against chemical injury, e.g. from aspirin or ethanol (Abdullah 2010; Guo 2004; Cheng 2004; Sairam 2001a; Cheng & Koo 2000). The herb also contains a compound (3,5-dicaffeoyl-4-malonylquinic acid) with potential for use in inflammatory bowel disease (di Paola 2010). The herb has long had a reputation as an arthritis cure. A few fresh leaves are eaten daily or it can be air-dried, powdered, and stored for later use. Studies have supported the anti-arthritic activity of Gotu Kola and suggested potential cartilage protective activity that could be useful for osteoarthritic problems. Madecassoside was identified as a significant anti-rheumatic, anti-arthritic, anti-inflammatory and cartilage protective component of extracts (Hartog 2009; Li 2009; Liu 2008a; Li 2007a). Madecassic acid has shown a more potent suppressive effect on some inflammatory mediators than madecassoside (Won 2010). Madecassol (a proprietary preparation) has had some success in the treatment of scleroderma (a chronic systemic autoimmune disease): improving joint pain (arthralgia), mobility of the fingers, and decreased skin indurations (Mowrey 1990, Kartnig 1988). Centella asiatica extracts: significant antinociceptive (analgesic) activity comparable to aspirin (but weaker than morphine), and anti-inflammatory activity comparable to mefenamic acid, a NSAID that is also used for menstrual pain (Somchit 2004); asiatic acid demonstrated analgesic and antiinflammatory activity (Huang 2011). Gotu Kola: protective effects on brain function including neurodegenerative diseases, protection for ageing process and enhancement of learning and memory (Haleagrahara & Ponnusamy 2010; Dhanasekaran 2009; Kumar 2009; Barbosa 2008; Wattanathorn 2008; Xu 2008; Mukherjee 2007; Rao 2005; Subathra 2005; Gupta 2003; Veerendra Kumar & Gupta 2003, 2002). Nerve regeneration prospects (Mohandas Rao 2007, 2006; Gadahad 2008; Soumyanath 2005). Epilepsy (Visweswari 2010; Vattanajun 2005). Anti-anxiety and anti-depressive activity (Wanasuntronwong 2012; Jana 2010; Chen 2005; Chen 2003). Asiatic acid has shown anti-ischaemic neuroprotective properties in the brain, with potential for use in rehabilitation of stroke patients (Tabassum 2012; Krishnamurthy 2009). Gotu Kola and asiaticoside-derivatives deserve serious consideration for use as neurotoxinprotective agents (Shinomol 2010; Shinomol & Muralidhara 2008a, 2008b; Ramanathan 2007; Jew 2000; Lee 2000; Mook-Jung 1999). Asiaticoside: neurotoxin protection in studies of Parkinson’s disease (Xu 2012). Gotu Kola can provide cellular protection against lead and arsenic toxicity (Sainath 2011; Ponnusamy 2008; Saxena & Flora 2006; Flora & Gupta 2007; Gupta & Flora 2006). It is, however, not a chelation agent. This hyperaccumulation effect, though, is not without risk if the plants are wild harvested from sites high in arsenic or lead (Tripathi 2012). Antiprotozoal activity against Entamoeba histolytica (Jamil 2007). Antifilarial effect: when combined with Acacia auriculiformis against Dirofilaria immitis in dogs (Jamil 2007). Intestinal helminth infections: moderate anticestodal activity against Raillietina echinobothrida (Temjenmongla & Yadav 2005). Leaf extracts showed activity against sheep fluke (Paramphistomum cervi) and larvae of malaria mosquito vector (Anopheles subpictus) (Bagavan 2009). Larvicidal and mosquitocidal activities against larvae and adults of Anopheles stephensi. Combination of Blue Gum (Eucalyptus globulus) and Gotu Kola had a synergistic effect (Senthilkumar 2009). Gotu Kola essential oil, however, showed only a mild degree of mosquito-repellent activity. The main constituents of the oil were farnesene, caryophyllene and p-cymol (Rajkumar & Jebanesan 2007).

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Remedies for Recollection

Bacopa is a small creeping, succulent herb with a fairly nondescript appearance. Native to the tropics, it is usually found on swampy lands. Australian species of Bacopa (family Plantaginaceae) include B. floribunda, B. monnieri and B. procumbens, while B. amplexicaulis is an introduction. Their preference for wet marsh-like environments is signified by the English names Water Hyssop and Thyme-leaved Brooklime. These herbs may well provide some interesting environmental benefits. Bacopa monnieri has shown arsenic chelation properties. The herb is also very cadmium tolerant, making it a good candidate for phytoremediation projects (Mishra 2011, 2006; Singh 2006). (Images courtesy Kim & Forest Starr, Hawaii)

Bacopa monnieri (syns Herpestris monniera, Brahmia indica), or Brahmi, is one of the impressive herbs of Indian therapeutic traditions that is also native to Australia. This ancient and highly valued medicinal plant was mentioned in Hindu Vedas that date back to around 5000 BC. Brahmi has been used in Ayurvedic medicine since about 500 AD for improving memory and concentration. However, there is some contention over the true identity of the herb in the ancient literature – and, while it appears Centella asiatica was also known as Brahmi in some places, it is more correctly known as Mandukaparni (Kakkar 1988; Wohlmuth 2000). Traditionally Bacopa monnieri is a highly regarded nervous system restorative that has been recommended for cases of hysteria, epilepsy, insanity and neurasthenia (nervous debility). It has a valuable tonic (adaptogenic) effect that was said to enhance vitality and promote longevity. Ayurvedic medicine also considers that Brahmi possesses diuretic, liver tonic, anti-dyspeptic and cleansing properties – hence its deployment as a blood purification herb for removing ‘poisonous affections’ and for dermatological disorders. These traditional recommendations are supported by numerous investigations. Anti-fatigue, anti-anxiety, sedative, cardiotonic, anti-ischaemic and vasoactive properties are associated with the herb’s antioxidant, cardiac, tonic and nervine effects (Anand 2011; Kamkaew 2011; Chatterjee 2010; Mohanty 2010; Kapoor 2009; Sheikh 2007; Rai 2003; Wohlmuth 2000; Kapoor 1990). Other studies have confirmed Brahmi’s antiinflammatory, anti-arthritic and wound-healing properties. The herb has good antifungal activity, as well as antibacterial activity against Escherichia coli. Brahmi contains a number of pharmacologically active components, including bacosides, bacosaponins and sterols (β-sitosterol, stigmasterol). Betulinic acid (a triterpene) is also present – which is known to be a potent antioxidant, anti-inflammatory and antibacterial agent (Viji & Helwn 2011; Sharath 2010; Vijayan 2010; Viji 2010a, 2010b; Channa 2006; Ravikumar 2005; Chaudhuri 2004). Recent investigations suggest that a triterpene component, bacosine, has a blood sugar-reducing (antihyperglycaemic) and antioxidant effect that could be of benefit in diabetes (Ghosh 2011). Investigations also indicate an effective antiulcer (mucus-protective) action in chemical and

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stress-induced gastric ulceration. Studies have found that extracts had an anti-Helicobacter pylori effect that would contribute towards the herb’s efficacy (Goel 2003; Dorababu 2004; Sairam 2001b). The antispasmodic properties of Brahmi extract would also suggest that it could be useful for the treatment of irritable bowel disorders, although this remains unresolved (Altern Med Rev 2004; Yadav 1989). Brahmi has been traditionally used for treating fevers and respiratory disorders, including bronchitis and asthma. It was poulticed and applied locally to the chest for bronchitis and to ease coughing, particularly in children. Brahmi extracts have demonstrated substantial spasmolytic (antispasmodic) and bronchovasodilatory properties. The use of the herb in allergy and some forms of asthma is further supported by antihistamine properties comparable to disodium cromoglycate (Intal), a conventional anti-allergy and asthma medication. Investigations showing antiinflammatory, relaxant and immune tonic properties provide additional support for its use (Yamada 2011; Saraphanchotiwitthaya 2008; Channa 2003; Samiulla 2001; Dar & Channa 1999, 1997). In addition, Brahmi extracts have substantial hepatoprotective activity. There is a suggestion that its liver and kidney protective effects may be useful against drug-induced damage, including that associated with morphine use. It may also have the ability to enhance the analgesic effects of morphine, reducing the level of opiate drug tolerance (Bhaskar & Jagtap 2011; Rauf 2011; Menon 2010; Janani 2009; Sumathi & Niranjali Devaraj 2009; Sumathi & Nongbri 2008; Sumathi 2002; Sumathy 2001). Furthermore, the herb has shown experimental anticancer activity – with the hepatoprotective antioxidant component, bacoside A, having cancer chemopreventive effects on liver function. Triterpene saponins (bacopasides) are also of interest as antitumour components of the herb (Janani 2010, 2009; Peng 2010; Rohini & Devi 2008). The most extensive body of research on Brahmi’s therapeutic properties has involved its use as a nervine tonic, memory-enhancement and neuroprotective agent. It has significant antioxidant, anxiolytic and cognition-enhancing effects that benefit brain function. Triterpene saponins and their bacosides are the main compounds that enhance nerve impulse transmission (via repair of neuronal damage), which facilitates memory recall and retention (Vollala 2011a,

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2011b, 2011c; Altern Med Rev 2004). Clinical trials not only support its effect on memory, as improvement in related conditions can also be expected: work-related mental fatigue, epilepsy (reducing the incidence of fitting), insomnia, headache, depression, palpitations and irritability. Mental capacity in children with brain function problems and attention-deficit disorder has responded particularly well to the use of Brahmi (Morgan & Stevens 2010; Calabrese 2008; Raghav 2006; Sairam 2002; Bhattacharya 2000; Lodha & Bagga 2000; Negi 2000; Wohlmuth 2000; Kidd 1999, Tripathi 1996). The herb is more appropriate for long-term use than for short-term treatment, and supplementation for at least three months is usually recommended (Wohlmuth 2001; Stough 2001). Interestingly, Brahmi’s brain neuroprotective and antioxidant properties can extend to incidents of stroke, pesticide or aluminium poisoning, Parkinson’s and Alzheimer’s diseases (Jadiya 2011; Saraf 2011, 2010a; Shinomol & Muralidhara 2011; Singh 2011, 2010; Tripathi 2011; Hosamani & Muralidhara 2010; Uabundit 2010; Hota 2008; Limpeanchob 2008; Stough 2008; Dhanasekaran 2007; Jyoti 2007; Rehni 2007). It may also be useful as an antioxidant neuroprotectant against cellular damage due to cigarette smoke, particularly in the brain (Vijayan & Helen 2007; Anbarasi 2006a, 2006b, 2005a, 2005b, 2005c). Mentat is a combination herbal formulation that has shown some remarkable effects for mental function, particularly in children. This complex preparation contains a number of different herbs recommended in Indian traditions as adaptogens and for improving brain function. In addition to Gotu Kola and Brahmi the primary components are: Ashwaganda (Withania somnifera), Evolvulus alsinoides, Jatamansi (Nardostachys jatamansi), Amla (Emblica officinalis), Guduchi (Tinospora cordifolia), Sweet Flag (Acorus calamus) and Triphala.7 Additional herbal constituents include Ipomoea digitata, Asparagus (Asparagus racemosus) and Valerian (Valeriana wallichii). Mentat and similar formulations have demonstrated definite memory-protective and anxiety-reducing properties – as well as anti-amnesic effects (Anand 2010; Saraf 2010b; Prabhakar 2008; Vinekar 1998; Faruqi 1995; Andrade 1994, 1995; Joseph 1994; Bhardway & Srivastava 1995; Bhattacharya 1994). 7 Triphala is a combination herbal product that is composed of Chebulic Myrobalans (Terminalia chebula), Emblic Myrobalans (Emblica officinalis) and Belleric Myrobalans (Terminalia belerica) (Kapoor 1990). See also Volume 2.

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A number of clinical studies have given promising results with the use of Mentat in both hyperactive and mentally disabled children – reducing agitation, increasing the attention span, improving communication skills and scholastic performances. Associated disorders such as nocturnal enuresis (bedwetting), pica (unusual or abnormal cravings) and breath-holding spells improved significantly. There was also mild improvement in school phobia, learning disabilities and speech defects (Dave 1993; Kulkarni & Verma 1992; Koti 1991; Master & Rajguru 1991; Paranjpe 1991; Indira Bai & Sastry 1991; Seth 1991; Shah 1992, 1991; Verma & Kulkarni 1991).

Clinically, Mentat can favourably influence problems such as emotional expression, work performance, speech responses and relationship skills in schizophrenic patients (Shah 1991). The remedy has been found useful for reducing seizures in epileptic patients.8 In the treatment of mentally disabled children with epilepsy Mentat had significant benefits for controlling abnormal behaviour (hyperactivity and incongruous behaviour). It was used in addition to established antipsychotic and antiepileptic drugs. The protective action of Bacopa monnieri against drug-induced side-effects would suggest this herb has additional benefits. One study on the concurrent use of carbamazepine and phenytoin (anti-epileptic medication) with Mentat demonstrated an increased bioavailability of these drugs – which would permit the use of lower doses (Tripathi 2000; Vohora 2000; Kulkarni & George 1995; Moharana 1994; Dave 1993). The ability of Mentat to stabilise emotional responses and mental functioning has led to investigations of its use in drug withdrawal states. Alcohol withdrawal is characterised by nervous system dysfunction such as tremors, hallucinations and convulsions, as well as delirium tremens, hyper-hidrosis (profound sweating) and extreme disorientation. The protective effects of Mentat on the nervous system and brain function could even be useful for treating opiate withdrawal symptoms. Experiments have demonstrated that Mentat could prevent tolerance to the analgesic effects of morphine, thereby making the drug more effective. This suggests that it could have a beneficial role for treating opiate addiction (Kulkarni & Sharma 1994; Kulkarni & Verma 1992, 1993).

Leprosy: Disease and Disfigurement Acorus calamus. A compound preparation composed of the three herbs Centella asiatica (1 g), Acorus calamus (380 mg) and Convolvulus pluricaulis (20 mg) was trialled for the treatment of low-grade mental disability in children. These herbs have good tonic, neuroprotective and mild sedative properties. The course was long term (a year) and appreciable improvements were noted in verbal communication and concentration skills. The mixture also had an anti-anxiety effect useful for reducing hyperactivity and aggressive tendencies, thereby improving the children’s attention span (Rajagopalan 1995). (Image courtesy JeanFrançois Gaffard, CC-by-SA)

Leprosy rates among the most challenging and distressing of disorders in the history of medicine. The condition has always merited serious concern, with a diverse array of herbal remedies being used for its treatment – with varied levels of efficacy. This condition not only involves infection by a microbe that is difficult to treat, but poses numerous clinical problems. The infection can easily develop drug 8 Early research on the anti-epileptic effects of Bacopa only showed anticonvulsant effects at high doses in animal studies, some of which involved injectable formulations (Altern Med Rev 2004). However, later investigations have concentrated on different mechanisms of action which support its clinical use (Mathew 2011, 2010a, 2010b, 2010c, 2010d; Pandey 2010; Krishnakumar 2009; Khan 2008; Paulose 2008).

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Hospital. Six years later he wrote of his investigations in the Australasian Medical Gazette: At that time no medical man of the place was aware that he had seen a case of leprosy. The article in Erasmus Wilson’s book on skin diseases was in our hands, but in no work accessible to the ordinary travelling practitioner was there a plate or drawing of leprosy in any of its forms. Danielssen and Bocck’s book was out of print, and it was many years later that I had the opportunity of perusing that work in the library of the College of Surgeons, London. The illustrations there are valuable, and it is much to be regretted that no medical author in England had reproduced the plates in the class-books of the day. Had such been the case, the English medical student would have been able to diagnose ordinary well-marked cases of leprosy with readiness (Bancroft 1892).

Engraving by Gustave Doré illustrating the parable of the rich man and Lazarus (1891), from the Gospel of Luke. The beggar Lazarus, ‘full of sores’, died friendless and scorned on the steps of the rich man’s house, with only the dogs to lick his wounds. Lazarus was rewarded in the afterlife, while the rich man was not. Lazarus was later adopted as the patron saint of those suffering leprosy – an apt choice as lepers were shunned as society’s outcasts. ‘Lazar houses’, which were to become their refuge, were established across Europe during the twelfth century by the Military and Hospitaller Order of Saint Lazarus of Jerusalem. Many of the knights of this order suffered the condition.

resistance, it is contagious, and affects multiple organ systems. The integrity of the immune system is an important consideration that will affect treatment options. Complete success was virtually unknown until the advent of effective antibiotic therapy against the mycobacterium responsible (Mycobacterium leprae), and over the centuries herbal remedies were the only treatment available. It is hard to imagine the hardships faced by those who became infected, and by the clinicians who tried to ease their suffering. In the early days in Australia, the diagnosis was seriously hampered by a lack of information about leprosy. It was difficult to categorise because no one had encountered it clinically. The medical profession therefore lacked experience in treatment protocols. In 1866 Dr Joseph Bancroft began work at the Brisbane

His observations led Bancroft to diagnose leprosy in one individual – which eventually led to his interest in the control of filariasis. He initially thought that ‘leprosy and filaria were associated diseases, brought here by the Chinese, and distributed by mosquitoes carrying the diseased blood to water-tanks and elsewhere’. But while the puzzle of the transmission of filariasis and malaria were ultimately shown to be dependent on mosquitoes, leprosy was of bacterial origin.

The leprosarium on Channel Island. Australian islands were among the first choice of isolation outposts for those suffering leprosy. They included Peel Island in Moreton Bay (Brisbane), Fantome Island (Palm Island group, Townsville), and Channel Island in Darwin Harbour (Northern Territory). In 2007, Peel Island was declared the Teerk Roo Ra National Park and Conservation Park. (Image from ‘Scenes from the North Australia Patrol and other general scenes’, 1937–1942, by John Flynn, 1880–1951. Part of the Australian Inland Mission collection, c. 1912 – c. 1955)

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View of Orpheus and Fantome Islands, from Palm Island. (Courtesy Luke Duyvestyn, Wikipedia, CC-by-SA 3-0)

Remnants of the leprosarium settlement on Fantome Island. (Courtesy Debra Kerswill)

  Leprosy in Australia

Leprosarium, Darwin, 1958. (Courtesy W Pederson)

The story of leprosy is always associated with tragedy. There is no real evidence of leprosy in Australia prior to the arrival of Europeans. One of the earliest cases was that of a ship’s steward in Sydney Hospital in 1853. The incidents that followed were all discovered in Chinese immigrants – in 1855 in Queensland, and three years later in Victoria. However, it was another twenty-five years before cases were recorded in the Northern Territory (1882) and, soon afterwards, in Western Australia (1888) (Britton & Hargrave 1993). It is really no surprise that those suffering this disfiguring and infectious disease were treated with disdain and banishment just about everywhere around the world. Prior to the development of effective antibiotic therapy, segregation was the only way that transmission could be controlled. Attitudes were no different in Australia. Bancroft (1892) wrote: ‘It is a matter for satisfaction that so few cases of leprosy have happened in Queensland to persons of European extraction, but there is good reason to conclude that, without the measures that are carried out to remove Asiatic and Polynesian lepers to a considerable distance from the residences of the colonists, the disease would spread amongst ourselves.’ In the southern states the segregation between European, Chinese and Aboriginal communities appears to have worked to the advantage of all concerned as leprosy failed to fully establish itself in the community. By the turn of the century, new cases in New South Wales and Victoria primarily involved immigrants and refugees, mainly from Southeast Asia, who occasionally reintroduced the disease to Australian shores. The other states showed a different pattern of infection. Queensland had an influx of cases in the late 1800s (starting in 1896) with indentured Melanesian labourers (Kanakas). Subsequently leprosy became endemic – affecting Chinese, Melanesian and European communities. A peak occurred in the 1930s, and again in the 1980s, when there were outbreaks among the Torres Strait Islanders. Between 1950 and 1990 a total 929 cases were

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Article from The Star, 10 June 1891, Christchurch, New Zealand.

reported throughout the country, with 50 per cent occurring in Aboriginal people. In Western Australia and the Northern Territory, Aboriginal communities likewise suffered seriously from the disease as it was progressively passed from tribe to tribe – with a profound adverse impact on Aboriginal health. It peaked in the 1950s–1960s, after which its incidence gradually declined. Today most new cases are found among immigrants (Britton & Hargrave 1993). In the period 1991–2011 a total of 190 cases were reported Australiawide (National Notifiable Diseases Surveillance System, April 2012).

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Gotu Kola, at one time, was foremost among the herbal remedies that had a substantial reputation in the treatment of leprosy. Len Webb recorded the following in 1948: ‘A new method of treating leprosy is reported from Madagascar. A glucoside named “asiaticoside” is thought to be the active principle. It is insoluble in water, barely soluble in alcohol but dissolves well in pyridine. Solutions have been injected and the results so far are said to be remarkable. Boiteau & Grimes consider that the glucoside probably acts by dissolving waxy capsule of the Lepra bacillus, thus exposing it to attack by defensive agents of the body and other drugs.’  Asiaticoside not only had activity against Mycobacterium leprae, it was also active against the tuberculosis microbe (Mycobacterium tuberculosis) and the protozoan responsible for amoebic dysentery (Entamoeba histolytica) (Oliver-Bever 1986). Research has subsequently verified antimicrobial properties against both gram-positive and gram-negative bacteria – including Staphylococcus aureus, and its drugresistant (MRSA) forms. It has also demonstrated antifungal potential (Ullah 2009; Zaidan 2005) (see Table 4.2 for details). Asiaticoside was injected into leprotic nodules and perforated ulcers, and could be used to treat lesions that developed in sensitive areas such as around the eyes and on the fingers. In combination with antibacterial sulphonamides (formerly known as ‘sulpha drugs’) it was reported to be extremely successful in the treatment of leprosy – with clinical results comparable to the use of dapsone. Asiaticoside treatment was found useful for interstitial keratitis (inflammation of the cornea of the eye), which was said to clear completely in lepers suffering the disorder. Experimentally, asiaticoside could promote wound healing in skin tuberculosis and lupus tuberculosis (lupus vulgaris, nodular tuberculous skin lesions). Furthermore, Madecassol (a proprietary asiaticoside-containing preparation) was employed in the treatment of gangrene, and showed potential benefits for lupus erythematosus, a chronic autoimmune inflammatory disorder characterised by arthritis, fevers, skin rashes, photophobia and fatigue. Another study demonstrated that Centella asiatica was successful in the treatment of lesions due to schistosomiasis parasites when given by intramuscular injection (Kartnig 1988).

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A couple of aromatic herbs in the genus Plectranthus have been utilised for a variety of skin disorders including leprosy – P. laxiflorus (pictured here) and P. vettiveroides (Waldia 2011; Lukhoba 2006). Plectranthus amboinicus has a similar reputation, as well as being used in Brazil for treating the ulceration associated with leishmaniasis infection (Franca 1996). This herb has shown anti-mycobacterial activity that was associated with its diterpene components. Investigations continue to examine diterpenes (and derivatives) from these species for the development of drugs useful against drug-resistant mycobacteria (Rijo 2010; Frame 1998). A combination of Plectranthus amboinicus and Centella asiatica as a wound dressing to promote healing has shown good results in diabetic ulcer patients, comparable to the use of a hydrocolloid fibre dressing (Kuo 2012; Wu 2007; United States Patent 20070237841). (Image courtesy Bart Wusten)

Kemiri nuts (Aleurites moluccana), which contain a large amount of oil, were pounded to a paste for application to skin sores and ulceration.

The Leprous Affliction   Ancient Nemesis in the Modern World

In Indonesia a mixture of the Beach Sunflower (Wedelia biflora), Kemiri nuts (Aleurites moluccana) and Turmeric rhizome was considered among the most effective of the traditional remedies used for leprous wounds. The Beach Sunflower has been widely used as a wound-healing agent in Southeast Asia – the leaves (or the fresh juice squeezed from them) were regarded as being highly effective (Elliott & Brimacombe 1987). (Image courtesy Phuong Tran, flickr)

Photomicrograph of Mycobacterium leprae taken from a leprotic skin lesion. (Courtesy CDC, US Government Public Health Image Library)

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Leprosy has been a highly distressing affliction throughout human history. The Ancient Egyptians were familiar with it, as the disease is known to have been present in the Nile Valley before 1500 BC.9 It is even mentioned in the Bible. Since then the condition has been universally regarded with justifiable fear and loathing. It was probably introduced into Europe with the Roman soldiers, and later reintroduced by returning Crusaders. Its spread throughout the rest of the world occurred as travellers migrated from the primary focal points of infection – Africa, China and Norway. The disfiguring course of the disease has always been a great impediment to social survival for afflicted individuals. Added to this was the abject terror associated with the contraction of such a visually confronting disorder – the status of ‘outcast’ was certain, an all too terrible reality for sufferers. Contamination control was seriously hampered by the fact that some individuals could be carriers of the infection for many years before it manifested, providing an active reservoir of infection. The uncertainty regarding one’s susceptibility compounded the problem of diagnosis, treatment and preventive measures: ‘The incubation period is difficult to determine in many cases. Long exposure is required for infection, and latent infection may persist for years. Furthermore, the onset may be so insidious that early symptoms are often disregarded. Estimates extend from a few months to thirty or more years’ (Musser 1938). The incubation period of leprosy in most patients however, ranges from 3–7 years (Walsh 2010). Today, leper colonies are generally regarded as a mere memory – shunned groups of individuals suffering a condition that no longer exists. The reality of the situation is somewhat different. While leprosy is one of the oldest known diseases, its modern significance has been largely ignored – even though the health implications continue to be dramatic. At the beginning of 2000 the number of leprosy patients worldwide was over 6.5 million, in 91 countries. Considerably more are at risk of contracting the disease. In the 28 countries with the highest incidences, the

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rate is one case per thousand people. The total population of these countries is 1,320 million, and many of the inhabitants are more than likely to come in contact with the disease. The greatest concentration of cases is in Southeast Asia, particularly India. A staggering 500,000 new cases were discovered in 1990 and over 680,000 new cases diagnosed in 1999. The situation has, fortunately, improved substantially, with 244,796 new cases recorded in 2009. Over 70 per cent of the world’s leprosy sufferers reside in India, Indonesia, Bangladesh and Myanmar (formerly Burma). Brazil and Nigeria also have significant numbers of registered cases. However, authorities worry that possibly no more than one-third of those suffering from the infection have been detected in countries where health facilities are poor, and programs to diagnose the disease are equally inadequate (WHO 2010; ILEP 1994; Britton & Hargrave 1993). 9 It appears that leprosy originated in Africa and migrated to India in prehistoric times along trade routes between the Indus Civilisation, Mesopotamia and Egypt. A recent investigation of skeletal remains from northwest India has confirmed its presence here by 2000 BC – and the condition was reported in ancient Vedic scriptures (Robbins 2009).

Dr GH Armauer Hansen discovered the bacterium responsible for leprosy, Mycobacterium leprae, in 1874 – hence, leprosy is also referred to as Hansen’s disease. The microbe was found to be spread by droplet infection10, primarily via respiratory secretions: Bacilli are widely distributed in the bodies of lepers. They are found in large numbers in the skin lesions, peripheral nerves, liver, spleen, lymph nodes, kidneys and endothelium, often within ‘lepra cells’. Bacilli appear in the blood at times during fever, and are found with great regularity in the nasal secretions or scrapings of many patients. The saliva and other secretions and excretions serve as a vehicle for the exit of bacilli from the body. Lepers are regarded as dangerous only if they are ‘open’ cases, cases in which there are discharging ulcers or in whom Lepra bacilli can be demonstrated in excised tissues, 10 Mycobacterium leprae is present in the soil in some areas, which makes some animal contacts a matter of concern. Indeed, in the United States naturally-infected wild armadillos act as a reservoir for the disease (Walsh 2010).

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scrapings or in secretions or excretions. Persons with old ‘healed’ lesions like those with healed tuberculosis are no menace and need not live in strict isolation. It must be borne in mind, however, that persons regarded as cured or even persons who have never shown any evidence of the disease, may harbour bacilli. Such instances are considered as latent infections, in which the disease may flare up at any time (Musser 1938).

Much depends on the integrity of the immune system in a person exposed to Mycobacterium leprae. Remarkably, a high percentage of infected individuals can mount an effective immune response to the disease and do not develop the clinical signs of leprosy. Indeed, in most endemic areas only 5–10 per cent of infected people progress to clinical disease.11 In those who do, the status of the immune system is of paramount importance and will determine the progression of the disorder (see also Walsh 2010). There are two forms of the disease:

be affected by the mycobacterium and would benefit from herbal intervention: adaptogens such as Turmeric (Curcuma longa) and Withania (Withania somnifera) can provide general system support, while St Mary’s Thistle (Carduus marianus) and Dandelion (Taraxacum officinale) have a potent protective effect on liver function. Indeed, a study of the hepatoprotective role of an Indian herbal combination remedy known as Liv-52 has supported its traditional use for liver function in leprosy12 (Nigam 1982). For neurological dysfunction Gotu Kola and Brahmi (Bacopa monnieri) would be appropriate. Doubtless many of the traditional formulations used in treatment protocols were based on a system supportive role.

•  Firstly, tuberculoid leprosy, which is the less infectious. It is associated with strong immune system defences and a limitation of skin and nerve damage. • The second form is lepromatous leprosy, where there is more extensive proliferation of the bacillus. While there are no signs at the beginning, this is much more contagious: ‘Lepra bacilli may invade any tissue or organ in the body, but, like the spirochete of syphilis, have a predilection for skin and nerve tissue. In this respect, the biologic behaviour is in contrast with that of the closely related tubercle [tuberculosis] bacillus which seldom invades skin or nerve tissue’ (Musser 1938). It is characterised by more extensive skin lesions and serious neurological damage. 11 In addition, treatment of HIV has the potential to increase the incidence of leprosy in areas where the latter condition is endemic (Walsh 2010).

  Herbal Immune Tonics The benefits of immunosupportive medicines have gained greater prominence in modern medicine. Remedies such as Echinacea (Echinacea angustifolia, E. purpurea) and garlic (Allium sativa) are, once again, achieving recognition. In the case of leprosy, numerous body systems can

Turmeric (Curcuma domestica syn. C. longa), from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

12 Liv-52 contains Mandur Basma (iron oxide), Tamarix gallica and herbal extracts of Capparis spinosa, Cassia occidentalis, Cichorium intybus, Solanum nigrum, Terminalia arjuna and Achillea millefolium. It has gained a good clinical reputation for the treatment of cirrhosis. Its efficacy was attributed to a number of effects – diuretic, anti-inflammatory, antioxidant and immunomodulating activities (Huseini 2005).

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Turmeric powder. (Courtesy Sanjay Acharya, Wikimedia Commons, CC-by-SA 3.0 Unported)

The lovely Echinacea purpurea is a premier immune-supportive remedy with an outstanding clinical reputation.

Turmeric has long been a popular household healing remedy with significant antibacterial, antiseptic and anti-inflammatory attributes. Much of this activity is linked to the main flavonoid, curcumin, and extensive research has been undertaken on its activity, particularly as an anticancer agent. Recent studies have shown that Turmeric has good antimycobacterial activity, which appears linked to curcumin and

certain derivatives, some of which have shown potential against drug-resistant Mycobacterium tuberculosis (Changtam 2010; Agrawal 2008; Leal 2003). Other species, such as the Mango Ginger (Curcuma amada), have similar potential (Singh 2010). Although it appears that virtually nothing is known about the medicinal attributes of the Australian species Curcuma australasica, it appears likely that it would have comparable antibacterial properties.

The Cape York Lily, Curcuma australasica, is found in northern Queensland (primarily Cape York), ranging to nearby sites in the Northern Territory and overseas to Papua New Guinea. The root, which has been used as a roasted vegetable by Aboriginal people, has a very similar appearance to that of Curcuma longa. The Cape York Lily was familiar to the early botanists. It was discovered by a Mr John Veitch and introduced into English horticulture, with an illustration of the herb published in the Botanical Magazine of 1867.

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Clinically, leprosy presents with a broad spectrum of symptoms. Initially they can be mistaken for common malaise: rhinitis, fever, fatigue, somnolence, headache, anaemia, vague muscle aches and pains. Skin lesions and nerve pain (neuritis) manifest to varying degrees. Eventually, progressive nerve damage results in an inability to feel properly, with a disruption of blood supply and severe muscle weakness. Later damage can affect the bones, with the development of secondary infections (osteomyelitis), while joint problems result in deformities of the hands and feet (wrist and foot drop, clawing of the toes or hands). Facial damage is particularly distressing. This includes paralysis of the facial nerve and infection of the cartilage of the nose – which may develop into a saddle-nose deformity (collapsed ‘bridge’ cartilage) and ulceration. Eye involvement also involves ulceration of the cornea – followed by infection, glaucoma or blindness. Homoeopathic preparations of Leprosinum remedy. This is utilised for conditions with a ‘leprotic’ symptomology, particularly skin conditions such as vitiligo, ringworm, skin nodules or lumps, ulceration, psoriasis, and some forms of eczema. It can also be appropriate for neurological problems (neuritis, numb-ness, tingling), hair loss, general itching (pruritis) and limb deformities, notably where there is nervous system involvement. It is particularly indicated from problems that do not respond to regular treatments (for greater detail regarding this remedy see The New Materia Medica Volume 2: New Key Remedies for the Future of Homeopathy, Colin Griffith, 2011). (Image courtesy Martin & Pleasance, Port Melbourne)

The more dramatic physical effects of leprosy can engender great disfigurement: The development of subcutaneous nodular infiltrations which often appear in the sites of the first skin eruption … The nodules most commonly involve the face, back of the hands and feet, but rarely the scalp. Loss of facial hair and beard occurs. As the nodules enlarge the skin becomes deeply furrowed; the ear lobes, lips and nose become thickened, tending to cause a resemblance to a lion’s face. The nodules appear in crops and are accompanied by leprous fever. Some may disappear, while others

continue to increase in size and cause great deformity. The infiltration may spread to other parts of the body surface. The general appearance of the skin is unhealthy. It is often dusky or ‘muddy’, dry or scaling. The nails are often striated. Ulcerations occur rather easily. Ulcers may heal, but often penetrate deeply and spread, causing appalling mutilation. Various digits may drop off. Nodular infiltrations and ulceration of the mucous membrane lead to hoarseness and aphonia (Musser 1938).

There may be associated inflammation of the kidneys and liver, tuberculosis, pneumonia and orchitis (testicular inflammation). In cases where the disease primarily affects the nervous system: [t]he nervous symptoms may appear very gradually and are most often accompanied by the development of round or irregular varicolored skin plaques … The involved areas are first hyperaesthetic [hypersensitive], later anaesthetic. Pruritis [itching] and neuralgic pains occur … Anaesthesia [loss of feeling] often commences peripherally and extends centripetally. Anaesthesia may be complete. Burns and other traumata often incite the formation of ulcers which tend to become deep and mutilating. Secretory and trophic disorders are common. Trophic ulcers of the soles of the feet are common. Atrophy of muscles occurs, often affecting the muscles of the hand. The contracture leads to the characteristic ‘claw’ hand. Gangrene or ulceration of the extremities or other portions of the body cause severe deformity (Musser 1938).

Leprosy Treatment

Dapsone is a sulfone antibiotic that was synthesised in 1908 and became the keystone of modern advances for the effective treatment of leprosy. Its development was, however, hindered by experimental toxicity until a breakthrough in 1941 led to the development of promin (a gluco-sulfone derivative) with a remarkable antimycobacterial effect. Following this, a form of dapsone (DDS: diamino-diphenylsulfone) was found to be effective. Fortunately, it had minimal side-effects and was cheap to produce. Later treatment advances lead to the development of effective antibacterial agents such as rifampicin, ethionamide/prothionamide and clofazimine. In the 1980s the World Health Organization advocated the widespread adoption of a combination antibacterial protocol that was found highly effective and continues in use today.

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This illustration shows MDT (multidrug therapy) regimens for the treatment of leprosy (World Health Organization, 2000).

The Legendary Chaulmoogra

Chaulmoogra oil (sourced from the fruit of various Hydnocarpus species, including H. pentandra) has its origins in legendary times, having been utilised by Indian medicine for more than 2000 years. Old Chinese medical texts also mention the oil, which was introduced from Siam in the fourteenth century. (Images courtesy Pierre Grard, Biotek, French Institute, Pondicherry, India)

For centuries leprosy treatments were based on the use of Chaulmoogra oil from Southeast Asia – a remedy that was employed by both Chinese and Indian medical traditions. Chaulmoogra oil deserves continued recognition as a valuable therapeutic agent

– despite the fact that the successful development of sulfone drugs in the 1940s saw its use abandoned. Initially, Chaulmoogra oil came to the attention of Western physicians in the 1850s, through the reports of Dr FJ Mouat of the Bengal Medical Service. The

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remedy gained a measure of medical acceptance – although its popularity soon waned, probably due to the revolting taste. The 1899 Squire’s Companion to the British Pharmacopoeia noted the use of ‘Chaulmugra Oil’ in a variety of conditions: psoriasis, obstinate eczema, and various irritant skin diseases, chronic rheumatism, gout and secondary syphilis. Good results were noted with its use (internal and external) for phthisis (tuberculosis). Later improvements in its preparation and administration resulted in a resurgence of interest in it as a leprosy treatment. In the 1930s the oil was once again in widespread use – and continued to be favoured until its eventual replacement by newer drugs. The general opinion regarding its efficacy is given by the Martindale Extra Pharmacopoeia (1941): Chaulmoogra oil is employed almost exclusively for the treatment of leprosy. It is not a specific, but with prolonged treatment (extending over several years) it results in so complete an arrest of the disease as to produce an apparent cure in a very considerable proportion of cases. It may be given by mouth (in capsules after meals), by intramuscular injection or by intradermal infiltration, or by a combination of these procedures. It has also been employed in pulmonary tuberculosis, but there is no convincing evidence of its clinical value, though successful results are claimed for its use by local application in tuberculous pharyngitis.

The oil was also often recommended in the treatment of syphilis. The healing value of Hydnocarpus was noted to be substantial: [it promoted] the disappearance of the macules; [with] initial swelling of the nodules, then softening, contraction, and complete cicatrization; improvement of sensation; decreased swelling of the nerves; healing of the ulcers, disappearance of the bacilli from the nasal mucus and the blood; improvement of general health. The response of early cases requires three months of energetic treatment; three to six months with moderately advanced cases (BPC 1963).

Unfortunately, the nutritional and immunological status of the patient does not appear to have been addressed. Diet can have a huge impact on health, particularly on the integrity of the immune system – therefore nutritional influences could well have been an important neglected component of the problem.

It also suggests that many herbs, which we now know have immune system supportive effects, could have played a valuable therapeutic role. There was the suggestion that Chaulmoogra oil also had anti-arthritic potential, although this was not subjected to investigation. However, there is a report by Dr Ernest Fletcher in 1940 that mentions: It was found that these ethyl esters [chaulmoogric and hydnocarpic acids] of chaulmoogra oil were of little value in either of the main groups of arthritis; and chaulmoogra oil itself was therefore tried. Small series of cases of rheumatoid or infective arthritis (which we are unable at present to distinguish satisfactorily) were not sufficiently impressive to justify its continuation and it was decided to try the oil in cases of osteoarthritis. After two years’ experience it seems that the results are sufficiently good to be set down in detail.

The treatment involved intramuscular injections into the buttocks. Initially this was a painful procedure until a local anaesthetic was incorporated. The trial was small (20 patients), but around 75 per cent responded extremely well to the treatment. The author concluded: ‘Chaulmoogra oil is found to be superior to any other single medicament in the treatment of osteoarthritis, but to have a very limited field in cases of rheumatoid or infective arthritis.’

  Difficulties with Identification The Hydnocarpus genus contains over forty species of rainforest trees that range from India and Sri Lanka in the west, to the Philippines and Indonesia in the east.13 For a long time, the original source of Chaulmoogra oil was difficult to identify as, in the absence of leaf or flower samples, scientists had no real idea of the correct botanical description of the tree. Consequently the plant’s 13 In recent times the reshuffle of the Flacourtiaceae, which was a complete botanical muddle, resulted in the various genera being placed in several families. The Flacourtiaceae itself was redefined as a tribe within the Salicaceae family. The Southeast Asian Hydnocarpus was among the thirty genera previously classified in the Flacourtiaceae that were transferred to the Achariaceae. Hydnocarpus contains the greatest number of species (40) in this classification, with Ryparosa being the next largest (19). The genera Caloncoba and Carpotroche are also classified in the Achariaceae. Interestingly, fourteen Achariaceae genera are monospecific (i.e. they contain only one species), indicating that a high level of unique floral characteristics occur within this classification (Meredith Cosgrove CSIRO pers. comm March 2011; Webber & Woodrow 2005).

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identification, and the subsequent isolation of the active principles, did not occur until late in the 1800s. Only a few species are suitable for use: • Kalaw, Hydnocarpus kursii (syn. Taraktogenos kurzii) from the jungles of Burma was in the greatest demand. • Tuvaraka, Hydnocarpus pentrandra (syns H. laurifolia, H. wightiana), from southern India was abundant and accessible, which led to its more widespread use.

A couple of other genera yielded oil alternatives of a similar quality to Hydnocarpus. They included (above) Godi (Caloncoba echinata, syn. Oncoba echinata) from Central Africa (Sierra Leone, Ivory Coast, Guinea), and (below) the South American Sapucainha (Carpotroche braziliensis) from the east coast of Brazil. (Upper image courtesy Susan Ford Collins, flickr; lower image courtesy Luis Bacher, flickr) Hydnocarpus kunstleri (leaf, trunk) from Sumatra and the Malay Peninsula, growing in the Flecker Botanic Gardens, Cairns. This was one of the species utilised as a Chaulmoogra oil resource in Indonesia and Malaysia. Chaulmoogra cultivation even spread to Australia, where Hydnocarpus laurifolia (syn H. wightiana) was introduced into tropical north Queensland as a plantation crop in the hope of local oil production. The tree can still be found growing in the northern suburbs of Cairns.

•  The deployment of various local species depended on their availability and location. They included the Chinese Tai-fung-tze, Hydnocarpus anthelmintica (syn. H. alpina); Dudo or Dudoa (H. alcalae) was utilised in the Philippines; H. macrocarpa in southern India; Makulu (H. venenata) in Sri Lanka; and H. castanea in the Burma/Malay Peninsula region.

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Oils extracted from Hydnocarpus anthelmintica, H. wightiana, H. ilifolia and H. kurzii were regarded as having very similar anti-leprotic properties.14 The seeds had to be cold-pressed – that is, crushed and the oil extracted without the use of heat. Little appears to be known about the dietary incorporation of the oil, although its early use was severely limited by gastrointestinal irritation. Indeed, in 1922 the California State Journal of Medicine commented in an editorial: ‘This oil is, however, so nauseating and causes such serious digestive disturbances that few patients are able to continue the treatment long enough and intensively enough to obtain therapeutic results. Nevertheless, the literature records a considerable number of cases of leprosy improved, arrested and even apparently cured by this method of administration’. 14 Chopra (1956) also mentions that the seeds of H. alpina, H. octandra, H. odorata (syn. Gynocardia odorata) and H. venenata were utilised for the treatment of leprosy. Burkill (1935) adds H. ilicicolia and H. kunstleri. Hydnocarpus alpina leaf extracts have shown insecticidal (antifeedant and larvicidal) activity against the Asian armyworm (Spodoptera litura), an agricultural crop pest. The oil had a more potent activity when combined with Neem oil (Azedarachta indica) (Vendan 2010).

Gynocardia odorata, from William Roxburgh and Sir Joseph Banks, Plants of the Coast of Coromandel, Vol. 1, W. Bulmer & Co, London, 1795.

A Matter of Chemical Clarity The story of Chaulmoogra is characterised by a classic case of botanical misidentification that was to cause substantial confusion with its subsequent chemical analysis. It all began with a simple case of mislabelling. In 1879 seeds of a species of Hydnocarpus (probably H. kurzii) were wrongly labelled as Gynocardia odorata, and thus, in the older texts, the oil is often listed under ‘Gynocardia’. Chemical evaluation isolated a mixture of fatty acids, which were, quite naturally, named gynocardic acids. When the botanical differences between the seeds and the extracted oils of Hydnocarpus and Gynocardia were eventually resolved, the seed oils were found to be distinctly different. In 1881, Dr Wyndham Cottle of London experimentally used ‘gynocardic acid’ extracted from Chaulmoogra oil for the treatment of conditions such as leprosy, psoriasis, eczema and lupus. Only later, when the active compounds were properly isolated, were they named chaulmoogric and hydnocarpic

The tree Gynocardia odorata belongs to the same family as Hydnocarpus, the Achariaceae. The fruit was once, mistakenly, thought to be the source of Chaulmoogra oil. However, Gynocardia odorata oil was not found to contain chaulmoogric acid, but consisted of linolic and linolinic [sic] acids – a marked chemical difference. (Image courtesy Nandini Velho)

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acids (Quisumbing 1951). Chaulmoogra oils were unique because they contained a large amount of these two acids, although the ratio in the different species could vary considerably: • Dudoa (Hydnocarpus alcalae) from the Philippines: seed oil content 65.5%, with an abundance of chaulmoogric acid (90%), and little or no hydnocarpic acid. The seed oil was used in folk medicine for the treatment of rheumatism, tuberculosis, sprains and bruising (Quisumbing 1951). • Hydnocarpus laurifolia (syn. H. wightiana): seed 32.4% oil, containing hydnocarpic acid (48.7%), chaulmoogric acid (27%), gorlic acid (12.2%), oleic acid (6.5%) and palmitic acid (1.8%) (Chopra 1956). The acids were primarily accumulated during the last 3–4 months of fruit maturation. Experimentally they had strong bactericidal effects on Mycobacterium leprae (Evans 1992). This species was particularly valued because the seeds gave a fairly high yield (twice that of H. anthelmintica) and provided a far purer oil than that derived from the other species (Burkill 1935). • Hydnocarpus anthelmintica: seeds 16.3% oil (kernel 64.8–65.5% oil), containing hydnocarpic acid (67.8%), chaulmoogric acid (8.7%), gorlic acid (1.4%), oleic acid (12.3%) and palmitic acid (7.5%) (Chopra 1956). H. anthelmintica oil was useful for scabies, scalds, rheumatism and gout. The seeds served as a vermifuge15 and as a remedy for smallpox, while the bark has been incorporated into a decoction to treat urinary incontinence (Perry & Metzger 1980). • Hydnocarpus kurzii (syn. Taraktogenos kurzii): seed 30.9% oil, containing hydnocarpic acid (22.5%), chaulmoogric acid (22.6%), gorlic acid (14.6%), oleic acid (14.6%), palmitic acid (4%) (Chopra 1956).

15 This species has shown good experimental anthelmintic activity against the roundworm, Ascaris lumbricoides (Raj 1975).

Carpotroche brasiliensis, from Flora Brasiliensis, 1886. This species, which belongs to the same family as Hydnocarpus (formerly Flacourtiaceae, now Achariaceae), contains an oil with comparable fatty acid components: hydnocarpic acid (40.5%), chaulmoogric acid (1%) and gorlic acid (16.1%). Investigations have confirmed the antiinflammatory and analgesic (antinociceptive) activity of oil extracts, thereby providing good support for the traditional uses of the remedy and its use as an anti-leprotic agent (Lima 2005). The seeds of Carpotroche brasiliensis also contain cyanogenetic glycosides (gynocardin, tetraphyllin B) (Spencer 1982).

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Ryparosa kurrangii (formerly thought to be R. javanica). Ryparosa is a small genus of nineteen trees and shrubs that range from the Andaman Islands to Southeast Asia, New Guinea and Australia – some of which yield a useful timber. (Image below courtesy Neil Hewett, Cooper Creek Wilderness, Daintree National Park)

Chaulmoogra oil, from the Martindale Extra Pharmacopoeia, 1941.

Achariaceae in Northern Australia

There are only three representatives of the Achariaceae family in Australia – all are rare species from northern Queensland. Among them is a unique native Hydnocarpus, which has been collected in the ‘Possum Scrub’ of Cape York. The two other representatives are from the rainforest: • Baileyoxylon lanceolatum from the Atherton Tablelands is the only species in this endemic genus. • Ryparosa kurrangii (formerly classified as the Javan

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Ash, R. javanica or Ryparosa sp. Daintree) has a highly restricted distribution on the Daintree coast, north of Cairns. When various genera within the Flacourtiaceae were reassigned botanically, the majority of the taxa that showed cyanogenic activity were placed in the Achariaceae family. Thus it is no surprise that the Ryparosa genus contains these compounds. Indeed, gynocardin is a specific for some species, including Ryparosa kurrangii. This cyanide-based toxin can act as part of the plant’s defensive strategies, as cyanogens are respiratory toxins that deter various herbivores. Another native tree in this family, Baileyoxylon lanceolatum, contains the same toxin in its foliage (Webber & Miller 2008). Indeed, ‘Cyanogenic defence … forms just part of a formidable physical, phenological and chemical defence continuum that exists across a [R. kurrangii] leaf age gradient’ (Webber 2005).   However, the plant does not normally release cyanide, due to a separate cellular encapsulation strategy of the cyanide and the activating enzyme. They are only mixed (activated) when tissue damage occurs. The cyanide levels can vary considerably, being highest in the early floral tissue growth, in comparison to the leaf foliage. Young expanding leaves had higher levels than mature leaves – and there was significant seasonal variation. High concentrations were evident during the late wet season, with a lesser amount being found pre-wet season, when fruiting and leaf growth occurred. The latter possibly indicates its use as a stored nitrogen resource by the plant (Webber & Woodrow 2008; Webber 2007a). Mature Ryparosa leaves also produce lipid-rich food parcels (multicellular pearl bodies) that act as a reward for ants, and ‘may be invaluable for keeping long-lived leaves free from epiphyllous communities.’ This is probably a survival adaptation under the low-light conditions of the rainforest (Webber 2007b). Flower pollination appears to be primarily linked to beetle activity (Monolepta sp.), with potentially interesting aromatic attractants being utilised (Webber 2008).

Ryparosa javanica (as Bergsmia javanica), illustration by KL Blume, Rumphia, Vol. 4, 1848. Ryparosa javanica was originally thought to be a widespread species, ranging from Southeast Asia to New Guinea and Australia. It was, however, eventually determined to be a complex of at least nine species, and R. javanica itself is now considered to be confined to Sumatra, Java and Bali. Other species formerly classified as R. javanica are found in New Guinea (R. amplifolia, R. maculata, R. milleri); the Andaman and Nicobar Islands (R. kurzii); Myanmar, Thailand, Malay Peninsula and Sumatra (R. wrayi); western Borneo (R. anterides, R. maycockii); and northern Australia (R. kurrangii) (Webber & Woodrow 2006).

Baileyoxylon lanceolatum is an endemic rainforest tree of northern Queensland. (Courtesy Department of Botany, Smithsonian Institution)

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Rainforest Rescue is supporting the conservation of Cassowary habitat.

Cyanide in Pangium

There is another cyanide-containing Southeast Asian species now placed in the Achariaceae family that is of interest as a food resource – and for its poisonous reputation.16 Pangium edule is a long-lived mangrove tree that only starts to produce fruit after fifteen years. This harvest provides a good illustration of classic food-processing strategies, characterised by a great attention to detail, that have been utilised in the preparation of toxic foodstuffs. Henry Burkill (1935) recorded that: ‘The tree is poisonous enough for its name to be proverbial as an intoxicant; but the seeds are used as food, precautions being taken to prepare them in such a way as to remove the poison. The poison is hydrocyanic acid, which arises from the glucoside gynocardin, and pervades the plant. By boiling the seeds for an hour, the chemical interaction of the gynocardin and the accompanying enzyme gynocardase, by which the hydrocyanic acid is produced may be prevented; for the heat destroys the gynocardase.’ The ripe seeds contain less of the glucoside than unripe seeds, making the latter much more dangerous. 16 The toxic effects of cyanide are discussed in greater detail in Volume 3.

In many ways the survival of the Cassowary is integral to the long-term maintenance of the tropical Australian rainforest. Numerous unique native trees require transmission of their seeds through the bird’s gut for germination. This includes Ryparosa kurrangii, with germination levels improving from a mere 4 per cent (unprocessed or normal propagation strategies) to 92 per cent when passed though the Cassowary digestive system (recovered from Cassowary droppings). It was established that high levels of fruit-fly predation were linked to the poor seed-set figures, which was avoided when the Cassowary ate the fruit (Webber & Woodrow 2008; Webber 2007a). Unfortunately, there are high Cassowary fatality rates in urban and rainforest areas due to road traffic and dog attacks. Currently, few chicks survive to adulthood.

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The preparation process traditionally involved crushing the seeds, boiling them and putting them into running water for a day, after which they were re-boiled before being considered edible. Another method involved the boiled seeds being buried with ashes, thereby permitting a slow natural fermentation process that took around 40 days. Various other combinations of boiling and fermentation could be utilised to reduce the time taken. However, inadequate preparation has resulted in fatalities. Burkill also mentions their use as an antiseptic, the pounded seeds used for the preservation of fish, ‘placed inside the body after the entrails have been removed and over the fish also, much as ice in Europe’. The freshly crushed seeds were applied to boils in Malaysia, while the hydrocyanide-containing leaves were used as an antiparasitic agent for itching skin problems and festering wounds. He noted that the young leaves ‘contain more poison than old ones’ – with the latter being used in Sulawesi (formerly Celebes) to make a type of condiment, the old leaves shredded, mixed with pig’s blood and salt, then stuffed into a bamboo joint and boiled. The leaves were also said to have anthelmintic properties. The tree (bark, leaves, fruit) could be used as a fish poison

Pangium edule seeds. These seeds contain a toxic oil, albeit they are utilised for culinary purposes. This was only possible when the seeds were exposed to extensive processing. Their eventual use in cooking (exposure to heat) would have finally detoxified them enough for consumption – although the seed was noted to have poor keeping qualities, quickly becoming rancid (Burkill 1931). (Image courtesy Midori, Wikimedia Commons, CC-by-SA 3.0 Unported)

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– and also as a criminal poison (Burkill 1935). In Papua New Guinea the fruit was reputed to have been used for ‘homicidal purposes’ and to assist in stealing a neighbour’s fowls by killing the birds quickly before the deed was discovered (Webber & Miller 2008).

New Roles for Chaulmoogra Oil?

Modern drugs, without doubt, have been highly effective in the treatment of leprosy – although they have not been entirely successful in actively promoting wound healing. The advent of antibiotic therapies saw the use of Chaulmoogra oil gradually fade into obscurity. Even so, the question of its efficacy has remained unresolved in current scientific terms. Surprisingly enough, during the era of its use, rigorous evaluations involving comprehensive clinical trials were never undertaken. Investigations supporting the use of Hydnocarpus oil are relatively few, considering its widespread clinical use over such a long period. However, there are suggestions that the remedy has more to recommend it than has been hitherto appreciated by modern medicine. Accounts of leprosy patients taking Hydnocarpus oil capsules as a complementary healing agent have led a few studies to attempt a re-evaluation of the oil’s potential. It can facilitate wound healing in animals and this suggests that it could be a useful addition to the treatment of leprotic ulceration. Not only can Hydnocarpus oil promote the healing process, but it also strengthens tissue repair at the wound site (Oommen 2000, 1999). There are additional reports of its topical application or oral use by individuals with diabetic ulcers and gangrene that suggest more rapid healing can be achieved (Mankrekar 1996). Centella asiatica has similar benefits for wound repair. The suggestion that combined therapies might be useful in promoting the healing of lesions is not new. The British Pharmaceutical Codex of 1963 noted that hypopigmented lesions could be encouraged to repigment by intradermal injection into the lesion using Hydnocarpus oil ethyl esters and, in nonresponsive cases: ‘when adequate bacteriological improvement is absent, a course of intradermal injections of the esters is advocated as it has been shown that such injections combined with sulphone therapy may be more effective than sulphones alone’. Traditionally, Chaulmoogra oil was primarily

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Hydnocarpus pentandra. In Kerala, India, the seed oil of this species was mixed with the leaf juice of Madar (Calotropis gigantea) and applied externally for scabies and leprosy (Silja 2008). (Image courtesy Shubhada Nikharge, flickr)

utilised for wounds and skin problems, although substantial variations in its use in folk medicine were recorded. In India, Hydnocarpus wightiana (syns H. laurifolia, H. pentandra) was specific for skin complaints, wounds, ulcers, and in treating ophthalmia (eye disorders). The seed oil provided a local application for rheumatism, sprains, bruising, sciatica and chest infections (Krishnamurthy 1959). A combination of Chaulmoogra oil and cow’s urine could be prescribed for both internal and external use. In Indian veterinary practice, Chaulmoogra oil was applied to saddle sores and provided a liniment (Kapoor 1990; Burkill 1935). In Burma, a bark decoction of Hydnocarpus castanea (H. kurzii subsp. australis) was taken for ‘internal disorders’, as well as for skin diseases (Burkill 1935). There are hints that Hydnocarpus oil may continue to have some practical value in modern therapy. While recent investigations are fairly rare, in 1983 an interesting paper mentioned that Chaulmoogra oil (and some other oils) stimulated the immune system in mice, particularly against Mycobacterium leprae. Therefore it was possible that unsaturated fatty acids could augment the chemotherapy employed in leprosy management (Wemambu 1983) – a suggestion that appears worthy of serious evaluation. Certainly, it has been shown that a combination of Hydnocarpus oil and dapsone had an additive inhibitory effect on the growth of Mycobacterium leprae (Desai & Bhide 1977). Another investigation that supports antibacterial properties for Hydnocarpus anthelmintica (syn. H. anthelminthica) seed extracts identified flavonolignans (anthelminthicins A, B, C), chaulmoogric acid and ethyl-chaulmoograte as possessing significant

Colourised scanning electron micrograph (SEM) of Mycobacterium tuberculosis. (Courtesy Janice Haney Carr, CDC)

Mycobacterium tuberculosis is an acid-fast bacterium (AFB), and is therefore undetectable when stained using a gramstain technique. However, using SEM, the M. tuberculosis bacteria glow yellow under ultraviolet light microscopy. (Image courtesy CDC)

activity against the causative agent for tuberculosis, Mycobacterium tuberculosis (Wang 2010). Flavonolignans from the genus have a variety of pharmacological properties. Those from Hydnocarpus wightiana seeds (hydnowightin, hydnocarpin and neohydnocarpin) have shown a substantial ability to lower cholesterol levels and displayed anticancer activity against a range of cancer cell types. Moreover, hydnocarpin exhibited good experimental antiinflammatory and anti-neoplastic activity in mice, as well as cytotoxic properties (Sharma & Hall 1991). Recent studies have confirmed the antiinflammatory potential of flavonolignans and have isolated a new compound (anthelminthicol A) with similar potential from Hydnocarpus anthelmintica seeds (Wang 2011). Hydnocarpus annamensis contains phenolic glycosides with anti-inflammatory and antioxidant properties (Shu 2006). Equally

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interesting is the isolation of a number of cytotoxic compounds (mycoepoxydiene and derivatives, deacetylmycoepoxydiene) from a broth extract of an endophytic fungus (a species of Phomopsis) found on Hydnocarpus anthelmintica (Prachya 2007). In addition, traditional Indian medicine recommends the seed hulls of Hydnocarpus wightiana as an antidiabetic remedy.17 Investigations found extracts contained substantial amounts of hydnocarpin, isohydnocarpin and luteolin – all of which had strong antioxidant and radical-scavenging properties, as well as enzyme-inhibitory activity, that could influence the effect of the herb on regulating blood sugar levels (Reddy 2005).

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that 5’methyoxyhydnocarpin18 from this herb does not, itself, have antibacterial properties – although it can potentiate the antibacterial effects of berberine against Staphylococcus aureus. Equally intriguing was the finding that a number of berberine-containing plants were able to synthesise 5’methoxyhydnocarpin to maximise their antibacterial defences – allowing them to inactivate and overcome the bacterium’s resistance strategies (Stermitz 1999).

Hydnocarpus: Flavonoids of Pharmacological Value

Flavonoids, which have extremely diverse pharmacological potential, are the primary active components of a number of highly valued medicinal herbs. They can also interact within a plant extract in some interesting ways, about which relatively little is known. With regard to the Hydnocarpus genus, hydnocarpin and luteolin are of particular interest as both compounds have shown anticancer activity.  Anticancer (cytotoxic) activity has been reported for hydnocarpin against various cancer cell lines (leukaemia, nasopharyngeal carcinoma, colon adenocarcinoma, uterine carcinoma, bone osteosarcoma) – and, importantly, it has shown a synergistic effect with the anticancer drug vincristine. This is certainly worthy of serious investigation. In addition, hydnocarpin has antioxidant (free-radical scavenging activity) and antibacterial potential against Staphylococcus aureus (Perez 2011). Hydnocarpin derivatives, which may be present in other plant genera, have shown intriguing antibacterial potentiating activity. A number of respected medicinal herbs such as Chinese Goldthread (Coptis chinensis) contain the isoquinoline alkaloid berberine (and derivatives) – which has an excellent reputation as antimicrobial agent against bacteria, fungi and protozoal infections. Interestingly, research has shown 17 Analysis of the seed hulls has isolated the following: hydnocarpin (0.08%), methoxyhydnocarpin (0.03%), isohydnocarpin (0.03%), hydnowightin (0.05%), neohydnocarpin (0.04%). The hulls also contain flavonoids, apigenin, chrysoeriol and luteolin – as well as β-sitosterol, lupeol, β-amyrin, betulinic acid and sitosterol-β-D-glycoside (Sharma 2006).

Chinese Goldthread or Huang Lian (Coptis chinensis) is an important Chinese herb with potent antibacterial, antiinflammatory, antipyretic properties. It also has substantial sedative, tranquillising, analgesic, immune-supportive and cholagogue (increase bile secretion) attributes. Significant antimycobacterial activity has been shown by berberine bisulphate from Coptis chinensis. Golden Seal (Hydrastis canadensis) is another famous medicinal herb with an antitubercular effect that is associated with this compound.

Flavonoids have attracted particular notice as antioxidants with an ability to modify or prevent free radical damage and lipoperoxidation – thereby helping to reduce the cellular damage that accompanies ageing, cardiovascular disorders or the development of cancer (Lin 2008; Seelinger 2008a, 2008b). Luteolin has a diverse range of pharmacological properties: immunomodulatory, cardioprotective, hypotensive, antioxidant, anti-allergic, antispasmodic, antiinflammatory, anti-diabetic, hormone regulating (oestrogenic, anti-oestrogenic, anti-androgenic) and anti-mutagenic activity (Lopez-Lazaro 2009; Lin 2008; Seelinger 2008a; Kotanidou 2002; Kimata 2000).

18 Small amounts of 5’methoxyhydnocarpin have been isolated from Chaulmoogra oil from Hydnocarpus wightiana

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The Chinese medicinal herb Ya Dan Zi (the fruit of Brucea javanica), which is also fairly widespread throughout the coastal regions of northern Australia, has febrifugal, antimalarial and antidysentery properties. Extracts (twigs, leaf, inflorescence) contain quassinoids with anticancer properties (bruceantin, bruceine) – the activity of which was potentiated by the flavonolignan hydnocarpin, which is naturally present in the extract. Brucea quassinoids have diverse pharmacological properties: antiparasitic, antibabesial, anti-HIV, antimalarial, antitubercular, cancer chemopreventive and cytotoxic activities (Pan 2009).

Luteolin has interesting antimicrobial and antiparasitic potential including activiity against Chlamydia pneumoniae, Candida albicans, MRSA (methicillin-resistant Staphylococcus aureus), and antiviral properties against the influenza virus (Lopez-Lazaro 2009; Xu & Lee 2001). It has also demonstrated activity against the gonorrhoea bacteria (Neisseria gonorrhoeae) and Helicobacter pylori – the latter being implicated in the development of gastric and duodenal ulceration (Chung 2001; Tsou 2001). Antiparasitic activity against Leishmania donovani (leishmaniasis) and Plasmodium falciparum (malaria parasite) is also of interest (Mittra 2000). Luteolin has substantial potential as a dietary anticancer agent with chemopreventive and chemotherapeutic properties. Not only does it show a protective role (preventing the cellular damage associated with chemical insults that result in cancer), luteolin may be of use in treating the disease and/or be suitable for use in anticancer drug combinations (enhancing drug efficacy) – as well as having radioprotective attributes that suggest its use as a protective agent for radiotherapy. Particular interest has been expressed in a significant anticancer effect on prostate cancer cells. The fact that it can cross the blood–brain barrier also suggests possibilities for brain cancer and neurological disorders (Lopez-

Lazaro 2009; Lin 2008). In addition to protective effects against nerve damage, luteolin has potential for treating multiple sclerosis and as an anti-asthmatic agent, and may be useful for the prevention of liver fibrosis (Theoharides 2009; Lin 2008; Chiang 2003; Das 2003; Su 2003; Zhao 2002; Chowdhury 2002; Ko 2002; Kobayashi 2002; Li 2001). Other studies have indicated that luteolin has xanthine-oxidase inhibitory actions with potential for use in gout, as well as inhibitory effects on lens aldose reductase, which is involved in the development of various diabetic complications. Luteolin has also demonstrated experimental cardiovascular effects – vasodilatory, hypotensive, reduced blood flow and cardiac stimulant attributes (Kim 2011; López-Lázaro 2009; Pauff & Hille 2009; Abdalla 1994; Occhiuto & Limardi 1994). Experimentally, luteolin and apigenin have shown effects on neuropsychological chemistry (via activation of monoamine transporter activity) that may well have a beneficial influence on some emotional conditions and drug dependence (Zhao 2010).

Rooibos tea. Studies of the pharmacological properties of Rooibos tea (Aspalathus linearis) found that luteolin was an important flavonoid with significant antioxidant, antimutagenic, radioprotective and anticlastogenic properties. Certainly, it is known that flavonoids are valuable tissue-protective agents for plants, including protection against UV radiation damage (Snijman 2007; Shimoi 1996, 1994). (Image courtesy Laubrau, Free Art Licence)

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Flowering Peppermint (Mentha x piperita). Parsley, celery, carrot, green peppers, artichoke, olive oil, navel oranges and various herbs (thyme, chrysanthemum flowers, rosemary, oregano, peppermint, basil, chamomile and perilla) are among the nutritional resources that provide luteolin.

  Chaulmoogra: A New Cosmetic? There appears to be a continuing interest in the use of Chaulmoogra oil for skin disorders. For instance, a 1996 US Patent by Jacques LeClerq (Shiseido International, France) mentions its use in: ‘Dermatology, for harmonizing pigmentation of the skin’ (US Patent No. 5,5114,712). Chaulmoogra oil was incorporated into various formulations (emulsions, milks, oils, free or encapsulated forms) for face and body care products (day and night creams, beauty masks, foaming gels, sun products), hair care (shampoo, medicated creams, capillary lotions), and makeup (foundation creams). There is also a note regarding the use of Chaulmoogra oil for treating excessive fat build-up and cellulite.

Sapucainha, Carpotroche brasiliensis. (Courtesy Luis Bacher, flickr)

Sapucainha, Carpotroche brasiliensis. (Courtesy Luis Bacher, flickr)

Another patent by De Oliveira and colleagues in 2011 mentions similar cosmetic applications for Sapucainha oil or butter (Carpotroche brasiliensis) for use as a cosmetic (US Patent No. US2011/0038970 A1) via a process that ‘enables obtaining an improved product for use in cosmetic compositions instead of silicone and fatty esters compounds’. The story of Chaulmoogra oil provides a good illustration of the value of traditional remedies in the treatment of an extremely difficult disorder. Many remain sceptical about the usefulness of herbal extracts against bacterial infections and favour the exclusive use of antibiotic drugs. However, the evolution of drugresistant bacteria which are highly problematic in clinical situations has inspired a broader perspective, at least in some research fields. The integrity of the immune system can have a lot to do with disease progression and its severity. This situation is clearly evident with regard to leprosy – as well as another mycobacterial infection of growing importance, tuberculosis. The wider scope of activity of herbal medicines with immune-supportive properties

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suggests they could play an increasingly important role in the treatment of bacterial conditions. The fact that many herbs can be utilised with conventional drug therapies can only be to everyone’s benefit. Unfortunately, a general lack of appreciation of this in medical circles often hampers the use, and monitoring, of such innovations.

  Garlic as an Anti-tubercular Agent

instance, an extract of the leaf has traditionally been utilised for treating respiratory disorders such as bronchitis, bronchiectasis of the lung, asthma, pulmonary cough, whooping cough and phthisis (an old term for tuberculosis). The use of Garlic is strongly supported by experimental evidence. Garlic’s antibacterial properties have shown definite benefits against a number of bacteria responsible for respiratory infections (bronchitis and pneumonia) such as Streptococcus pneumoniae. Garlic oil has shown a profound inhibitory effect on Mycobacterium tuberculosis, comparable to conventional antitubercular drugs such as isoniazid, p-amino salicylic acid and streptomycin. It has also demonstrated activity against drug-resistant bacterial strains, as well as antifungal and anticryptococcal properties. The latter has seen the herb utilised clinically in China for the treatment of meningitis (Hannan 2011; Gupta 2010; Dikasso 2002; Jain 1998; Kapoor 1990;

Garlic, from William Woodville, Medical Botany, James Phillips, London, 1793.

Since ancient times Garlic (Allium sativum) has been used for treating respiratory tract problems. This rather remarkable herb has significant antimicrobial and immunosupportive properties and is often recommended to boost immune system function in conditions such as tuberculosis and AIDS. While the bulb has a wellestablished medicinal reputation, other parts of the plant can be utilised in a similar manner. For

Dried garlic bulbs (Xie Bai) for Chinese medicinal use as an analgesic tonic with particular value in respiratory disorders (bronchitis), pleurisy and heart problems (chest pain, angina). It also has antidiarrhoeal properties (Yeung 1985). The purpleskinned garlic has been specifically recommended for whooping cough and tuberculosis: 30 g of skinned garlic was combined with Bai-ji powder (Bletilla striata rhizome). This was added to a rice gruel and eaten following meals, with a further 4–5 cloves taken daily for 100 days (Chang 1989).

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Delaha & Garagusi 1985). Clinically, Garlic can provide relief from dyspnoea (difficulty breathing) and improve arterial oxygenation in individuals with hepatopulmonary syndrome (Abrams & Fallon 1998).

Mycobacterium tuberculosis culture. The rough colourless surface is a characteristic typical of M. tuberculosis colonial growth patterns. (Images courtesy US CDC Public Health Image Library, Dr George Kubica)

Black Garlic is a fermented form of garlic popularly used in Asian cooking. It is believed to have tonic and longevity enhancing attributes. (Image courtesy Kok Robin at www.aziatische-ingredienten.nl)

Herbal Drugs with Activity against Mycobacteria   Mycobacterial Classification Mycobacteria belong in a separate family of bacteria, the Mycobacteriaceae, in which there are several major groups. The primary ones of interest as human pathogens are those of the tuberculosis complex (M. tuberculosis, M. bovis, M. africanum and M. microti), leprosy (M. leprae, M. lepromatosis), Buruli ulcer (M. ulcerans) and AIDS-related mycobacteria (M. avium complex, M. avium paratuberculosis). There is also a rather broad category of nontuberculous mycobacteria (NTM). Numerous

non-pathogenic mycobacteria are commonly encountered in soil and water supplies and can be well tolerated by the human body. Even the tuberculosis bacteria may not cause disease (i.e. asymptomatic infection) in many individuals. However, infections with pathogenic forms of mycobacteria are notoriously difficult to treat because they possess a cellular wall structure that is highly resilient to being breached by chemicals (including detergents, antibiotics, alkali and acid compounds). In an interesting review of native New Zealand plants with anti-mycobacterial potential, Earl and coauthors provide a clear overview of the prevalence of tuberculosis (TB) infections: TB is the leading cause of death due to a single infectious organism. In 2007, 1.78 million people died from the disease and an estimated 9.27 million new cases were recorded worldwide. TB requires a lengthy treatment

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period of six months with the front-line drugs rifampicin, isoniazid, ethambutol and pyrazinamide. The availability of new drugs that shorten the course of chemotherapy would improve patient adherence and affordability, thus enabling more favourable treatment outcomes. In addition, alternative drugs are needed to counteract the spread of drug resistant TB which threatens global control programmes. MDR-TB, resistant to rifampicin and isoniazid, now exceeds 0.5 million cases per year and in some states accounts for up to 22% of TB cases. Extensively-drug resistant (XDR) strains of M. tuberculosis, resistant to both first- and second-line drugs, were first reported in the United States, Latvia and South Korea in 2006 but are now present in 57 countries (Earl 2010).

Tuberculosis has reached plague proportions in humans. In the two decades between 2000 and 2020, nearly a billion people will have become infected – with 200 million people acquiring the disease and 35 million fatalities (WHO 2000). In Australia the rate of infection is around 900–1300 cases per year, as reported between 1992 and 2011. Recent infections rates are: 1326 cases (2009), 1311 cases (2010) and 1227 cases (2011) (National Notifiable Diseases Surveillance System, April 2012). It would appear that a number of herbs with antibacterial and immunostimulant properties, some of which can be combined effectively with conventional therapies, have excellent potential for assisting in the treatment of tuberculosis. Remedies with good immunosupportive properties and a proven track record of medicinal use could well be a practical clinical blessing.   The fact that Australian brushtail possums are particularly susceptible to bovine tuberculosis (Mycobacterium bovis) has been a matter of serious concern in New Zealand. Although the condition is not present in these animals in Australia (having been eradicated in the 1970s), in New Zealand they act as an environmental reservoir of the bacteria. Around 24 per cent of the possums are infected and at risk of transmitting the disease to cattle or wild deer. The introduction of these animals has been an unmitigated disaster for the country, as they have reached plague proportions (population around 60–70 million). The infection rate in cattle can be high, which has economic consequences – albeit transmission to humans is prevented due to the milk pasteurisation process, as

Common brushtail possums (Trichosurus vulpecula). (Courtesy Bryce McQuillian, Wikimedia Common, CCby-SA 2.0)

well as direct control of the infection in cattle herds (see Exotic Possums: Tuberculosis Fact Sheet, Australian Wildlife Network 2010, www.wildlifehealth.org.au). The infection rate in other countries is equally low. In the United Kingdom, fallow deer and badgers have been identified as environmental reservoirs of the disease, with controversial badger-culling programs appearing to have very limited success. In some parts of the United States, Mycobacterium bovis is endemic in white-tailed deer – although many other animals (foxes, coyotes, pigs, rodents, domestic cats) can be carriers of the disease.

  Interesting New Zealand Natives A study by Earl (2010) that examined 45 New Zealand plant species determined that six were active against Mycobacterium smegmatis – a fastgrowing non-pathogenic mycobacterium that is useful for laboratory investigations. One of these, the Pukatea (Laurelia novae-zelandiae), has been utilised as an anti-tubercular remedy by the Maori, and has shown activity against Mycobacterium tuberculosis. A decoction of the inner bark was applied locally to tubercular lesions, chronic ulceration, skin problems and sores. In 1883 J White provided the following details of its use: ‘The bark of this tree is taken and the outer rind scraped off and steeped in water and used as a lotion for scrofula and obstinate running sores. A decoction of this bark

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… is also used as a lotion on the parts affected by venereal disease. A very strong decoction is also taken into the mouth of the sufferer and there kept for some time in case of toothache’ (in Riley 1994). Although the infusion was also taken as a remedy for syphilis and ‘sore stomach’, there may be some reservations regarding its internal use as it is an alkaloid-rich plant that is known to be toxic to small animals – albeit human poisoning is not recorded. Perhaps this is because it was not usually taken internally, although an infusion of pulped fresh bark was mentioned as a treatment for neuralgia. Studies have shown that a bark alkaloid (pukateine) has strong analgesic properties comparable to morphine. It also contains a compound known as laureline (Brooker 1993). Interestingly, there is only one other species of Laurelia (L. sempervirens) from southern Chile, and just one closely related species, Laureliopsis philippiana – plants that attest to ancient continental Gondwanan links in floral evolution. The Atherospermataceae (Southern Sassafras) family, to which these trees belong, is well represented in Australia and New Zealand. Their essential oils tend to be characterised by safrole, which accounts for their attractive aromatic qualities, albeit there are toxicological concerns with regard to this compound (see Volume 1 for further details). Although little appears to be known with regard to the phytochemistry of Laurelia novae-zelandiae, Chilean studies of Laurelia sempervirens and Laureliopsis philippiana have shown that they contain isoquinolinic alkaloids.19 The most important component of the essential oil from Laurelia sempervirens leaves is safrole (69.3%) – which was also present in Laureliopsis philippiana (2.33%), as well as cineol (14.76%). In addition, both oils contained terpenes: 3-carene (53.81% in Laureliopsis philippiana; 2% in Laurelia sempervirens) – with low levels of ɑ-phellandrene (1–3%) and ɑ-pinene (0.4–3%). While both oils exhibited fungistatic properties, the essential oil of Laureliopsis philippiana showed

the best activity over a wide range of fungi (Bittner 2009). The safrole-rich leaf and bark essential oils of Laurelia sempervirens have shown high repellence and insecticidal activity against aphids and stored grain pests such as weevils and flour beetles (Zapata 2010a, 2010b; Bittner 2008). This would suggest that chemical evaluation of the Pukatea could yield some extremely interesting results – as could studies of related Australian Atherospermataceae (formerly Monimiaceae), some species of which are known to be rich in safrole (see Volume 1).

Pukatea (Laurelia novae-zelandiae) in bushland at the Hutt River. This slow-growing tree with fragrant leaves belongs to the Southern Sassafras (Atherospermataceae) family. It can reach 35–40 metre heights in the rainforest, forming large plank-buttresses at the base for support in shallow soil or swampy conditions – and even adopts the strategy of utilising pneumatophores (specialised respiratory roots) in waterlogged soils. (Image courtesy Pseudopanax, Wikimedia Commons, Public Domain)

19 These alkaloids were derived from aporphine, noraporphine and bisbenzylisoquinolinic-type alkaloid compounds. Other studies determined asimilobine, anonaine, and norcoridine were present in Laureliopsis philippiana. Other components of interest in L. philippiana were a phenol (1,2-dimethoxy-4-(2-propenyl)-phenol: 10.58%), while Laurelia sempervirens contained ethyl cyclohexane (1-methyl-4-1-methyl ethyl cyclohexane: 18.55%) (Bittner 2009).

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Dodonaea viscosa (and a number of subspecies, including angustifolia) are found in Australia. There are also seven naturalised Conyza species.

Antimicrobial Aromatics

Pohutukawa (Metrosideros excelsa).

Other New Zealand herbs with antimycobacterial activity are the Pohutukawa (Metrosideros excelsa), pictured here in its variegated form, and Kohuhu (Pittosporum tenuiflorum). Antibacterial prospects have also been demonstrated by Ramarama (Lophomyrtus bullata), Ngaio (Myoporum laetum) and Lancewood (Pseudopanax crassifolium) (Earl 2010). Investigations have revealed that there are a considerable number of plant-based compounds with good antimycobacterial activity – and there is plenty of scope for research. The review by Earl and colleagues (2010), as well as a number of other papers20, suggest that the antibacterial potential of many plants is underappreciated. This could be of interest for Australian resources as there are many native counterparts to the species showing good activity that remain uninvestigated. Some are certainly likely to contain similar chemical components. For instance, the South African herbal remedies Conyza scabrida and Dodonaea viscosa var. angustifolia have shown anti-mycobacterial activity (Thring 2007).

Numerous highly respected medicinal herbs possess antimicrobial properties. Conventional herbal remedies that have demonstrated a high level of antimycobacterial activity include: Guaiacum (Guaiacum officinale), Hop flowers (Humulus lupulus), Jalap (Ipomoea purga), Bitter Melon (Momordica charantia), Devil’s Club (Oplopanax horridus), Buckthorn (Rhamnus cathartica), Medicinal Rhubarb (Rheum officinale), Bloodroot (Sanguinaria canadensis), Canadian Burnet (Sanguisorba officinalis), Jambul (Syzygium jambos), Canadian Yew (Taxus canadensis) and Wall Germander (Teucrium chamaedrys). There is a renewed interest in the antimicrobial properties of spices and their culinary value as antibacterial agents. Aromatic herbs of the Lamiaceae with activity against Mycobacterium tuberculosis include Sacred Basil (Ocimum sanctum), Peppermint (Mentha x piperita), Spearmint (Mentha spicata), and Lemon Balm (Melissa officinalis) (Gatuam 2007). These herbs have been traditionally valued as antibacterial and antiseptic agents for treating infectious disorders and respiratory problems – with a good reputation for efficacy for cough relief, bronchitis, asthma, and ‘consumption’ (an old term for tuberculosis). Sacred Basil has also been utilised as an antileprosy remedy (Gatuam 2007). Other traditional aromatic medicinals with good activity include Camphor (Cinnamomum camphora), Cinnamon (Cinnamomum zeylanicum), the Common Giant Fennel (Ferula communis), Juniper (Juniperus communis, J. excelsa and J. procera) and Sage (Salvia officinalis).   The Corn Mint, Mentha arvensis, is of particular interest for its antibacterial potential. Extracts have shown good activity against Chlamydia pneumoniae (now classified as Chlamydophila pneumoniae). The active components have been

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Basil, dried herb. (Courtesy Finne Boonen)

including diverse Australian marsupials (notably the koala), reptiles (lizards), amphibians (frogs), and marine life (turtles) (Salin 2011). Recent investigations of Corn Mint extracts suggest that this traditional herb has a high therapeutic value. It has demonstrated substantial anti-inflammatory and sedative properties (Salin 2011; Verma 2003); antimicrobial activity against Proteus spp. urinary tract infections (Johnson 2011); and significant gastroprotective activity (Londonkar & Poddar 2009). Mentha arvensis has also shown potentiating effects in combination with antifungal drugs (metronidazol; Santos 2012) and antibiotics (gentamicin, kanamycin and neomycin; Coutinho 2009, 2008). Corn Mint is also of interest for its activity against MRSA (methicillin-resistant Staphylococcus aureus) and drug-resistant Escherichia coli, suggesting greater scope for the therapeutic use of this herb.

Flowering Corn Mint.

identified as rosmarinic acid and the flavonoid linarin – with the latter showing significant antibacterial activity.21 Chlamydia is a major cause of respiratory tract disorders such as pneumonia, sinusitis, pharyngitis and bronchitis, as well as various inflammatory disorders (meningitis, arthritis and myocarditis). Albeit a human pathogen, Chlamydia also infects animals, 21 Linarin has been linked to the pharmacological properties of a number of other medicinal herbs. It has shown interesting antioxidant and sedative activity (Valeriana officinalis, also the flavonoid apigenin; Chow 2011; Fernandez 2004); antipyretic and anti-inflammatory properties (Buddleia cordata; Martinez-Vazquez 1998, 1996); anti-amoeba potential (Buddleia cordata; RodriquezZaragosa 1999); and neuroprotective activity of potential value for degenerative neurological disorders (Mentha arvensis and Buddleja davidii; Lou 2011; Oinonen 2006).

Mint, from Paul Hariot, Atlas colorié des plantes médicinales indigènes, Librairie des sciences naturelles, Paris 1900.

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At least 50 per cent of the Queensland Koala population suffers from Chlamydia infection – resulting in blindness, respiratory infections and female infertility. Their long-term survival prospects are further complicated by the Koala retrovirus, which is rife throughout the Koala community and suppresses the animal’s immune system. (Image courtesy www.savethekoala.com)

Elecampane (Inula helenium), from Paul Hariot, Atlas colorié des plantes médicinales indigènes, Librairie des sciences naturelles, Paris 1900. Diverse herbs from the Asteraceae are of interest as antimycobacterial agents: Chrysanthemum flower (Chrysanthemum sinense), Corn Marigold (Chrysanthemum segetum, now Glebionis segetum), Elecampane (Inula helenium), Santolina (Santolina chamaecyparissus), Atlantic Goldenrod (Solidago arguta) and Canada Goldenrod (Solidago canadensis) (Newton 2000) – and the Florist’s Chrysanthemum (Chrysanthemum morifolium) (Akihisa 2005).

Australian Antimycobacterial Candidates

Wild cottage cornfield with Asteraceae herbs such as the Corn Marigold and Corn Chamomile.

The search for antimycobacterial herbs has not involved any substantial review of the Australian flora, although there are native species with good potential. A few herbs that have been of clinical importance in Aboriginal medical traditions are certainly worthy of greater interest. The Cocky Apple (Planchonia careya) is a tree with a potent antiseptic reputation that provided a healing remedy for leprosy sores, injuries and burns (even battery-acid burns) (Levitt 1981). Recent investigations have confirmed the antibacterial potential of a number of compounds

NEW ROLES FOR OLD REMEDIES

(proanthocyanidins, triterpenes and a fatty acid) in leaf extracts, with particular activity against grampositive bacteria, including Mycobacterium smegmatis, M. fortuitum and antibiotic-resistant bacteria (MRSA, VRE) – but not Escherichia coli (McRae 2008). In the Northern Territory, traditional extraction techniques were specified for the preparation of an antiseptic remedy from this tree. A thin layer from the inside bark was stripped from the trunk, twisted and then stone-hammered to break up the fibre. The pulped mass was then soaked in water and strained. The resultant lotion was said to have excellent healing properties. The remedy was applied locally as a preventative against infection following injuries such as broken fingers or bones – while bark strips from the root could be used to secure splints. The juice from the pulped roots, which was utilised similarly, was considered particularly valuable for severe injuries such as battery-acid burns. Fire-heated leaves have been applied to circumcision and spear wounds to prevent swelling, and used for treating stonefish stings. The leaf also provided an anti-itch and antiinflammatory treatment for sandfly or mosquito bites (Barr 1993; Levitt 1981).

The Cocky Apple (Planchonia careya), fruit and flowers. Cocky Apple fruit, which is also known as the Bush Mango, has been a popular bush snack. When the fruit ripens, although it remains green-skinned, it acquires a soft consistency. The flesh is only edible when it turns from white to yellow and, although it remains somewhat stringy in character, tastes something like quince (Isaacs 1994; Levitt 1981).

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In Broome (Western Australia) the remedy had a similar reputation – the stem was plastered onto sores, or a wash made from the small fine roots (mashed and soaked in water) for itching skin problems such as prickly heat, rashes and chicken pox. The bark of the root or tree was also used to prepare a bath to cure a ‘sick person’ at Arukun, Cape York (Webb 1969). Papua New Guinea the bark infusion of a related species, Planchonia papuana, has been utilised as a stomach-ache remedy (taken daily) (Holdsworth 1993). In the Solomon Islands the macerated bark and sap were drunk as a headache cure (Perry & Metzger 1980). This species has tested positive for anti-tumour activity – with alkaloids and tannins being isolated as active components (Collins 1990).

Bottlebrush (Callistemon citrinus) has shown significant antimycobacterial activity (Frame 1998). Other herbs with similar potential are the Umbrella Wattle (Acacia ligulata, bark and leaves) and the Applebush or Fruit-salad plant (Pterocaulon sphacelatum, aerial part extract) (Meilak & Palombo 2008).

  The chemical links between species, genera and botanical families can be unexpected. For instance, the rare Peruvian plant pictured opposite, Clavija procera (Theophrastaceae family), has shown activity against Mycobacterium tuberculosis, with the triterpenoid aegicerin being identified as the active constituent (Rojas 2006). Aegicerin is also present in Embelia schimperi (Manguro 2006) and the River Mangrove, Aegiceras corniculatum (Zhang 2005) – which belong to a totally different family, the Myrsinaceae. The leaf decoction or juice of the latter was utilised by Australian Aboriginal people for the treatment of earache, which suggests it possesses analgesic properties (Lassak & McCarthy 1992).

The Black or River Mangrove (Aegiceras corniculatum), from Francisco Manuel Blanco, Flora de Filipinas, Manila, 1880–83.

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River mangrove (Aegiceras corniculatum).

Mallotus philippensis is a fairly widespread tree that ranges from Australia to Papua New Guinea, into southern China and India. It has been utilised for treating leprosy in Indian traditions as well as being recommended for bronchitis. Investigations have shown anti-tubercular activity (Gautam 2007). The fruit of this tree is the source of Kamala (a red powder prepared from the fruit hairs) that was once popular as an anthelmintic for treating tapeworm. It was considered particularly useful because it induced profuse diarrhoea, which rendered the additional use of a cathartic unnecessary.

Clavija procera, a rare Peruvian rainforest plant. (Courtesy Robbin Moran, New York Botanical Garden)

Mycobacterium fortuitum. Extracts of the Australian native herbs Eremophila alternifolia (bark and leaves) and E. longifolia (leaves) have shown anti-mycobacterial properties against both Mycobacterium smegmatis and M. fortuitum (for details see Chapter 7). (Image courtesy Janice Haney Carr, CDC

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Table 4.2 Plant Remedies with Antimycobacterial Potential that are Found in Australia (native or naturalised), and Closely Related Native Species There is a great diversity of medicinal herbs that have been used in India, China and Southeast Asia for treating respiratory disorders, tuberculosis or leprosy which rate serious interest for the treatment of mycobacterial disorders. Many have active wound-healing and analgesic properties. Some of these species have close counterparts in Australia, which suggests antibacterial potential for various native species. While the following list is not exhaustive (there are many more genera containing species with antibacterial activity), it does provide a serious indication of the antimicrobial potential of the native flora – much of which has not been chemically evaluated. This provides an indication of the vast untapped potential of the flora and the current lack of knowledge with regard to these resources. References utilised for medicinal uses (unless otherwise indicated) are: India (Gautam 2007); Australia (Lassak & McCarthy 1990); traditional Chinese medicine (TCM: Duke & Ayensu 1985). Species (extract and antimycobacterial activity: Gautam 2007) Abrus precatorius (stem) Crab’s Eye, Gidgee Gidgee Achyranthes aspera (plant extract)

Ailanthus altissima (syn A. glandulosa) (quassinoids: low level of activity) Tree of Heaven Alpinia galanga (rhizome essential oil) Galangal

Amorphophallus campanulatus (stem) Azadirachta indica (leaf) Bidens pilosa (leaf)

Brucea javanica (syn. Rhus javanica) (quassinoids, bruceoside-D, low-level inhibition)

Medicinal uses relating to potential antimycobacterial activity and additional notes Seeds toxic. Indian medicine: tuberculosis (tuberculous glands), respiratory disorders (asthma, cough, bronchitis), chest pain; roots used as substitutes for liquorice, used for treating catarrh and cough. Indian medicine: leprosy, respiratory disorders (bronchitis, cough, asthma, lung infections) utilised as an expectorant, skin disorders. TCM: decoction for bleeding; tincture in wine for internal injuries; analgesic. Indian medicine: asthma. TCM: leaf and stembark used for treating lung ailments; extracts bactericidal; antidysenteric. Australia: A. triphysa resin used for treating ulcers. Indian medicine: tuberculous glands, chest pain, respiratory disorders (bronchitis), sore throat, expectorant action. TCM: root used for gastrointestinal distress; antiperiodic (fevers). Indian medicine: leprosy, respiratory disorders (asthma, bronchitis, lung disorders etc.), fevers. Indian medicine: respiratory disorders (asthma, cough, phthisis, tuberculosis); leprosy. Indian medicine: pulmonary disorders, leprosy. TCM: leaf decoction anti-inflammatory and styptic, used for lung trouble; anti-inflammatory; antirheumatic; juice for treating wounds and ulcers. India, TCM: Widely utilised for treating feverish conditions and dysentery. Australia: leaves and roots used as analgesic in north Qld.

Distribution in Australia (native species) or status (naturalised/cultivated); and Australian relatives (species) Distribution: northern Qld, NT.

Distribution: WA, NT, NSW, coastal islands. Australian species: A. arborescens, A. margaretarum.

Naturalised: WA, SA, Qld, NSW, ACT, Vic. Australian species: A. integrifolia, A. triphysa. Cultivated Australian species: A. arctiflora, A. arundelliana, A. caerulea, A. hylandii, A. modesta; A. racemigera (= Pleuranthodium racemigerum). Australian species: A. paeoniifolius (syn. A. campanulatus); A. galbra. Cultivated and naturalised: NT, WA, Qld. (Melia azedarach is a closely related native species.) Distribution: east coast of Australia, SA, some islands. Additional Australian species: B. bipinnata, B. subalternans, B. tripartita. Distribution: WA, NT, Qld.

NEW ROLES FOR OLD REMEDIES Caesalpinia pulcherrima (root)

Cannabis sativa (unspecified) Canscora decussata (xanthones incl. mangiferin; total xanthones had activity comparable to streptomycin) Capsella bursa-pastoris (whole plant) Shepherd’s Purse Carica papaya (leaf) Pawpaw tree Casuarina equisetifolia (seed, leaf, stem: good levels of inhibition) Catharanthus roseus (aerial parts) Madagascar Periwinkle Cinnamomum camphora (unspecified) Camphor Tree, Camphor Laurel

Cissampelos pareira (leaf, stem: good level of inhibition) Citrullus colocynthis

Clausena excavata (coumarins)

Convolvulus arvensis (leaf)

Indian medicine: Used to treat patients with tuberculosis symptoms, bronchitis, asthma; seeds tonic and febrifuge (intermittent fevers). Other species with positive antimycobacterial activity: C. sappan also used for leprosy and asthma. C. digyna for tuberculosis (glandular, intestinal and bovine). Indian medicine: leprosy and bronchitis. TCM: seed used to treat wounds and ulcers; analgesic, antibacterial. Indian medicine: leprosy and tuberculosis.

Naturalised: Christmas I. Numerous native species: C. bonduc, C. crista, C. erythrocarpa, C. hymenocarpa, C. major, C. nitens, C. robusta, C. subtropica, C. traceyi.

Indian medicine: chest complaints; general infectious disorders, antiseptic, disinfectant. TCM: leaf ashes for fluxes, pulverised for application to sores; antidiarrhoeal. Indian medicine: expectorant. TCM and various traditions: widely used for growths and cancers; leaves for nervous pains; leaf smoked for asthma relief; latex used for wound healing. Indian medicine: diarrhoea, dysentery, stomach-ache. Australia: bark astringent for diarrhoea.

Naturalised throughout the Australian continent.

Indian medicine: cancer, antidiabetic, tonic.

India: C. camphora utilised for leprosy. India: C. zeylanicum employed for the treatment of bronchitis and has an expectorant action (leaf extract gave complete inhibition of bacteria). TCM: plant used as antiarthritic; traumatic injury; antiseptic; tumours and cancerous ulcers. Australia: C. oliveri astringent bark, tincture used for diarrhoea and dysentery. India: leprosy, tuberculosis, respiratory disorders (asthma, cough, bronchitis). TCM: root antirheumatic. India: leprosy; tuberculous glands of the neck, respiratory disorders (asthma, bronchitis).

India: fever, indigestion, malaria, colic, muscular pain, diuretic, tonic. Thai medicine: treatment of colds. TCM: leaf poultice (with other herbs) or stem bark fumigation used for ulcerated nose. India: fevers; purgative, cathartic activity. Many species have been utilised as purgative and wound healing agents. Australia: C. erubescens plant decoction used for gastrointestinal disorders (diarrhoea, indigestion, stomach pain).

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Naturalised: WA, NT, SA, Qld, NSW, Vic (widely cultivated). Australian relatives: C. diffusa: WA, NT, Qld.

Naturalised: NT, Qld and some northern islands.

Distribution: WA, NT, Qld, NSW. Other native species: C. cristata, C. cunninghamiana, C. glauca, C. obesa, C. pauper. Naturalised throughout country (except Vic and Tas). C. camphora naturalised: WA, Qld, NSW, Vic, Norfolk I, Lord Howe I. Native Australian species: C. baileyanum, C. iners, C. laubatii, C. oliveri, C. propinquum, C. virens.

Distribution: Qld.

Naturalised throughout continental Australia (not found in Tas). Related species: C. lanatus (syn. C. vulgaris) (naturalised, same distribution). Naturalised: Christmas I (as well as C. lansium). Native species: C. brevistyla, C. smyrelliana plus Clausena sp. Tipperary. Naturalised: Qld. Numerous native species: C. angustissimus, C. clementii, C. crispifolius, C. erubescens, C. eyreanus, C. graminetinus, C. microcephalus, C. recurvatus, C. remotus, C. tedmoorei, C. wimmerensis. (Note many closely related species are also classified in the genus Ipomoea).

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Conyza aegyptiaca (leaf)

India: skin diseases.

Cucurbita maxima (fruit) Cucurbita pepo (fruit) Curcuma domestica (syn. C. longa) (leaf) Drymaria cordata (whole plant) Eclipta alba (aerial parts) Elephantopus scaber (whole plant)

India: diuretic, tonic, analgesic; used in treatment of inflammation, migraine, boils, neuralgia. India: leprosy and bronchitis.

Erythrina variegata var. orientalis (syn. E. indica) (root bark)

Eugenia uniflora (leaf)

C. longa naturalised: Qld. Native species: C. australasica.

India: respiratory disorders (asthma), coughing and colds. India: leprosy, respiratory disorders (asthma, bronchitis); expectorant. India: respiratory disorders (bronchitis, cough), colds. TCM: root antidiarrhoeal and for gastroenteritis, tumours, chest pain; plant antibacterial (gonorrhoea), abscesses, influenza, pharyngitis. India: cough, microbial infections. TCM: leaf antibacterial (anti-syphilis); bark analgesic in arthritis, neuralgia, rheumatism, febrifuge, expectorant; leaf juice antibacterial and analgesic (earache, toothache). Australia: E. vespertilio: leaf decoction sedative; infusion of bast and bark used for sore eyes and headache. India: skin infections, microbial infections.

Naturalised: Qld, NSW.

India: at least 23 species are used medicinally. Australia: latex or milky juice from this weed (as well as other species) used as a wart removal agent.

Hibiscus trionum (leaf)

India: skin diseases, itching (pruritus), diuretic, stomach-ache. Australia: H. tiliaceus: inner bark and sapwood heated infusion used as antiseptic; H. vitifolius tuber used for treatment of boils. India: expectorant, chronic catarrh of lungs, cough, wound healing (antiseptic and disinfectant).

Luffa cylindrica (aerial parts)

Lygodium japonicum (whole plant)

Naturalised: WA, SA, Qld.

India: leprosy and bronchitis.

Euphorbia peplus (leaf, stem)

Hypericum perforatum (leaf, whole plant, aerial parts, flowers) St John’s Wort

Naturalised in Qld. Other naturalised species are widespread across the continent: C. bilbaoana, C. bonariensis, C. canadensis, C. leucantha, C. primulifolia, C. sumatrensis. Naturalised: Qld, NSW.

India: leprosy, bronchitis, expectorant TCM: leaf and fruit for inflammation, antibacterial – crushed leaf for abscesses, carbuncles, heat rash, swellings; fruit ash mixed with vermillion for smallpox pustules. TCM: spores used as diuretic and for treating urinary tract stones. Antibacterial properties (Yeung 1985).

Native species: E. alatocarpa, E. platyglossa, E. prostrata. Distribution: northern regions (NT, Qld). Native species: E. spicatus (same distribution). Naturalised: E. mollis (NSW, Qld). E. variegata: Qld coast, also in NT. Native species: E. fusca, E. insularis, E. lysistemon, E. numerosa, E. vespertilio. Naturalised: E. crista-galli.

Naturalised: Qld, NSW, Norfolk I. E. brasiliensis: naturalised (Qld). Native species: E. reinwardtiana (WA, Qld coast). Naturalised throughout the southern part of the continent (ranges from WA to SA, southern Qld, NSW, inland Vic and throughout Tas). There are numerous native and naturalised Euphorbia species (around 70, including a number that have not been botanically categorised). Distribution: found throughout the continent (including Tas). Around 50 species found in Australia, the majority are native. Naturalised: 19 species are found in Australia, many are naturalised; H. perforatum is the most widespread, found throughout the continent (including Tas). Native species: H. gramineum, H. japonicum (not NT), H. pusillum (Tas only). Native species: L. aegyptiaca (syn L. cylindrica) WA, NT, Qld; L. graveolens (WA, NT).

Naturalised NT, Qld, NSW. Native species: L. flexuosum, L. microphyllum, L. reticulatum.

NEW ROLES FOR OLD REMEDIES Mallotus philippinensis (bark) Kamala Tree

India: leprosy, bronchitis. TCM: fruit bactericidal; used for treating colds, skin disorders, ringworm, scabies, herpes, tumours. Australia: M. mollissimus milky sap with coconut juice as dysentery cure.

Mangifera indica (leaf)

India: respiratory disorders (asthma, bronchitis, cough, throat troubles). TCM: Leaf ashes for burns and scalds, burning leaf smoke inhalant for respiratory disorders (asthma, cough) and skin problems; bactericidal and fungicidal. India: expectorant, bronchitis. TCM: oil inhalant for colds, coughs, rhinitis; oil drop on sugar for cholera, colic, anodyne, antiseptic. Australia: extensive medicinal uses; wide use as antiseptic agent (see also Volume 2). India: leprosy, asthma.

Melaleuca leucadendron (essential oil)

Mimosa pudica (leaf) Momordica charantia (leaf)

India: leprosy, respiratory tract (asthma, bronchitis, expectorant). TCM: antidiabetic.

Morinda citrifolia (leaf)

India: tuberculosis, respiratory disorders. Australia: rootbark infusion antiseptic.

Passiflora foetida (stem) Stinking Passionfruit

India: asthma.

Physalis angulata (aerial parts)

India: gastric disorders, diuretic, earache, tumours.

Plantago lanceolata (leaf, root, flowers, sap)

India: respiratory disorders (cough, pulmonary diseases; expectorant).

Plantago major (whole plant; leaf) Plantago

India: leprosy.

asthma,

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Distribution: NT, Qld, NSW. Additional native species: M. claoxyloides, M. discolor, M. dispersus, M. ficifolius, M. megadontus, M. mollissimus, M. nesophilus, M. paniculatus, M. polyadenos, M. repandus, M. resinosus, M. surculosus. Naturalised: WA, NT, Christmas I, Qld, NSW. M. odorata naturalised (Christmas I).

= M. leucadendra: native to Qld, NT, WA. Around 269 Melaleuca species are found in Australia (some of which may be reclassified at Callistemon at a later date). Naturalised: NT, Qld, NSW, Christmas I. Naturalised: M. diplotricha (Qld), M. invisa (Christmas I), M. pigra (NT, Qld). Distribution: Qld, Christmas I. Naturalised: NSW. Additional native species: M. balsamina, M. cochinchinensis. Distribution: coastal Qld, NT, WA and nearby islands. Additional native species: M. acutifolia, M. ammitia, M. bracteata, M. canthoides, M. constipata, M. jasminoides, M. podistra, M. reticulata, M. retropila, M. salomonensis (now Coelospermum paniculata var. syncarpum), M. umbellata. Naturalised: WA, NT, Qld, NSW, Christmas I, Cocos (Keeling) Is. Numerous naturalised species: P. caerulea, P. coccinea, P. edulis, P. filamentosa, P. laurifolia, P. maliformis, P. morifolia, P. quadrangularis, P. sanguinolenta, P. suberosa, P. subpeltata, P. tarminiana. Native species: P. aurantia, P. aurantioides, P. cinnabarina, P. herbertiana, P. kuranda. P. angulata (‘Native Gooseberry’) may be pre-European introduction in NT. Otherwise considered naturalised throughout the country. Naturalised: P. alkekengi, P. cinerascens, P. crassifolia, P. hederifolia, P. ixiocarpa, P. lanceifolia, P. longifolia, P. micrantha, P. minima, P. peruviana, P. philadelphica, P. pubescens. Naturalised: NSW, Vic, SA, WA, Qld, Tas (not NT). Numerous species (around 37) found across the continent; the majority are native. Naturalised: NSW, Vic, SA, WA, Qld, Tas (not NT).

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Portulaca oleracea (leaf)

India: leprosy, asthma, cough. Australia: nutritive and blood-cleansing attributes; mild diuretic; antiscorbutic.

Prunus domestica (leaf) Prunus persica (stem)

India: digestive disorders (aperient), laxative, gynaecology (irregular menses, leucorrhoea). India: respiratory disorders (cough, bronchitis, expectorant). TCM: leaf febrifugal for cholera and typhoid; kernel used as antitussive agent, antibacterial for carbuncles, febrifuge for ague, cough. India: cough. TCM: leaf, flower and fruit antibacterial; fruit extract anti-Salmonella; antidiabetic agent.

Psidium guajava (stem) Guava Punica granatum (whole plant) Pomegranate

Ricinus communis (whole plant) Castor Oil plant

Rubus fruticosus (aerial parts) Raspberry

India: respiratory disorders (bronchitis, cough, sore throat, chesty troubles). TCM: antidysenteric agent; anthelmintic; antibacterial, antiparasitic, astringent, antiviral (Yeung 1985). India: leprosy, asthma, bronchitis. TCM: leaf and root decoction antiarthritic, antitussive and expectorant, facial palsy; heated leaves to treat gout and swellings; powdered seed antibacterial (abscesses, boils, carbuncles, other skin disorders). India: wound-healing, antiseptic and disinfectant qualities; whooping cough.

Salix alba (unspecified)

India: diarrhoea, dysentery (astringent), rheumatism, tonic.

Sida acuta (leaf)

India: gastric disorders and stomach-ache, back pain, boils, burns, tonic; fever, nervous problems, urinary tract disorders. TCM: leaf decoction for influenza; plant to treat boils, cough, cuts, fevers antibacterial (gonorrhoea); antirheumatic. India: respiratory problems (cough, phthisis, throat diseases). TCM: plant used to treat bruising and swellings; widely used elsewhere for respiratory disorders (cough, asthma), fevers, paralysis (hemiplegia), inflammation; sores, ulcers, antirheumatic; antidysenteric. Australia: S. rhombifolia (syn. S. retusa) plant eaten for indigestion, root decoction for diarrhoea; Europe: used for tuberculosis and as antirheumatic.

Sida cordifolia (unspecified)

Distribution: throughout Australia. Total of 22 native species: P. australis, P. bicolor, P. clavigera, P. conspicua, P. decipiens, P. digyna, P. filifolia, P. intraterranea, P. napiformis, P. oligosperma, P. pilosa, P. tuberosa (plus a number of unnamed spp.). Naturalised: P. grandiflora. Cultivated and naturalised: SA, NSW, Vic, Tas. Cultivated and naturalised: WA, SA, Qld, NSW, Vic, Lord Howe I.

Cultivated and naturalised; Qld, NSW, Lord Howe I, Christmas I, Norfolk I. P. cattleyanum and P. guineense also naturalised. Cultivated and naturalised: SA, Qld, Lord Howe I.

Naturalised across the continent and islands (not Tas).

Naturalised: a surprising number of other species have been naturalised across the continent. Total number of species: 38. Native species: R. fraxinifolius, R. gunnianus, R. moluccanus, R. moorei, R. nebulosus, R. niveus, R. parvifolius, R. probus, R. pyramidalis, R. queenslandicus, R. radula, R. rosifolius. Cultivated and naturalised SA, NSW, Vic, ACT. A number of other Salix species (total 16 spp.) and numerous hybrids are also naturalised. Naturalised: WA, NT, Qld, NSW, Christmas I and the Cocos (Keeling) Is. Numerous species (total 39 spp.) are found across the continent; the majority are native.

Qld, NT, WA.

NEW ROLES FOR OLD REMEDIES Solanum dulcamara (leaf, whole plant) Bittersweet

Solanum tuberosum (leaf) Potato plant Stellaria media (leaf, whole plant) Chickweed

India: leprosy; respiratory disorders (chronic bronchial catarrh, asthma, whooping cough). TCM: stem antiarthritic, anti-asthmatic, whooping cough; vinegar-marinated berries applied to cancerous sores and swellings. India: cough.

Naturalised: Tas. There are numerous native and naturalised species (total 186 spp.) See Chapter 12.

India: bone fractures, sprains, astringent. TCM and elsewhere: widely used for skin disorders (eczema, psoriasis, sores, ulcers, swellings, warts); wounds; anticancer (tumours); febrifuge; antirheumatic (analgesic).

Naturalised throughout the continent (incl Tas) and islands. Native species: S. angustifolia, S. caespitosa, S. filiformis, S. flaccida, S. glauca, S. multiflora, S. parviflora, S. pungens. Naturalised: S. graminea, S. pallid. Cultivated and naturalised in Qld. There are numerous native species of Syzygium (around 76, including a number of naturalised species). Naturalised: NSW, Qld. Also naturalised: T. patula.

Syzygium jambos (= Eugenia jambos) (leaf) Jambu Tagetes minuta (aerial parts) Stinking Roger Taraxacum officinale (leaf) Dandelion

India: cancer, colic, diabetes, diarrhoea, dysentery, tonic.

Terminalia catappa (stem) Beach Almond Typha latifolia (leaf) Vigna marina (= V. lutea) (aerial parts)

India: leprosy and bronchitis. Australia and Oceania: extensive medicinal uses (see also Volume 2). TCM: leaf used as vulnerary (healing agent); flower analgesic (menstrual disorders), anti-inflammatory. Australia: V. vexillata roots chewed and eaten for constipation.

Xanthium strumarium (whole plant, aerial parts)

India: cancer, wounds, malaria, headache, ulcers, rheumatism. Elsewhere (Duke & Ayensu 1985): antibacterial (syphilis, skin infections), skin disorders (abscess, boils), febrifuge, smallpox, infections, respiratory disease (asthma, colds, sinusitis, rhitinitis); analgesic, antiarthritic, anti-herpes (shingles), tumours, wounds. India: respiratory disorders (cough, asthma).

Zizyphus mauritiana (root)

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India: wound-healing, bronchodilatory activity.

antiseptic,

disinfectant;

India: phthisis (TB). Europe: used as a liver tonic and diuretic remedy.

Cultivated and naturalised: WA (southeast), NSW, Vic, SA.

Naturalised. Also naturalised: T. hepaticolor, T. koksaghyz, T. khatoonae, T. squamulosum. Native species: T. aristum, T. cygnorum. Distribution: tropical Qld and NT. There are numerous native species of Terminalia (around 30 spp.) Naturalised: NSW, Tas. Native species: T. domingensis, T. orientalis. Distribution: coastal NSW, Qld, NT. Native species: V. angularis, V. canescens, V. hosei, V. lanceolata, V. luteola, V. radiata, V. suberecta, V. unguiculata, V. vexillata (plus a number of unnamed and naturalised spp.). Naturalised: throughout the continent (not Tas). X. spinosum is also found naturalised in Australia.

Distribution: Qld, NT. Native species: Z. oenopolia, Z. quadrilocularis.

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A stand of tropical eucalypts.

  The Eucalypt has long been valued for the treatment of respiratory disorders, including tuberculosis. Indeed, the Eucalypt is one of the most popular remedies for the treatment of tuberculosis in Uganda (Tabuti 2010). This is probably largely due to the decongestant, antispasmodic and antibacterial effects of 1,8-cineole. However, studies of Eucalyptus botryoides, E. camaldulensis, E. citriodora, E. deglupta, E. globulus, E. grandis, E. maculata and E. tereticornis have shown only very weak antimycobacterial properties (Newton 2000). Some Eucalypts do contain oleanic and ursolic acids, which have a broad spectrum of anti-mycobacterial activity (Bamuamba 2008). They include the Forest Red Gum (E. tereticornis), Blue Gum (E. globulus) and the River Red Gum (E. camaldulensis subsp. obtusa). Ursolic acid has also been found in Tea Tree (Melaleuca leucadendra) extracts (Chen 2002; Siddiqui 2000; Patnaik 1991). Therefore, some species may be more useful than others as antimycobacterial agents. It is equally likely that different types of preparation and extraction procedures would influence their antibacterial potential.

Eucalyptus globulus, from RG Baker & HG Smith, A Research on Eucalypts, Technical Museum, Sydney, 1920.

 The age-old reputation of many plant products as antibacterial or wound-healing agents is obviously well deserved. Even Cannabis, a herb that is under intense cultivation in many parts of Australia, has significant antibacterial properties. However, there is a diverse array of other natural products with equally interesting potential. It may come as a surprise to find that the most potent, and medicinally valuable, antibacterial agents were sourced from common old earth. Mud poultices have been a traditional wouldhealing remedy since ancient times across the globe, as were mouldy fruits and grains – and with good reason. Investigations were to find that various soilderived fungi rated highly as antimicrobial resources. Indeed, over time, the search for antibacterial agents has evaluated an inconceivable range of soil microorganisms, fungi and fruit-derived moulds. The results have been spectacular, providing the foundation for the practice of medicine as we know it today.

NEW ROLES FOR OLD REMEDIES

 Cannabis: An Ancient Antibacterial Agent

Cannabis seeds and leaf.

Cannabis leaves. (Courtesy Farmer Dodds, flickr)

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have Historically, Marijuana has been widely used as a potent analgesic, antibacterial and anti-inflammatory remedy. Over the centuries, these effects would have influenced the practical use of cannabis in folk medicine. Certainly, it is effective for the treatment of a vast array of conditions, including its use as an analgesic in cancer. Research has substantiated many traditional recommendations, mainly (but not exclusively) linking the effects of Cannabis to its cannabinoid components.22 Cannabidiol has attracted particular interest as an anticancer agent (Appendino 2011). A number of cannabinoids have significant anti-infective properties. For instance, THC (tetrahydrocannabinol) has demonstrated inhibitory anti-viral activity against Herpes simplex, even at low doses (Blevins & Dumic 1980). Cannabidiol, cannabigerol, cannabidiolic acid and cannabigerolic acid have shown antibiotic properties (ElSohly 1982). A 1960 report stated: ‘Noteworthy is the effect upon Staphylococcus aureus strains which are resistant to penicillin and to other antibiotics … That was one of the peculiar properties of cannabis which was found to be most attractive. We saw the possibility of using the antibiotic action locally, without any danger of producing resistant strains to other antibiotics administered at the same time throughout the treatment’ (Kabelik 1960). It proved effective against the causative agent of tuberculosis (Mycobacterium tuberculosis) – as well as a wide range of pathogenic bacteria (Staphylococcus, Streptococcus, Enterococcus, Corynebacterium and Bacillus). Resin extracts inhibited Mycobacterium tuberculosis down to a dilution of 1:150,000 – as well as having a remarkable inhibition of S. aureus haemolyticus, even at 1:1,000,000 dilution (Kabelik 1960). Experimentally, the 22 Over 500 different compounds have been isolated from Cannabis sativa – around 100 of which are cannabinoids, while another 120 are terpenoid-based. In addition, polyketides, modified sugars, alkaloids, flavonoids, stilbenoids and quinones are present (Appendino 2011). Cannabinoids (cannabigerol and its acid) have also been isolated from the African herb Helichrysum umbraculigerum, with related compounds being found in the New Zealand liverwort Radula marginata – although little is known about their phytochemistry (Appendino 2011).

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main cannabinoids (THC, cannabidiol, cannabinol, cannabichromene, cannabigerol) have shown good activity against drugresistant Staphylococcus aureus (MRSA). Cannabinoids (THC, cannabidiol, cannabinol) also possess significant anti-inflammatory properties (Appendino 2011). Indeed, THC has demonstrated activity twenty times more potent than aspirin and twice that of cortisone (Formukong 1989). Current research has focused on the development of drugs for the treatment of nausea and anorexia (particularly that associated with chemotherapy), conditions associated with pain and inflammation, insomnia, glaucoma, and spasticity from spinal injury. Some cannabinoids also have neuroprotective properties that may be of clinical value. THC has been proposed as a neuroprotective agent

in Parkinson’s disease, while some cannabidiol analogues may have a protective role against optic nerve damage (Appendino 2011). Indeed, experimentally THC and cannabidiol can both enhance the penetration of various drugs into the brain (Reid & Bornheim 2001). Cannabidiol can help with pain relief and spasticity in the treatment of conditions such as multiple sclerosis and amyotrophic lateral sclerosis (Appendino 2011). This is of interest as morphine and THC have very similar pharmacological properties, despite a different mechanism of action (Rapaka & Sorer 1994). Therefore it is not too surprising to find that a recent clinical study of the treatment of pain with opioids and inhaled cannabis suggests that this combination had a significant enhanced analgesic effect – which may well help address the problems with opiate addiction and tolerance in individuals on long-term drug therapy (Abrams 2011).

Chapter 5

EARTH MEDICINE: A MINERAL PHARMACY Numerous seemingly improbable remedies have been used by ancient cultures – some of which involved odd practices. Despite sounding somewhat farfetched, quite a few were ultimately shown to contain an element of truth. The search for antibacterial agents involved experimentation with various unusual remedies – and their exposure to the scrutiny of modern chemical studies has revealed some rather surprising results. In ancient cultures, commonly available items such as beer and honey were popular antibacterial remedies that were found helpful for the treatment of abscesses, sores and boils (Nunn 1996). The yeast in beer sediment is rich in vitamin B and contains antimicrobial components – properties that tend to support its use in intestinal complaints and skin diseases.

Physicians in many cultures had long observed that mould could be used as a wound-healing agent. Mouldy bread was deployed in many folk-healing traditions, including that of Ancient Egypt, where it was recommended for treating blisters, intestinal disorders and pus-forming wounds. In 1908, Dr AE Cliffe, a Canadian biochemist touring in central Europe, noted: ‘I came across the fact that almost every farmhouse followed the practice of keeping a mouldy loaf on one of the beams in the kitchen. When I asked the reason … I was told that this was an old custom and that when any member of the family received an injury such as a cut or bruise, a thin slice from the outside of the loaf was cut off, mixed into paste with water, and applied as a bandage. It was assumed that no infection would result from such a cut’ (Lechevalier & Solotorovsky 1965). Much later it was established that the characteristic blue-green discoloration seen on mouldy bread was the useful antibiotic-producing Penicillium mould. Across the world, other antibacterial folk remedies have included mouldy jam (Canada), chewed apple or barley allowed to grow mould (central Asia), mouldy corn soaked in water or date wine (Jewish traditions), mould scraped from cheese (Ancient Greece), and mouldy soya bean paste (China). King James I’s personal herbalist, John Parkington, advocated the use of mould in 1640 in his Theatrum Botanicum. Other English traditions tell of the use of mouldy porridge, wheat straw and oranges, rotten apples, green leather (old boots), and mouldy ham and/or bacon fat (Wainwright 1989a, 1989b; Bickel 1971; Kavaler 1962). All these recommendations exploited the mould’s natural antibacterial principles. A letter to Professor of Biology Milton Wainwright (1989b) from a Mr D McCarthy of Hull (County Cork, Ireland) recounted:

The Ebers Papyrus (around 1550 BC), discovered in 1873–74 by George Ebers, is among the most important medical texts of the Ancient Egyptians. (Courtesy Einsamer Schütze, Wikimedia Commons, CC-by-SA3.0 Unported)

Many years ago an old aunt of mine (who was some 82 193

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years old), who appeared to be quite learned in ‘cures’, read one day in a magazine of Professor Fleming’s discovery of penicillin which was described as result from research on a mould. My aunt said in her own inimitable way ‘I had that cure before he had!’ I know that one of her cures was to collect ten to twelve oranges and place them somewhere they would get mouldy as soon as possible. She would then carefully remove the greenish mould and make it into some form of concoction/defusion/infusion and use it on abscesses, whitlows, boils, or other forms of pustule. She would also administer it orally, and all apparently with complete success. Mouldy oranges once provided a household antibiotic remedy for all types of wounds and infections.

A similar remedy was used by the grandfather of Mrs L Collingwood (also of Hull, Ireland) in the 1920s: ‘If we had nasty sore knees, grit and scabs from falling down, he used to get his penknife and cut and scrape the ham or bacon side hung from the ceiling (to be cured), salted and green and put the fat on a piece of clean linen and grandma used to wrap our knees up and it always cleansed and healed our wounds.’ Aboriginal healers used moulds sourced from the sheltered side of Eucalypt trees to treat wounds (Kavaler 1967). Certainly, Australian bushmen knew of this practice, with one travelling to Melbourne to give the Walter and Eliza Hall Medical Institute1 ‘a smelly bundle of moulds wrapped in sacking’, with the suggestion that they should be investigated because ‘they appeared to defeat infection and promote healing’ (Wainwright 1989b; Bickel 1972). An interesting case history of the 1920s regarding a treatment for impetigo (a skin disease due to Staphylococcus aureus) mentioned the use of a mouldy starch-impregnated face mask and wraps on affected areas. In Sheffield (England), a Dr Twomey recommended the use of a starch mix that had been allowed to turn mouldy: ‘On his return Twomey found, as he had expected, that the surface of the starch was covered with a luxuriant growth of green mould. Next, he told Brenda’s mother to scrape out 1 This was the first medical research institute established in Australia, opened in 1915 by Eliza, widow of Walter Hall, a rich transport, livestock and mining entrepreneur.

the mouldy starch and apply it to a mask placed over the young girl’s face so that the mould was in close contact with the infection’ (Wainwright 1989a). It took a month for the infection to clear, when the young patient was allowed to return to school. An investigation of this treatment by Wainwright in 1989 commented: ‘A hot-water, domestic starch (obtained from Boots, the Chemist) provided ideal, apparently selectively isolate species of Penicillium and Aspergillus. When a sample of starch contaminated with the former fungus was tested against Staphylococcus aureus on nutrient agar it formed a small inhibition zone, showing that it was producing an antibacterial agent.’





Ancient Antibiotics from Beer

Wooden model of beer making in ancient Egypt, located at the Rosicrucian Egyptian Museum in San Jose, California. (Courtesy E Michael Smith CC-bySA 3.0 Unported)

The ancients not only appreciated beerdrinking as a pleasurable convivial pastime, but the beverage was considered to have significant medicinal qualities. In Ancient Egypt it provided remedies that ranged from wound dressings and mouthwashes (to treat the gums), to enemas or a vaginal douche. The dried remains of the grain left over from the brewing process were even deployed as a fumigant (burned to produce smoke) to treat anal disorders (Armelagos 2000). Sycamore figs were often fermented in ‘sweet beer’ for treating intestinal distress, urine retention, or used as a cough remedy. Onion, which was considered an essential remedy for treating snake bite, was finely ground in beer, masticated and spat onto the injury site. Another emetic recipe for the same purpose included onion, natron and sweet

EARTH MEDICINE: A MINERAL PHARMACY

beer (or a suitable fermented liquid) (Nunn 1996). The naturally fermented beer contained antibiotic substances. In the 1980s bone samples from a Nubian mummy were shown to contain the antibiotic tetracycline – indicating constant exposure over the four months that it would take for the bone cells to develop. Subsequent investigation of human remains from Egypt (Roman period) and Jordan (2nd century BC – 4th century AD) gave similar results. The antibiotic, which would have been incorporated into the diet, appears to have been in the beer. It would have been naturally formed due to fortuitous contamination by a streptomycete fungus (probably genus Streptomyces), during the traditional brewing process. As part of this process, bread dough was ‘set out’ to naturally acquire an airborne yeast, then partially baked, which allowed the yeast within to continue growing. Finally, it was added to a broth of malted grain to undergo fermentation. Under the right conditions the beer would become a significant antibiotic resource.

Antibiotics: The Dirt on Microorganisms

Lister’s chemical cabinet. This chemistry set was said to have been used by Joseph Lister at Glasgow when he was in residence during 1860–69 as Professor of Surgery. During this time he pioneered the concept of antiseptic surgery using carbolic acid. The chemical set, which was acquired by Henry Wellcome when the Male Surgical Ward at the Royal Glasgow Infirmary was demolished in 1928, is now housed at The Wellcome Collections, Science Museum, London.

  A Brief Look at Antibiotic Discovery

Although many types of yeast are suitable for baking and brewing purposes, Saccharomyces cerevisiae (pictured) is the main species that has been instrumental to these endeavours since ancient times. (Image courtesy Masur, Wikimedia Commons)

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Penicillium chrysogenum (formerly P. notatum) mould produces conidia (spore chains) from brush-shaped conidiophores. (Courtesy Crulina98, Wikimedia Commons, CC-by-SA 3.0 Unported)

The latter part of the 1800s saw science take a serious interest in penicillin-based moulds that

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were observed to possess effective antibacterial properties. In 1870 the fact that mould could inhibit bacteria in culture fluid was mentioned by Sir John Scott Burdon-Sanderson, a lecturer at St Mary’s Hospital in London. A few years later, in 1874–75, William Roberts and John Tyndall demonstrated antibacterial effects of a mould called Penicillium. In the late 1870s the French scientists Louis Pasteur and Jules François Joubert found anthrax bacilli were inhibited by mould exposure. A decade afterward, in 1887, the French scientist Garré reported similar findings.  Importantly, Ernest Duchesne, at the Imperial School of Military Medical Service in Lyon, wrote a paper in 1897 on the fact that Penicillium glaucum (an imprecise identification of the time that was applied to a number of moulds) healed typhoid infection in guinea pigs. He was inspired by Arab stable boys’ use of mould-based applications for healing sores on horses’ legs. However, the article was largely ignored by the medical community. Other researchers in Belgium (Gratia & Dath 1920) and Costa Rica (Twight 1923) demonstrated that species of Penicillium, in particular, had antibiotic effects. Their work was similarly dismissed. A little later, in 1928, the Scottish biologist Alexander Fleming was to reveal the specific value of Penicillium notatum – although it was over a decade before he could convince any chemist to take the idea seriously enough to develop a stable form of the drug. The discovery was pure chance, as not all strains of this bacterium produce penicillin, and few produce it in any great quantity. It was a highly fortunate set of circumstances that resulted in the right mould, with a suitable form of substrate, and the right conditions for incubation, occurring together. It was even more fortunate that Fleming didn’t overlook the fact that one of his bacterial tests had not grown Staphylococcus bacteria. He proceeded to validate the mould’s antibacterial activity with the help of Ronald Hare. Later, the research skills of Howard Florey and his team, notably Ernest Chain and

Norman Heatley, were essential in bringing penicillin production into reality in 1938. It was enterprising research in the United States during 1941–44 that turned production into a viable commercial venture, initiating the supply of large quantities of pharmaceutical-grade material. It was a tortuous road to achieving the provision of effective antibacterial drugs for practical clinical use. Early attempts at producing penicillin employed old dairy equipment, and then hospital bedpans, for growing the mould. The collection process merely involved straining the liquid underneath the mould through parachute silk. Later, Florey went to the United States to search for better production methods, and a thick liquid by-product from corn milling was employed as a growth medium at the

Sir Howard Walter Florey, co-awarded the Nobel Prize for Medicine 1945. Penicillin, which is produced by Penicillium chrysogenum, was discovered by Alexander Fleming in 1929. Howard Florey, Ernst Chain and their team purified and concentrated the antibiotic – leading to extraordinary success in the treatment of infections during World War II. In 1945 Fleming, Florey and Chain shared the prestigious Nobel Prize for Medicine for their discoveries. (Image courtesy The Nobel Foundation, www.nobelprize.org)

EARTH MEDICINE: A MINERAL PHARMACY

National Center for Agricultural Utilization Research in Peoria, Illinois. This enabled ten times the amount of penicillin to be produced. Production was originally low at 4 units/ ml, with 40 units/ml being achieved with advances in the culture medium in the United Kingdom. Even so, it was more than a year before enough could be produced for clinical trials. Subsequently a strain was found that yielded 70–80 units/ml – a significant advance that led to further studies using X-rays and UV rays in the hope of inducing mutations with a higher yield. Success resulted with the production of a strain that produced 250 units/ ml. Later advances increased the yield to 900 units/ml, then 2500 units/ml. Industrialisation ultimately led to the discovery of higher yielding strains – and the development of deep-tank fermentation processes by scientists at Pfizer. Today descendants of Penicillium chrysogenum produce 50,000 units/ml (around 30 g) for drug production. In 1952 Austrian chemists at Biochemie (now Sandoz) developed the first acid-stable form of penicillin (Penicillin V) suitable for oral administration (Ligon 2004; TomVolkFungi.net; Fiechter & Beyeler 2000).

The search for high-yielding strains of Penicillium chrysogenum evaluated samples of moulds from an enormous variety of fruits, grains and vegetables. The search went far and wide and, during the Second World War, air force personnel were even encouraged to send samples of soil from across the world to the Peoria laboratories in the United States for analysis. Mary Hunt, the researcher who struck gold, gained the nickname ‘Mouldy Mary’ for her indefatigable searches. It was a mouldy Cantaloupe (Rockmelon, Cucumis melo) that was finally found to harbour the jackpot strain.

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Howard Florey featured on the $50 Australian banknote, 1973–1995.

Soil is a much more interesting topic than most people realise. Soil-based microbes have contributed to modern medicine on a vast scale, having a profound and lasting impact on human health. The unique properties of soil as a therapeutic agent lie in the role it has played in the discovery of antibiotics.2 It has been a remarkable resource for antibioticproducing bacteria, with around 50 per cent of the antibiotics that have been discovered produced by a single bacterial order, the Actinomycetales. One genus rates particular importance – Streptomyces (Abrahams 2002).   The selection of ordinary soil as a candidate raw material for a drug production enterprise may appear unlikely. Yet this is exactly what happened in the 1940s when some innovative investigations tackled the concept of dirt possessing antibiotic activity. This led two independent researchers, botanists Paul Burckholder and Benjamin Duggar, to examine thousands of soil samples across the globe. Burckholder’s investigations at Yale University resulted in the discovery of Streptomyces venezuelae in a soil sample from Venezuela, from which chloromycetin (chloramphenicol) was isolated. This antibiotic was first used against an epidemic of typhus in Bolivia in 1947. The discovery was serendipitous, with some typhoid patients accidentally receiving injections of chloromycetin. They unexpectedly recovered – an event that was to herald the introduction of broad-spectrum antibiotics. Almost simultaneously, the hazards of inappropriate drug use were to become apparent. 2 Not all forms of earth have antibiotic properties, and it should be noted that ‘antibiotic’ is a specific term that refers to microorganisms that kill or inhibit the growth of other microorganisms.

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Stained Penicillium sample. Penicillium belongs to the famous Ascomycetes classification. There are around 300 species of these soil fungi, many of which are food spoilage moulds. A number are used as flavouring agents – for example, various Penicillium spp. are the moulds found in blue cheeses, while P. camemberti and P. roqueforti are used to make Camembert, Brie and Roquefort. There are, however, also numerous species that produce highly poisonous mycotoxins. (Image courtesy Peter Halasz)

The subsequent widespread and indiscriminate use of chloromycetin revealed the potential of the antibiotic to cause serious side-effects, notably blood disorders that included severe anaemia. Eventually the drug was replaced by penicillin, which was a safer alternative – although penicillin sensitivity was a serious side effect for some people. Even so, chloromycetin has remained of value for specific conditions, including the treatment of drug-resistant Staphylococcus bacteria. It continues to be employed in typhoid, salmonella and meningitis infections. Benjamin Duggar, a 71-year-old professor of botany, began his search for an antibiotic that would effectively treat tuberculosis, and was to discover another, quite different therapeutic agent. In the 1940s, at the University of Wisconsin, Duggar reviewed over 30,000 soil types to eventually unearth a vitally important antibiotic on his doorstep – which, strangely enough, was developed from microbes only found in a cemetery near the university (Stetter 1993). His work revealed the potential of Streptomyces aureofaciens, resulting in the subsequent development of aureomycin (chlortetracycline). Although ineffective in tuberculosis, it had a good broadspectrum activity similar to chloromycetin. Around the same time, in 1943, the

‘Penicillin cures Gonorrhoea’: educational poster from World War II. (Courtesy Kay Latimer, CDC, Public Health Image Library)

antitubercular antibiotic streptomycin was extracted from Streptomyces griseus by Selman Waksman – an actinomycete he had originally examined 28 years earlier when working on his doctorate. While useful for the treatment of tuberculosis, it was not as safe as penicillin for general use. A serious side-effect was the development of deafness due to nerve damage, therefore improvements in drug development continued to be imperative (Sneader 1989). Thereafter, in the late 1950s, a flurry of tetracycline drugs became commercially available.

Selman Waksman was a professor of biochemistry and microbiology at Rutgers University whose work led to the discovery of over twenty ‘antibiotics’, a term which he coined. In 1952 he was awarded the Nobel Prize for Physiology or Medicine in recognition of the discovery of streptomycin – ‘the first antibiotic active against tuberculosis’. Neomycin was another important antibiotic that originated from his work. (Image courtesy Library of Congress Prints and Photographs Division: New York World-Telegram and the Sun Newspaper Photograph Collection, taken by staff photographer Roger Higgins)

EARTH MEDICINE: A MINERAL PHARMACY

Their   use was to cause unforeseen problems linked to serious imbalances of the normal bowel flora. There was also the evolution of bacterial strains resistant to tetracyclines. Inevitably their deployment declined, although today they continue to have a role in treating specific infections due to organisms such as rickettsia, mycoplasma, brucella, psittacosis and various chlamydial infections, including trachoma.



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indicator for faecal contamination studies and some strains have been responsible for food poisoning. Pathogenic fungi rate equal concern, particularly Aspergillus, which can cause serious lung infections in immunosuppressed individuals, notably those suffering from AIDS. Desert/Valley fever or Desert rheumatism (coccidioidomycosis), a flu-like illness associated with extreme fatigue, has been associated with archaeological excavations. This is due to dust contamination with the spores of Coccidioides immitis, a fungus that prefers hot, dry conditions. The condition has been associated with severe pneumonia and meningitis – and fatalities have occurred. In addition, a soil mycobacterium (Mycobacterium avium subsp. paratuberculosis) can be a cause of infection in dairy herds (Abrahams 2002).

Low-temperature electron micrograph of a cluster of rod-shaped Escherichia coli bacteria (family Enterobacteriaceae), magnified 10,000 times. (Image courtesy Erice Erbe, digital colourisation by Christopher Pooley, Agricultural Research Service, US Department of Agriculture, Image Gallery)

There are numerous pathogenic organisms present in soil. While most of us would be familiar with the risk of contracting tetanus (Clostridium tetani), soil can also contain spores responsible for gas gangrene (C. perfringens) and bacteria such as Pseudomonas aeruginosa. The latter is of concern as an antibioticresistant pathogen that has become prevalent in hospitals. Faecal material in soil has the potential to contaminate water supplies with bacteria (Escherichia coli, Leptospira), protozoal parasites (Cryptosporidium, Giardia), cyanobacteria and some viruses. Some of these pathogens, for example E. coli, can remain viable for several months3 (Bisi-Johnson 2010; Abrahams 2002). Indeed, this bacterium can be used as an 3 It should be noted that not all forms of E. coli are pathogenic – and that some strains have even been included in probiotic formulations.

Cultures of various fungi and bacteria including Penicillium and Aspergillus. Over 60 species of Aspergillus have pathogenic potential – often being involved in skin lesions, ear infection and ulceration. (Image courtesy Dr David Midgley)

The numerous antibiotics that were discovered from soil origins have had a remarkable influence on the provision of commercial drugs – with an enormous range of antimicrobial agents being developed (Sneader 1989): •  Erythromycin, discovered in 1952 in the Philippines from Streptomyces erythreus, was found to have activity similar to penicillin. • Penicillium janczewskii was isolated from soil samples from sites in Dorset (UK) where Conifers would not grow. The bacterium was toxic to fungi essential for the trees’ growth. From these origins

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came griseofulvin, a drug that continues to be used for intractable fungal skin infections. • Streptomyces nodosus was found in soil samples from the Orinoco River in Venezuela. This was the origin of amphotericin, which continues to be one of the most important antibiotics available for treating systemic infections, particularly for cancer chemotherapy patients with a compromised immune system. It is very similar to nystatin, another soil-based antifungal antibiotic that, although suitable for external use, was found to be too toxic for internal use. • The rifamycins are a class of antibiotics discovered in the late 1950s from Streptomyces mediterranei. Nocardia mediterranea was later found to be a good source of rifamycin B. This was of particular interest because, although this chemical had a low level of antibacterial activity, it could oxidise to a more potent agent. These discoveries finally led to the development of a derivative with significant activity against tuberculosis. Equally impressive was the subsequent development of a range of anti-cancer drugs primarily isolated from species of Streptomyces. Unfortunately many of the drugs had serious side-effects that limited their practical value, although a couple of the most successful, such as doxorubicin (adriamycin), remain in clinical use. The following summary indicates the most influential discoveries (Oliver-Bever 1971; Sneader 1989): Actinomycin A from Actinomyces antibioticus •  (1940). Actinomyces are ubiquitous soil organisms with features common to both bacteria and fungi. This was the first antibiotic isolated from an actinomycete, although it was far too toxic for clinical use. Actinomycin C (cactinomycin, an antibiotic •  complex) was isolated from Streptomyces chrysomallus (1949). It could produce partial remissions in Hodgkin’s disease and avoid the premature rejection of organ grafts. • Actinomycin D (eventually named dactinomycin) was isolated from Streptomyces parvullus (1953) – a highly active compound that provided a chance of remission in a number of rare forms of cancer – e.g. choriocarcinoma (cancer of the placenta), and Wilms’ tumour (a rare kidney cancer), muscle

Cultivation of Nocardia and Streptomyces gram-positive bacterial colonies, showing two positive results (a clear halo around the colonies), and two negative growth patterns (an absence of this clear halo, with the deposition of a melaninlike pigment). Both genera are members of the order Actinomycetales. (Image courtesy Dr David Berd, CDC)

Slant cultures demonstrating variations in colony appearance between aerobic Actinomycetes spp. – white colonies (Actinomadura madurae), yellow colonies (Nocardia asteroides), and red colonies (Micromonospora spp.). (Image courtesy Dr David Berd, CDC)

tumours (rhabdomyosarcoma), bone cancer and Hodgkin’s disease. However there were numerous toxic side-effects that limited its use – although it continues to be incorporated into some combination anticancer treatments.

EARTH MEDICINE: A MINERAL PHARMACY

Other antibacterial and anticancer drugs of note include: • Rufocromomycin from Streptomyces rufocromogenes (1952). • Mitomycin from Streptomyces caespitosus (1956). • Bleomycins from Streptomyces verticillus (1962). •  Rubidomycin (daunomycin) from Streptomyces coerulorubidus (1962) •  Daunorubicin (daunomycin, rubidomycin or cerubidin) from Streptomyces peucetius (1962). •  Adriamycin (doxorubicin) from Streptomyces peucetius (1967) was to become one of the most successful antitumour drugs ever discovered.

  Native Streptomyces Antibiotics The presence of endophytes within plant tissue is relatively uncommon, and their detection, particularly those from the genus Streptomyces, is of significant interest as antibacterial agents.4 Investigations have discovered a couple of unique Streptomyces from Snakevine (Kennedia nigricans) and the Fern-leaved Grevillea (Grevillea pteridifolia). They have been a source of novel antibiotics – munumbicins and kakadumycins, respectively. Indeed, the Fernleaved Grevillea yielded ‘the most biologically active endophytic Streptomyces spp. on record’. In particular, kakadumycin A had a broad spectrum of antibiotic activity, especially against gram-positive bacteria, and impressive activity against the malaria parasite (Plasmodium falciparum) (Castillo 2003). Snakevine, which has been utilised by Aboriginal people as a remedy for open bleeding wounds, also had a reputation for preventing infection. Overall 39 different Actinomycetes endophytes (primarily Streptomyces species) have been isolated from different Snakevine plants sourced from the Northern Territory – and, although the majority of these did not have antibiotic properties, at least seven were of interest for further evaluation (Castillo 2006, 2005). Of these, munumbicins (actinomycin 4 The term ‘endophyte’ describes a symbiotic relationship of a microbe within a plant. This can refer to various microorganisms (including bacteria and fungi) that reside inside healthy tissue, without causing disease.

The Fern-leaved, Golden or Silky Grevillea (Grevillea pteridifolia) was first collected by Joseph Banks near the Endeavour River, Cooktown in northern Queensland. The species name is derived from Greek pteris, ‘fern-like’, referring to the foliage. The flowers are particularly nectar-rich and the tree has gained fame as an ornamental, being used to produce many of the popular Grevillea hybrids.

antibiotics) were isolated with highly active antibacterial activity, notably against multi-drug resistant Mycobacterium tuberculosis and grampositive bacteria, as well as antifungal activity against Pythium ultimum. Of particular interest was their activity against MRSA and against the malaria parasite (Plasmodium falciparum). Indeed, in comparison the conventional antimalarial chloroquine, some munumbicins showed significantly greater activity (Castillo 2006, 2002). With regard to Snakevine the authors of the research paper (Castillo 2006) concluded: ‘It seems evident that this one host plant, the snakevine, with its complex of streptomycetes, alone can act as a veritable pharmacy to

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native peoples using it as a source plant to treat open bleeding wounds. There seems to be an unlimited number of other bioactive Streptomyces spp. associated with this interesting native plant.’ Endophytic Streptomyces with antifungal properties have also been isolated from herbal medicine plants from the Malay Peninsula, notably Thottea grandiflora (Aristolochiaceae), Polyalthia spp. (Annonaceae), and Mapania sp. (Cyperaceae) (Zin 2007). The latter two genera are found in Australia, with four native Polyalthia species (P. australis, P. michaelii, P. nitidissima, P. patinata), and one species of Mapania (M. microcephala) from the northern tropics (coastal Queensland and Northern Territory) and Papua New Guinea. Doubtless there are other native species about which little is known, notably those from the rainforest and marine environments, that would also be good candidates for review.

Antibacterial Earth

The use of earth (which is classified as a geological nanomaterial) as a healing agent for skin infections is one of the ancient customs that fell into disfavour in modern medical practice. However, considering the origins of antibiotic therapy, it should be no surprise to find that research has been gradually substantiating this old practice. Specific clay minerals (notably iron-rich clay) may prove valuable in the treatment of bacterial diseases, including drug-resistant infections. Recently, African clay poultice treatments for Buruli ulcer infections due to Mycobacterium ulcerans were found to give excellent clinical results, with complete healing and minimal scarring.5 The condition is problematic to treat as it responds poorly to antibiotics in the ulcerative stage, and surgical intervention can result in significant disfigurement (de Courrsou 2002; Weir 2002). The explanation of the clay’s activity was discovered to be quite a complex affair. Two types of French Green clay (iron-rich smectite and illite) were involved in the treatment protocol, and they were eventually shown to have quite different properties. In an intricate piece of detective work, it was found that one type had a significant antibacterial effect6 – while the other had more potent healing properties. This was linked to their mineral composition. The clay type (CsAg02) possessed an extremely broad spectrum of antibacterial activity against Escherichia coli and ESBL (extended-spectrum β-lactamase E. coli), Salmonella enterica serovar. typhimurium, Pseudomonas aeruginosa, Mycobacterium smegmatis, M. marinum7, Staphylococcus aureus (as well as PRSA, penicillin-resistant, and MRSA, methicillin-resistant, S. aureus). However, while the second clay type had a similar 5 WHO figures estimate around 5,000 cases occur each year. However, this is likely to be an underestimate of the incidence of the condition which, in Africa (primarily Benin, Ghana, Côte d’Ivoire), is more prevalent in children 5–15 years old (Walsh 2011)

Snakevine, Kennedia nigricans (syn. Caulinia nigricans; Fabaceae). This is an attractive legume of Australia’s southern coast that ranges from New South Wales to the Northern Territory and Western Australia, as well as being found in Tasmania. (Image courtesy SatuSuro, Wikimedia Commons).

6 Because clay minerals are not produced by microorganisms they are not considered to be antibiotic in nature. They are classified as antibacterial – which means they can have bacteriostatic (inhibitory effect on microbial growth) or bactericidal activity (bacteria-killing activity). Antibacterial agents differ in their range of activity and, depending on the target bacteria involved, they have variable bacteriostatic or bactericidal effects. Broadspectrum agents are effective against a range of different bacteria (Williams & Haydel 2010). 7 M. marinum (which is related to M. ulcerans) can cause nodular and ulcerated skin lesions. It is often associated with exposure to contaminated water from aquariums, swimming pools and some marine environments – and includes marine animal stings or bites. The infection has the potential to be particularly problematic because it can invade into deeper muscle and bone tissue (Walsh 2011; Haydel 2008).

EARTH MEDICINE: A MINERAL PHARMACY

structure and chemistry (CsAr02)8 it was inactive (or even promoted bacterial growth) – showing that the antimicrobial activity was quite specific and influenced by the clay’s mineral composition. The conundrum was that the CsAr02 clay was found to actually promote experimental bacteria growth, particularly that of Escherichia coli (Williams & Haydel 2010; Haydel 2008). The causative bacterium of the Buruli ulcer, Mycobacterium ulcerans, has a complicated modus operandi. It utilises a necrotising (tissue-destructive) immune-suppressant mycolactone toxin that compromises the patient’s immune reaction. It was postulated that the smectite component of the CsAr02 clay could initially bind to the toxin, facilitating its removal when the poultices were first changed. This clay however, was only used for a short time at the beginning of the treatment, before switching to the CsAg02 antibacterial clay. This would have effectively sterilised the wound. A normal immune response could then proceed. It was possible that the clay allowed the normal bacteria to re-establish and thereby initiated a natural immune response. Afterwards healing could proceed naturally, with the associated skin granulation facilitating wound repair. Interestingly, the clay did not physically penetrate the bacterial cell. Thus it appears that the water in contact with the clay, and subsequent cation exchange, resulted in the creation of a chemical environment that stopped the pathogenic bacteria thriving9 (Williams & Haydel 2010; Williams 2008).

8 Both clays were primarily composed of iron-rich smectite and illite clay minerals. However, CsAg02 was enriched with magnesium and potassium, while CsAr02 was calcium-enriched. 9 Clay sourced from the Cascade Mountains, Oregon, USA, has shown similar activity.

    A Matter of Transmission

The Australian Daintree or Bairnsdale ulcer, which is the same as the African Buruli ulcer, is a necrotising (‘flesh-eating’) form of mycobacterial infection with a characteristic ulcerative presentation. The condition appears to be increasing in incidence. Over 44 years (1964–2008), 94 cases were recorded across

Daintree River and mangrove lowlands.

the country, and were usually treated surgically – in some cases, the disease progression resulted in repeated surgery and skin grafting (Steffen 2009). Although reports during 2008–10 were low (and, possibly, the condition was underreported) with 18 cases, in 2011 a massive outbreak recorded 64 cases in Queensland (WHO Collaborating Centre for Mycobacterium ulcerans, Western Pacific Region, Victoria, Australia). The condition appears to be associated with an insect bite or minor trauma that does not heal, slowly progressing into an unsightly ulceration that is unresponsive to antibiotic treatment. Many Daintree locals believe that March flies are responsible for spreading the infection, although mosquitoes appear to be equally good candidates. A study of 14,889 mosquitoes captured during an outbreak of the disease at Port Lonsdale (south of Melbourne) showed that five different species could carry Mycobacterium ulcerans – possibly acquiring it through environmental exposure or acting as a vector reservoir (Lavender 2011; Wallace 2010; Johnson 2007). Certainly, there appears to be a correlation with areas associated with outbreaks of other mosquito-transmitted disorders such as Ross River fever and Barmah Forest virus (Johnson & Lavender 2009). To date, the issue of transmission remains unresolved. Different vectors may be involved in other environments. In Cameroon, the saliva of biting water bugs (7,407 samples) demonstrated the presence of Mycobacterium ulcerans – and it

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possum (Pseudocheirus peregrinus) and Common Brushtail possum (Trichosurus vulpecula) in areas where outbreaks of M. ulcerans infection have occurred – although the bacterium could not be cultured from these samples. Overall levels of infection or faecal contamination were 38 per cent and 24 per cent, respectively. In comparison, faecal contamination in possums from nearby uninfected sites was extremely low (less than 1%) (Fyfe 2010; van Zyl 2010). Certainly, it suggests that this bacterium has more problematic potential than initially appreciated – for wildlife, domesticated animals, and humans.

Blood-engorged mosquito. (Courtesy Gathany, CDC PHIL Library)

James

has been suggested that environment changes due to human activity could be facilitating transmission of the disease (Williamson 2012; Marion 2010). Moreover, there may well be a level of animal interaction resulting in an environmental reservoir for the disease. In Australia, Mycobacterium ulcerans infections have been recorded in horses, cats, dogs, native possums and koalas in areas where the infection is endemic (O’Brien 2011; Fyfe 2010; van Zyl 2010; Elsner 2008). In Victoria, high levels of mycobacterial (M. ulcerans) DNA has been detected in faeces from the Common Ringtail

Common Brushtail possum. (Courtesy Arthur Chapman, flickr)

Investigations of the iron-rich clay established that the mineral components buffered the pH of the solution and supported oxidation processes. Eventually conditions develop that result in increased iron solubility, creating an iron-saturated solution. Ultimately the iron was able to enter the bacterial cell and kill it (Williams 2011). Iron oxide (magnetite) has shown bactericidal activity against Staphylococcus aureus. It was also able to increase the growth of human bone cells, although the tissue-growth properties of clay remain unexplained (Williams 2011; Tran 2010). This is not the only method by which clays can exhibit antibacterial properties. There are a number of other soluble clay components are toxic to bacteria: •  Allophane and imogolite-based clays have a chemical sorption process that deploys a number of bactericidal elements: copper, zinc, silver and cobalt (Williams 2011). Jordanian red earth from the Mediterranean •  is a traditional treatment for skin infections and diaper rash. Soil samples, obtained from uncontaminated sites (i.e. away from industrial activity or urban settlements) demonstrated good

Iron oxide. (Courtesy Ben Mills, Public Domain, Wikimedia Commons)

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antibacterial potential against Micrococcus luteus and Staphylococcus aureus. In this instance, the activity appears to be dependent upon a number of component antibiotic-producing bacteria – Actinomycetes, and strains of Bacillus and Lysobacter. The actinomycetes synthesised specific antibiotics (Actinomycins C and C2) upon pathogenic bacteria exposure (Falkinham 2009).

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Zeolites have rather extraordinary adsorptive10 and absorptive capacities and a high cation exchange capacity, with a useful affinity for oxidised silver ions. Silver-enhanced zeolite can thereby acquire broad-spectrum antibacterial properties against gram-negative and gram-positive bacteria, including Pseudomonas aeruginosa, Streptococcus aureus, S. mutans and S. sanguinis. This form of zeolite has particularly useful dental applications. Zinc oxide has also been utilised in dental composites for treating tooth caries and as a sealant. Vermiculite is another clay mineral that acquires antibacterial properties when loaded with copper ions – which has potential as an antifungal agent (Williams & Haydel 2010).

Sinkholes at Mineral Beach, Dead Sea, West Bank. Dead Sea ‘black mineral mud’ has shown antimicrobial (bacterial inhibitory and bactericidal) potential against Escherichia coli, Staphylococcus aureus, Propionibacterium acnes and Candida albicans. This hypersaline clay has been widely used for cosmetic purposes (Ma’or 2006). (Image courtesy Doron, Feldman)

Antibacterial Metals Metallic oxides (silver, copper, zinc, magnesium, calcium) have shown various levels of bacterial inhibitory and bactericidal properties. Silver-loaded clays have, however, gained centre stage as far as recent research is concerned. Silver-ion based preparations have been utilised as antibacterial agents for treating burn wound infections, osteomyelitis, urinary tract infections, and infections due to venous catheters (Williams & Haydel 2010).

Native copper, naturally-occurring copper that is devoid of impurities. (Courtesy Jonathan Zander)

Copper has a broad spectrum of antimicrobial activity – and an extremely long history of use. Malachite, a highly attractive green-coloured mineral composed of copper carbonate, is of particular interest as a cosmetic ingredient.11 Powdered 10 To adsorb something, or the process of adsorption, refers to a process that involves the attraction, binding and accumulation of particles on a solid surface in a condensed layer. Absorption differs in that a substance diffuses/penetrates into a liquid or solid. In the latter process a transition zone is formed adjacent to this substrate, and this new layer can have a different chemical composition (Williams & Haydel 2010).

Silver. (Courtesy Teravolt.org, Wikimedia Commons)

11 The mineral malachite should not be confused with the synthetic ‘Malachite green’ (triphenylmethane dye) – an antimicrobial dye that has been used for over 50 years in mycobacterial culture studies to inhibit the growth of contaminants. It is a useful indicator that changes colour in response to Mycobacterium tuberculosis growth and has therefore been used in the diagnosis of tuberculosis and in drug efficacy studies (Farnia 2008). ‘Malachite green’ is commonly used in the fish farming industry as an antifungal, antiparasitic and antibacterial agent. It has also shown effective anti-Candida activity (Dhamgaye 2012).

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aeruginosa. Malachite was also utilised as a wound dressing – Egyptian records mention its use for a burn that had become infected (‘foul’) and a breast wound (Nunn 1996).

Ancient copper ingot from Crete, showing animal skin pattern. Copper is a rather remarkable mineral that was used medicinally by the Ancient Egyptian, Greek and Roman cultures. It was the Romans who named the metal cyprium (now cuprum), ‘metal of Cyprus’, as it was mined on this island. The Greeks, who had copper mines on Crete, sprinkled copper oxide and copper sulphate powders on wounds to prevent infection. A decoction of red copper oxide and honey was similarly utilised. The use of copper as a storage vessel (e.g. for water) was also noted to prevent contamination (Dollwet & Sorenson 1985). (Image courtesy Chris 73, Wikimedia Commons CC-bySA 3.0 Unported)

The ancient Edwin Smith Papyrus, which is the world’s oldest surgical document (1600 BC), mentions the use of copper alloy filings from swords being dropped into chest wounds to sterilise them. The Ebers Papyrus (see picture page 193) notes the use of copper compounds for treating headaches, burn wounds, itching and neck ‘growths’ (which would have included boils). (Image from the Rare Book Room, New York Academy of Medicine, courtesy Jeff Dahl, Public Domain, Wikimedia Commons)

malachite has antibacterial properties that support its extensive use in Ancient Egypt. Experimentally malachite or its main component (cupric carbonate or hydroxide) has an inhibitory effect on diverse bacteria, including Staphylococcus aureus and Pseudomonas

Copper was discovered at Cobar, western New South Wales, in 1870 – with the Great Cobar Copper Mining Company Ltd being established in 1878. The open cut mine (pictured) has also been a source of zinc, lead, silver and gold. (Image courtesy Axel Strauss, Wikimedia Commons, CC-by-SA 3.0 Unported)

In the 1800s, during cholera epidemics in Paris (1832, 1849, 1852), copper workers were observed to have immunity to the disease, which suggested some sort of antibacterial effect. A few decades later, during the 1880s, copper arsenate was deployed in treatments for acute and chronic diarrhoea, dysentery and cholera. The pharmaceutical company Bayer developed an organic copper complex for tuberculosis – a remedy that was utilised until the discovery of antibiotics in the 1940s. Diverse copper preparations have also been effective for treating chronic adenitis (lymph gland inflammation), eczema, impetigo, scrofula, lupus, syphilis, anaemia, chorea and facial neuralgia (Dollwet & Sorensen 1985). A particularly interesting record from Suffolk was published in The Daily Express of 1943: ‘Mrs. Eva Wood[’s] … great-grandmother used to collect all the new copper pennies she could, old copper kettles, smear them with lard and leave them in a damp place. When the mould had formed she would scrape it off into little boxes and everyone for miles around came to her for the remedy for what ailed them’ (Wainwright 1989b). An intriguing strategy that may well have introduced a copper component into the antibacterial mould growth. Copper also has anti-inflammatory properties. In

EARTH MEDICINE: A MINERAL PHARMACY

Malachite has been sourced primarily from Russia (Ural Mountains), France, Africa (Zaire, Namibia), America (Arizona), Morocco, Brazil and Mexico. Australia also has a number of famous sites: Burra Burra (South Australia); Rum Jungle (Batchelor, Northern Territory); and the Sir Dominick Mine in the Flinders Ranges (South Australia). (Upper image courtesy Heather Rabbich, Cairns; image of Rum Jungle malachite below courtesy Rob Lavinsky at irocks.com)

1885 the French physician Luton reported the use of copper for treating arthritis, employing an ointment made from hog’s lard and 30 per cent neutral copper acetate. Later, in the 1940s, Finnish copper miners were noticed to be immune to the ravages of arthritis – an observation that led to a series of successful clinical trials utilising a mixture of copper chloride and sodium salicylate for treating rheumatic fever, rheumatoid arthritis, sciatica, neck and back disorders (Dollwet & Sorensen 1985). Recently, investigations of the use of copper-based preparations as a transdermal anti-inflammatory remedy have also shown good results (Hostynek 2009). Studies have established that copper not only has inhibitory effects on bacteria and fungi – the mineral also possesses antiviral properties and can inactivate polio and influenza viruses. Indeed, the antimicrobial effects of copper are of sufficient potency to attract serious interest in manufacturing antibacterial surfaces that can reduce microbial transmission – particularly for use in health care institutions, notably hospitals.

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In comparison, microbes were found to persist on stainless steel at a much higher rate, thereby increasing the risk of contamination. Operating theatres could certainly be made much safer if infection risks were significantly reduced by microbe-resistant surfaces and air-conditioning systems (Weaver 2010; Michels 2009, 2003; Noyce 2007; Barker 2004; Noyce & Keevil 2004; Keevil 2000; Chang & Tien 1969; Avakya & Rabotnova 1966; Colobert 1962). To gain some idea of the potency of copper, a study of the incubation of the influenza A virus is relevant. After 24 hours on stainless steel 500,000 influenza A virus particles remained infectious – while after only 6 hours on copper, merely 500 particles were active (Noyce 2007). The results regarding other highly problematic hospital pathogens such as MRSA (methicillin-resistant Staphylococcus aureus)12 and Clostridium difficile were similar. Copper surfaces completely inhibited the viability of the bacteria, while stainless steel had no effect. The implications are of great significance (Weaver 2008).

Magnified image (440x) of rolled and annealed brass. Copper is not a highly durable metal, thus copper alloys make a better choice of material for most purposes because they are more resistant to corrosion. Copper can be used to make tin (with bronze, although aluminium and silicon may be present), copper-nickel (with nickel), nickel silver (with nickel and zinc), leaded copper (with lead) – as well as being combined with precious metals such as silver and gold. Brass is a copperzinc alloy that was used to make many of the fittings in old houses, such as doorknobs. Interestingly, they would appear to have exerted an intrinsic antibacterial effect due to the copper component of the metal – a truly extraordinary revelation (Wilks 2005). (Image courtesy Strangerhahaha, Wikimedia Commons, Public Domain) 12 The development of drug-resistant bacteria occurred early in the history of antibiotic use. Reports initially surfaced in 1942, and a mere decade later a significant number of Staphylococcus infections fell into this category. The drug methicillin was discovered in 1960, although its use also became compromised by the subsequent development of MRSA – the infection that plagues hospitals and those with poor immunity. Thereafter, bacteria resistant to multiple antibacterial drugs became increasingly problematic. Vancomycin remained in use for some time until, again, resistant strains developed (Sternbach & Varon 1992).

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    Minerals as Paint and Paste

Queen Nefertiti (ca. 1370 BC – ca. 1330 BC), bust in the Neues Museum, Berlin, illustrating the eye makeup traditions of Ancient Egypt. (Image courtesy Arkadiy Etumyan CC-by-SA 3.0 Unported)

The potential of minerals as antibacterial agents has inspired their use since ancient times. Indeed, the use of ochre to cover skin blemishes was practised in Ancient Egypt. It was among the tomb treasures of this land that the first evidence of cosmetics was discovered. The Ancient Greeks and Romans were equally fond of personal decoration – although, at times, a substantial amount of experimentation with toxic metals occurred. Perhaps one of the most noticeable uses of cosmetics in Egyptian traditions was that associated with the art of eye decoration, notably mascara. Eye disorders in this region were rife – conditions such as conjunctivitis, trachoma (due to Chlamydia trachomatis), corneal ulcers, cataracts and diverse other inflammatory eye disorders were prevalent. The black kohl (ground lead sulphide) and green eyeliner (powdered malachite) were not only utilised for decorative purposes – they

had significant antibacterial potential. Eye disorders were treated with numerous recipes, many of which included these two minerals with additives such as natron13 and fermented honey. Two types of earth were also used in many prescriptions (a common ochre and red ochre) – as were common herbs, including acacia, carob, celery and hemp (Nunn 1996; Manniche 1989). Kohl cosmetic tube inscribed with the cartouches of Amenhotep III and Queen Tiye. Unsurprisingly, concerns with regard to lead poisoning have surrounded the use of traditional kohl-based makeup and eyeliners. (Image courtesy Keith Schengili-Roberts, Creative Commons CC-by-SA-2.5)

Mascara (kil) and container (kiledan). (Courtesy Ako Mahmoodi, Kurdistan)

13 Natron was readily available in dry lake beds around Ancient Egypt. It is primarily a mixture of sodium carbonate (a form of soda ash), sodium bicarbonate (baking soda), with small amounts of sodium chloride (halite, salt) and sodium sulphate. Like normal salt, natron was utilised as a drying, preservative salt for foods such as fish and meat (Nunn 1996). Natron was widely employed as a household cleaning agent – and was integral to the embalming process. Interestingly, it was used for making a smokeless fuel with castor oil, a good light resource that allowed tomb painting works to proceed without unsightly smoke stains developing. It was also an essential component of the ‘Egyptian blue’ dye.

EARTH MEDICINE: A MINERAL PHARMACY

Traditionally, mascara or kohl was prepared from a dark grey form of lead ore (galena). Lead chlorides (laurionite and phosgenite), which were not naturally found in Ancient Egypt, were deliberately synthesised for use as fine powders for makeup and eye lotions. They were prepared from lead oxide powders (litharge) combined with rock salt (and possibly natron) in warm water. The Romans (1st century AD) were equally familiar with these compounds, their expertise originating from Egyptian traditions. Dioscorides provided a detailed description of the manufacture of these lead chlorides, which was a fairly delicate chemical process. He also mentioned their medicinal qualities: ‘[they] appear to be good medicine to be put in eyes, and for foul scars, and for faces wrinkled and full of spots’ (Tapsoba 2010). A recent investigation tends to suggest that these cosmetics had a valid therapeutic basis: ‘the eyes of Egyptians bearing the black makeup were presumably prone to immediately resist a sudden bacterial contamination with extreme efficiency through the spontaneous action of their own immune cells’. The study suggests that a stimulation of the innate activity of nitric oxide supported the immune system in resisting infection (Tapsoba 2010). The Egyptians utilised many forms and colours of makeup – and, as malachite demonstrates, some were highly effective antibacterials. However, there was a serious risk of lead poisoning which, doubtless, had an effect on those applying elaborate makeup over long periods of time. Indeed, even in the 1990s it was discovered that lead levels in some commercial eye makeup from Egypt and India could be over 90 per cent – although, fortunately, not all preparations were lead-based (Hardy 2004, 2002, 1998). Mascara today is usually an amorphous charcoal or carbon-based product. The use of lead in cosmetics is, in general, banned – although this does not preclude its use as an illegal adulterant (see also ‘Lead Poisoning’, page 231).

Lead ore (galena) with calcite crystals from Elmwood mine, Central Tennessee. (Courtesy Rob Lavinsky at irocks.com)

Hieroglyph for antimony. Antimony is a highly toxic lustrous silvery-grey metal. In ancient times it was widely used as an ingredient in kohl cosmetic preparations. (Image courtesy Wikipedia)

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Laurionite (above) and phosgenite (below). The phosgenite sample is on display at the Vale Inco Limited Gallery of Minerals, Royal Ontario Museum. (Upper image courtesy Rob Lavinsky at irocks.com; lower image CaptMondo CC-by-SA 3.0 Unported)

Stibnite (antimonite), which is the mineral source of antimony, has been mined in Australia since the 1800s. Indeed, a quote from the Proceedings, Royal Society of Queensland (Lindon 1887) commented: ‘The association of gold and stibnite is not common, but it occurs in New South Wales, Victoria, Brazil, Transylvania, and in the Kingdom of Siam’. (Image courtesy Rob Lavinsky, irocks.com)

Pharmacy preparation of Antimony, which was well known for its poisonous properties. (Image from Herberton Historical Village, Atherton Tablelands, north Queensland).

EARTH MEDICINE: A MINERAL PHARMACY

Earth as a Poison Antidote

Clay deposit from Estonia, estimated to be around 400,000 years old. (Courtesy Siim Stepp, sandatlas.org)

The subject of the medicinal value of earth lends itself to an examination of the ancient use of special clays as detoxicant and remedial agents. Indeed, Terra Sigillata (‘sealed earth’) has long been utilised as a woundhealing agent, poison antidote, gastrointestinal and febrifugal remedy. The Pharmacopeia Londinensis or, the New London Dispensatory, Translated into English by William Salmon (1678) describes the physical properties of Terra Sigillata and its medicinal reputation: Sealed Earth: There are several sorts of Sealed Earth … viz. that from Constantinople, which is an ash colour, and indeed the best of all Earths which are known to us: though that of Lemnos [Cyprus] which is red, is often used for the true. The best Earth is known 1. By the sticking to the tongue. 2. If cast into water it rises up in bubbles. Terra Sigillata is drying, binding, sudorific… and resisting Plague, Poyson, Putrefaction, and all kinds of Malignity and Venom. It is chiefly used against the Plague, malignant Fevers, Diarrhoea, Dysenteria and biting of venomous Beasts etc …

In 1579 a German translation of a Latin work on the subject by Bertholdus (1583) was made by Johann Wittich. The text provides a discussion on the detoxicant properties of Terra Sigillata at some length (cited in Dannenfeldt 1984): For poisons eaten, drunk, or obtained in any way, a full drachm of this earth (more or less, depending on the type of poison and the age and condition of the patient) should be taken in any appropriate distilled water. If the poison was newly received, vomiting would occur. If the

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earth is taken some time after being poisoned, the patient should lie in bed, well covered, and sweat out the poison. If distilled waters, like those of blessed thistle, devil’s bit, swallowwort, butterbur, angelica, or pimpernell are not available, the earth could be taken in white wine.   The new sealed earth can be taken in like manner against the plague, especially by those already infected. For preservation from a plague threat, one takes half a drachm in the morning in wine, vinegar of marigolds, or in any other convenient distilled water. Berthold reported that in pestilential times he had successfully given immediately one drachm of Silesian earth in wine, or distilled water, vinegar, or both to persons who had experienced the first manifestations of the plague, like pains in the heart and head, or any ‘anguish, grudging, lothsomeness, guiddiness’, or other signs. The patient is sent to bed, well covered, to sweat out the poison. In a few hours, the poison is driven out without any external boil or swelling.   If the remedy is delayed and the plague infects most of the blood, a sore or carbuncle appears. In such cases, the vein nearest the plague sore must be opened. When the evil humours have thus been qualified, the heart will drive the poison to the sore, which, when ripe, should be lanced by an expert surgeon. Care must be taken that a little of the earth, steeped in vinegar and cinnamon, is put in a plaster and laid on the heart. The plaster, it will be observed, draws out a great quantity of poison. One must also remember that after the medicinal earth has been administered, the patient must place a piece of toast wet with good vinegar to his nose to prevent regurgitation of the earth. If swallowed earth is vomited, the patient should be administered earth until it is retained …   For headaches caused by great heat, heavy labour, or wind, sleeplessness caused by worry or a troubled mind, the spirit is restored if in the morning one takes a drachm of the earth with good brandy, or with water of betony, rosemary, marjoram, pennyroyal, or such like. For pains and trembling of the heart, the earth assuages the trouble if a drachm of it is taken with waters of balm, celandine, motherwort, bugloss, borage, or gilliflower, or drunk in good white wine. Also, for inflamed and running eyes, or bleariness, temper this earth with rosewater or water of plantain, eyebright, valerian, fennel, or similar distilled water, dip into this a black hen-feather, and let a drop fall into the eyes. Or dip a linen cloth in the water and lay it on the eyes. For wounds in the eye, see a doctor and then put sealed earth and eggwhite or a suitable water on a cloth and lay it on the eyes. For wounds of the head or testicles, a linen cloth dipped in rosewater treated with this earth should be laid on the wound to prevent any inflammation or other dangerous condition.

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Medicinal clay or loess (‘healing earth’ or Luvos Heilerde), which mainly consists of montmorillonite, from the German manufacturer Luvos. The clay is recommended to ease gastrointestinal distress such as diarrhoea and acidic stomach conditions (heartburn) and as a nutrient supplement, notably for calcium (Limpitlaw 2010). (Image courtesy Martin C Doege, Wikimedia Commons)

Despite such praise, the value of Terra Sigillata (notably that sourced from the Striga goldmine in Germany) as a poison antidote was a matter of contention. To substantiate the value of the remedy, experiments were undertaken. Wilhelm, Landgrave of Hesse in 1580, ordered his physicians to provide good evidence of efficacy. They tested a mercury toxin and three highly toxic plant products on a group of unfortunate dogs: • Mercury toxin: A red dog with a white ring about its neck was given mercury sublimate (mercury chloride) as well as the clay remedy. He lived, albeit suffering great bouts of vomiting. A yellow cur with a white breast was given the mercury only. He later died, suffering great distress. • Aconite: A little black hound with a white tail was the third subject which was given ‘by negligence’ aconite and the clay. He lived. The fourth subject was a brindled shaggy-haired dog with a white tail which was given only aconite. He suffered terribly but was later given the clay remedy – and recovered. • Oleander (Nerium): A fifth experiment with a black cur with a white neck involved the use of Oleander (a cardiotoxin) and clay. He also suffered badly but recovered. The brown cur with a white neck that received only Oleander, did not. • Dogbane (Apocynum) leaves and roots were given to a dog which died rather quickly.

Aconite (also known as Wolfsbane or Monkshood, Aconitum napellus) is one of a number of toxic herbs prized as ornamentals – in this case for its wonderful blue flowers. Joseph Maiden mentioned, ‘There is a large demand for the dried root for the preparation of aconite liniment and tincture. The root is very poisonous, and intending growers must be warned not to mistake it for horse-radish’ (Maiden 1892). Aconite root contains cardiotoxins and neurotoxins. Poisoning is characterised by gastrointestinal symptoms (nausea, vomiting, abdominal pain), cardiac distress (arrhythmia, chest pain, hypotension), and neurological impairment (muscle weakness, numbness, paraesthesia). The heart dysfunction may not respond to treatment, resulting in fatalities. However, the root has long been utilised in traditional medicine in Asia, India and China – although this relies on soaking and boiling processes that hydrolyse and detoxify the aconite alkaloids, the level of which is reduced by around 90 per cent (Chan 2009). (Uppper image courtesy Farmer Dodds, flickr)

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In 1581 another test involving mercury sublimate was ordered by Wolfgang, Earl Hohenlohe and Lord of Langenburg. A condemned robber named Wendel Thumblardt offered to take ‘the most deadly poison devised and this new earth’. He was given mercury sublimate in a conserve of roses, with Terra Sigillata mixed with old wine administered immediately afterward. Andrew Berthold recorded: ‘In the judgement of the court physician and the apothecary, the subject was extremely tormented. However, in the end, the medicine prevailed and overcame the poison. The man recovered and was released to his parents’ (quoted in Dannenfeldt 1984).   Around the same time Cristantus of Croenburg initiated another study that involved two dogs who were given mercury sublimate, mixed with lard. Only the one that received the medicinal earth survived. The evidence was therefore quite unequivocal with regard to the use of Terra Sigillata as a protective agent against a number of serious, usually fatal, forms of poisoning. Interestingly enough, more recent studies of the use of charcoal and fuller’s earth have shown that both were effective adsorbents (binders) of mercury – with charcoal being effective at a lower dose (Oubagaranadin 2007)

Mercury ore (above), liquid mercury (above right) and cinnabarite (right) (or cinnabar) (HgS), a mercury-based ore. Cinnabar (mercuric sulphide) is the most common source of the mineral mercury. The pigment vermilion (an orange-scarlet colour) is cinnabar-derived – and quite toxic. Due to its low melting point, purified mercury can become liquid at room temperature. Oxidising acids such as concentrated sulphuric

and nitric acids, as well as aqua regia (a highly corrosive acid mixture of nitric and hydrochloric acids that can dissolve metals) have been used to prepare sulphate, nitrate and chloride salts (respectively). The mercuric chloride toxin used in the experiments on dogs mentioned by Wittich (Dannenfeldt 1984) was a white, highly toxic, soluble powdered form of mercury. The poisonous consequences of mining cinnabar were a familiar hazard that was recorded in Roman times – a task assigned to felons and slaves due to the poor life expectancy. (Image on left courtesy Rob Lavinsky, irocks.com; top, courtesy Bionerd, Wikimedia Commons, CC-by-SA 3.0 Unported; above, specimen in Staatliches Museum für Naturkunde Karlsruhe, Germany, courtesy H Zell, Wikipedia).

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Mercury for pharmacy use. Mercury was formerly prepared in many forms (oil, ointments and various combination products). Mercuric chloride, mercuric iodide and mercuric nitrate were among those utilised as an antiseptic, germicide and anti-syphilitic remedy. Despite the inherent risk of toxicity, these preparations were effective antimicrobials. Mercuric chloride had a particularly extensive reputation as a cathartic, healing agent (alterative), diuretic and antiseptic. It was recommended for all manner of diseases: gastrointestinal distress (nausea, vomiting, flatulence, constipation, dysentery), liver problems (hepatic congestion), as a purge in infectious diseases, and even as a diuretic in dropsy (fluid retention) due to heart problems (Merck Index 1940). (Image from Herberton Historical Village, Atherton Tablelands, north Queensland)

Clay for Enterotoxins   Medicinal Charcoal

Charcoal and Activated Charcoal, from the British Pharmaceutical Codex, 1934. thighs. To heal the wounds, they used charcoal powder, and sometimes just wood ashes pounded down. The aborigines never laid up with their wounds, though one wonders at it. Father has seen in a fight the skin of the head cut right through to the skill with a waddy. These deep cuts on the head were treated in the same way as those on the body – just charcoal put in them, and the wound seemed to recover in a few weeks’ time. It would without doubt kill a white man to be treated in the same way.

Campfire charcoal.

Aboriginal people in Australia have long utilised charcoal as a healing agent. Tom Petrie’s Reminiscences of Early Queensland commented: They fought very fiercely, these men; some of the gashes were terrible. Father has seen dozens on their backs, and sometimes extra deep ones on their

Charcoal is reported to have a similar adsorptive effect to clay. Indeed, the detoxicant effect of charcoal has been familiar to medicine since ancient times – and activated charcoal continues to be utilised in modern medical practice. Some recent studies have even suggested that charcoal is more effective than kaolin at adsorbing (binding) endotoxins (Dominy 2004).

EARTH MEDICINE: A MINERAL PHARMACY

The ability of clay to act as a detoxicant in the gastrointestinal tract has shown interesting protective effects in a number of disease conditions. Recommendations for clay as an antidiarrhoeal agent has been one of the tenets associated with its use since ancient times. Wittich (1579) mentioned that: ‘The German sealed earth has the power to cure catarrh. One drinks in the evening and morning, or frequently, some of the earth in white wine or other liquid to perspire immediately and find relief. For ruptures, dysentery, or diarrhoea, in the morning and evening take a drachm of this earth with water of tormentil, of oak leaves, or of acacia flowers’ (quoted in Dannenfeldt 1984). The latter are three wellrespected astringent herbal remedies. The process involved appears to be multifaceted. The adsorptive activity of the clay not only acts to bind minerals and toxic compounds, but the clay itself has a direct protective effect on the gastric mucosa. It acts to increase mucus secretion, prevent mucus breakdown, and buffers gastrointestinal pH levels.14 By staying linked to the mucous layer the clay also acts as a physical barrier (Rowland 2002). This modifies the chance of gastrointestinal disturbance, helping to reduce symptoms such as nausea, vomiting and diarrhoea. Certainly, these effects would help to explain its use by pregnant women as an antacid, ‘stomach-settling’ remedy. Furthermore, the direct antidiarrhoeal effect of clay is supported by an antibacterial action involving the adsorption of the bacteria and their toxins, including intestinal enterotoxins. Indeed, there are a number of pharmaceutical products such as Kaopectate (which has kaolin as its main ingredient) that continue to use clay as an antidiarrhoeal ingredient. Metahalloysite, a kaolin derivative, has a similar reputation (Krishnamani & Mahaney 2000; Mahaney 2000; Johns & Duquette 1991a). 14 Additionally, processing by grinding the clay removes coarse particles and can increase its pH, thereby assisting in the digestion process. However, there is the drawback that toxic elements may be concurrently made more bioavailable for absorption by the body (Ekosse 2010).

  Kaolin and Smectite The absorbent (water-absorbing) properties of mineral clays make them useful antidiarrhoeal agents because they eliminate excess water as well as gases. They have a direct protective effect

A kaolinite mineral mine in Bulgaria. Kaolinite (kaolin) is one of the most common minerals and is mined in numerous countries, notably Australia, Brazil, Bulgaria, the Czech Republic, France, the United Kingdom, Iran, Germany, India, Korea, the People’s Republic of China, and the United States. (Image courtesy Nikola Gruev, Wikimedia Commons, CC-by-SA 3.0 Unported)

on the bowel and can bind bacteria or viruses, thereby facilitating their elimination. Kaolinbased clay preparations (e.g. Kaopectate) can slow down intestinal transit times, providing the body with more time to absorb water and minerals, thereby solidifying the stools and preventing dehydration. Palygorskite (attapulgite) has a similar effect (see also Table 5.1) (Ekossi 2010; Carretero 2002; Maxwell 2000). Smectitic clays, which are richer in magnesium carbonate (MgCO3) than kaolin, have a natural detoxicant effect on the gastrointestinal tract as they can adsorb toxins (heavy metals, free radicals, pesticides). These clay types are useful for treating constipation, allergies, diarrhoea, indigestion and intestinal ulcers (Ekossi 2010). Recent studies found that dioctahedral smectite15 was clinically useful for diarrhoeal forms of irritable bowel syndrome (Chang 2007). However, smectites do not have a gastrointestinal protectant effect as they cannot survive the acid conditions of the stomach (pH 2) or even the far less acidic environment of the bowel (pH 6). Nonetheless, calcium smectite has occasionally been utilised as a laxative due to the astringent action of the calcium component. Sodium smectite may also act as a laxative by osmosis – the sodium acting to draw more water into the bowel, which in turn 15 Smecta (active component diosmectite) is a commercial product based on smectite clay that has has been utilised as an antidiarrhoeal for both humans and primates (monkeys).

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increases the volume of the faecal matter and stimulates the propulsive activity of the smooth muscle of the intestine (Carretero 2002).

Kaolin (kaolinite or attapulgite), pictured above, is an antidiarrhoeal and detoxicant remedy that is no longer used in antidiarrhoeal formulations in the United States. In 2002 Kaopectate (a kaolin and pectate formula) was reformulated with bismuth subsalicylate replacing the clay component due to concerns about high lead levels. However, the risk was not fully ascertained. Importantly, the amount of lead present in different clay samples, and its bioavailability, can vary significantly: ‘It appears that whatever lead was measured within a clay sample or within a medication like Kaopectate was assumed to be the amount of lead a person would be exposed to, which does not say anything about the true bioavailability of Pb [lead]’ (Limpitlaw 2010; see also ‘A Matter of Bioavailability’, page 272). The source of the clay would significantly influence the potential lead contamination level. The drawback of the new formulation is that bismuth subsalicylate is not recommended for children or animals. It can cause severe constipation in children, and cats cannot metabolise salicylates (Limpitlaw 2010). (Image USGS, Public Domain)

For many centuries clay was a regularly utilised as an antidiarrhoeal remedy for the armed forces. The unsanitary conditions of war and of soldiers’ camps have habitually been associated with serious outbreaks of diarrhoea. During Roman times the physician Galen carried clay ‘tablets’ with him when on campaign. Clay rations probably saved many troops from the ravages of conditions such as cholera, typhoid and the like. Indeed, during the Balkan war of 1910 the use of clay to mitigate cholera infections was reported to reduce the mortality figures from 60 per cent to a mere 3 per cent. Russian troops were given a 200 g glass vial of clay to keep in their packs as an emergency remedy during World War I. The rations of Russian and French soldiers during World War II also utilised mineral clay – with one enterprising French medical officer adding clay to custard as a preventative for the ‘trots’. Apparently, even in severe cases, the administration of a clay–water mixture can be highly effective. The records of a Dr Julius Stumpf tell how he used kaolinite with great success to save his mother (and numerous other patients) during an

Pharmacopoeal preparation of kaolin. (Courtesy The Apothecary, Cairns, Australia) Front page image of Death bringing cholera, from Le Petit Journal, 1 December 1912. (Bibliothèque Nationale de France)

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Asian cholera epidemic in 1901 – the symptoms of diarrhoea, vomiting and cramping abated within a few hours of taking the remedy (Limpitlaw 2010; Reinbacher 2003).

Vibrio cholera. (Courtesy CDC, Public Health Image Library)

Waterborne transmission of cholera was first recognised in Europe in the mid-nineteenth century by John Snow and others. This sketch, ‘Death’s Dispensary’, was drawn by George Pinwell in 1866, around the time John Snow published his definitive studies. Untreated river water was responsible for the contaminated water supplies of London – similar to most other major European capitals. (Image courtesy CDC)

The antimicrobial properties of clay can extend to various forms of fungi. Aspergillus flavus is a common mould that infects stored food products and is a contaminant of water-damaged sites. This is the mould that grows on carpets following flood incursions. Exposure has been associated with serious lung infections (aspergillosis), with the potential to spread to other body systems, including the brain. In addition, many strains of Aspergillus flavus can produce aflatoxin, a highly toxic hepatocarcinogen

that is a contaminant of grains (notably corn, millet), oil seeds (particularly peanuts, almonds, Brazil and pistachio nuts), and dried fruit. Research has shown that clay (notably bentonite) had significant binding properties against aflatoxin in farmed animals. Therefore, it is not surprising that the use of smectite as an animal feed additive has a good protective effect against aflatoxin exposure, limiting its bioavailability (Mulder 2008; Phillips 1999, 1995). Research has subsequently focused on determining which type of clay is most effective and its suitability for use in food products to reduce human aflatoxin exposure (Jaynes & Zartman 2011; Phillips 2008; Tenorio Arvide 2008; Jaynes 2007).

Aspergillus sp. (Courtesy Janice Haney Carr, CDC)

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Ancient Legacies: Calcium and

Limestone

Calcite seabed, showing oyster shell remnants embedded in calcium carbonate. (Courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio).

Iron-stained calcite, with a reddish hue, perched atop an earlier generation of hematite-coated calcite. (Courtesy Rob Lavinksy, irocks.com) Milk of Magnesia and magnesium carbonate used as antacids. Early twentieth century, displayed at Herberton Historical Village, Queensland. (Courtesy Tony Young)

Calcite crystals inside a fossilised shell. (Courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio)

Ancient limestone deposit from southern Utah. The round grains are calcium carbonate ooids, small sedimentary grains that are formed on the sea floor. (Courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio)

Many antacid formulations are based on calcium or magnesium carbonate. Limestone is primarily composed of the shells of molluscs (and other creatures) mixed within a fine calcite (CaCO3) cement. Shells and pearls are good calcite resources, as are corals. Limestone is also a very good calcium resource that is often added to pet foods. Other mineral antacids have been sourced from dolomite (CaMgCO3) and magnesite (MgCO3). Nahcolite and trona are other natural sources of sodium carbonate with antacid potential that result from sea-water evaporation – and are commonly utilised as a baking soda resource (NaHCO3). Epsomite (MgSO4) is the source of the laxative Epsom salts. Magnesium sulphate also has emetic attributes and has been utilised as a poison antidote. In addition, a combination of epsomite with gypsum (alabaster) is effective for the relief of gastrooesophageal reflux (heartburn) that is associated with duodenal ulceration (Limpitlaw 2010).

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what their dimensions might be, but some were of enormous proportions and must have been quite a big job to execute. They were works of art, and produced a fine effect, and I imagine will be preserved in the future as a memento of the Great War’ (from Edward Fenton, Great Diaries from Around the World, Day Books).

Dolomite (calcium magnesium carbonate) from Limestone Gorge, Northern Territory. Dolomite has been used in horticulture as a soil conditioner, to lower acidity and provide magnesium. It is also used in marine aquariums to help buffer pH changes. (Image courtesy Craig Nieminski, flickr)

The Fovant Badges are military crests that were carved into the chalk hillside of Wiltshire, England, during World War I. They are currently scheduled as Ancient Monuments, although there continue to be problems with the long term maintenance of the sites. Of the eight surviving badges the largest is the Australian crest (pictured, 51 x 32 m), alongside those of British compatriots. Unfortunately the map of Australia, along with a number of other badges on the hillside, has faded into obscurity. (Image courtesy Fovant Badges Society, www.fovantbadges.com). The words of a timber merchant, Henry Peerless, in 1916 summarise the scene: ‘On our right hand side, behind the camps, was a range of hills, and we were attracted by a series of regimental crests on the side of these hills, most beautifully executed in, I think, white chalk. They varied considerably in size, and it is difficult to judge at a distance

Chalk, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841. Chalk is usually sourced from calcium carbonate deposits – which are resistant to weathering and quite porous. This allows them to hold good groundwater supplies, as well as sometimes forming spectacular environmental features.

A Dietary Detoxicant?

Clay appears to have been deliberately utilised to safeguard against the potential toxicity of unfamiliar or suspect food items for millennia. At times, it has been employed as an accompaniment to ‘famine foods’ (wild roots, bark, old seeds), some of which were known to have toxic properties (Abrahams 2005; Rowland 2002). There are some interesting

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investigations that support the detoxicant potential of clay against various chemical compounds. Clay has shown a high adsorption rate for alkaloids of various types – quinolizidine (sparteine, lupanine), tropane (atropine) and quinoline (quinine) – which was comparable to that of coal and charcoal. There were, however, differences in the efficacy of the clay. Quinine and atropine (lipophilic alkaloids) were more efficiently adsorbed than the water-soluble alkaloid lupanine (Mahaney 2000). This suggests that there is potential for a drug interaction problem with the use of clay as an antidiarrhoeal remedy. Studies from the Republic of Congo indicated that clay had a significant adsorption effect on chloroquine (around 60%) – which suggests that the concurrent use of both substances may compromise drug bioavailability in antimalarial therapy (Tsakala 1990). In addition to quinine, kaolin can significantly reduce the bioavailability of tannin-based drugs, that is, Quebracho (from the bark of Schinopsis balansae) and tannic acid. The adsorption level was significant (around 30%) in models resembling human digestive processes in the stomach and small intestine. Calcium oxalate, the main form of calcium present in plants, can also be rendered insoluble in the presence of kaolin (a precipitation level of 30% calcium was demonstrated) – which may therefore limit calcium bioavailability in some foods16 (Dominy 2004).   The use of clay for cooking purposes has been a traditional strategy for the detoxification of starchy tubers. The common potato (Solanum tuberosum) may contain variable levels of water-insoluble and heat-stable glycoalkaloids (notably solanine), which may not be detoxified during cooking. Some races of potato have much higher toxic potential that others (see Volume 3 for details). The use of clay to modify their toxicity is illustrated by the strategies of Native American tribes in the American southwest and nearby Mexico with regard to the tubers of Solanum jamesii and S. fendleri – which were similar to that utilised with acorn processing (see ‘Making Acorns Edible’. The consumption of clay with wild potatoes was specifically designed to eliminate bitterness 16 However, calcium oxalate can be an undesirable food component that is usually detoxified during cooking (heat exposure). This suggests that, under these circumstances, the use of clay may well be a useful detoxicant. Once again, it is a matter of bioavailability. Soluble and insoluble forms of calcium oxalate are discussed in detail in Volume 3.

 Bulrush: Typha

Aboriginal people utilised rhizomes of the Bulrush or Cumbungi cooked in earth ovens – with an intriguing use of clay balls (cricket-ball sized) as ‘heat retainers’. The entire process, however, was noted to be extremely labourintensive. A hole was dug, which was filled with firewood and the clay balls placed on top. These were then cooked and removed (still hot) when the fire died down. The hole was relined with moistened grass, upon which the Typha rhizomes were placed, covered with more moist grass, and the baked clay balls replaced on top. The earth oven was sealed with a soil covering to allow the food within to cook. The resultant starchy vegetable resembled a cooked potato. Inadequately prepared rhizomes retained purgative and emetic properties, which provided a good reason for being so careful with the cooking procedure (Rowland 2002; Gott 1999).

Bulrush.

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and thereby prevent stomach pain or vomiting. These types of side-effects are associated with glycoalkaloid overdose (Johns 1990, 1986). However, some clays appear to have a better detoxicant effect than others. Investigations of the effect of different clays on tomatine (a potato glycoalkaloid17) adsorption showed that kaolin clay was not as effective as bentonitebased clay, which had a substantial detoxicant effect. Interestingly, the Andean clay known as P’asa, in which smectite was predominant (mixed with some illite and quartz), showed a higher adsorptive capacity than either of these clays18 (Johns 1986).

Making Acorns Edible

Green acorn.

Mochica ceramic representation of the Potato, Larco Museum Collection, Lima, Peru. Eating specific types of clay with potatoes is an established practice in some cultures. The preparation of bitter potatoes in the Andes of South America involved dipping them in a thick slurry of clay before use. In the American southwest, where potatoes were eaten cooked and raw, the clay was added during cooking or taken with each mouthful of food. While alkaloids can be bound by clay, the degree of efficacy will not only depend on the digestive process, but the nature of the clay itself exerts a significant influence (Johns 1986). (Image courtesy Pattych, Wikimedia Commons, CC-by-SA 3.0 Unported) 17 Tomatine is present in numerous Solanaceae food plants, notably tomatoes. 18 Andean people clearly distinguish between clays that are edible and those used for practical purposes such as making pottery and preparing whitewash. They can name numerous different types of edible earth (kaolinite, illite, smectite) which show considerable variation in mineral composition. Other clay minerals with an outstanding ability to retain water are halloysite and montmorillonite (Rowland 2002).

Mortar holes ground into rock for leaching tannins out of acorns, at Lost Lake, California, near Friant. (Courtesy Wikimedia Commons, Public Domain)

The use of clay with food items as a detoxicant has been practised across the globe. In places as diverse as California and Sardinia, local people added clay to acorn meal – a strategy that removes the tannic acid (the levels of which can be quite high) by binding it to the

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clay particles. Investigations determined that tannic acid ingestion from cooked ‘acorn bread’ could be reduced substantially – as much as 77 per cent (48 mg/g acorn meal). There was not only a reduction in toxicity, the clay made the meal more palatable. Even so, the use of clay alone was unlikely to adsorb enough tannic acid to effectively deal with the toxic levels that would have been present.19 Prolonged heating would certainly contribute to the process of detoxification by enhancing a catalytic action of the clay. The interaction of tannic acid with iron or aluminium is another factor that contributes to the detoxification process. There are potential nutritional benefits for clay use, depending on the bioavailability of the mineral components. Acorn–clay combinations showed that calcium was bioavailable in Sardinian clay (2.1 mg/g, i.e. 37% total calcium) and Californian clay (0.71 mg/g). In African clay samples, calcium was generally less bioavailable, with the exception of one sample from Kenya. The situation with other minerals was similar, with different locations showing variable bioavailability for specific minerals (%RDA, recommended daily allowance, country): iron (100%, Zaire), manganese (100%, Kenya, Zambia), copper (15%, Kenya, Nigeria, Kenya), calcium (15%, Kenya), zinc (5–7.5%, all African clays sampled), magnesium (8–10%, Kenya) (Johns & Duquette 1991a, 1991b). Other studies have given similar results. Therefore, while clay minerals can be present at appreciable levels, their bioavailability will ultimately determine their dietary usefulness. Certainly, in times of nutritional deficiency, some clays could have value as a mineral supplement.

19 California clay showed 5.6–23.7 mg/g tannic acid sorption. Under optimal conditions 1 g of clay could therefore adsorb 23.7 mg tannic acid from 10 acorns. Sardinian adsorption (clay:acorn ratio 1:8) would be 13.5 mg (around 8% total tannic acid). In practical terms, sorption is affected by pH, ionic strength and competing adsorbents. During processing (cooking) and digestion the sorption level is likely to be less than the maximum level proposed (Johns & Duguette 1991a).

In the 1530s, during his travels in the southeast of the United States, the explorer Álvar Núñez Cabeza de Vaca observed that the fruit of the Mesquite tree (Prosopis juliflora) was eaten with soil by the Native Americans – a combination that was said to make the fruit sweet and palatable (Abrahams 2005). Mesquite is a leguminous tree, the pods of which have been utilised as a flour resource. However, ‘Mesquite’ can refer to a number of Prosopis species. These are drought-tolerant plants with an invasive habit and Prosopis pallida (pictured) has been listed as a Weed of National Significance in Australia. (Images courtesy Kim & Forest Starr, Hawaii)

EARTH MEDICINE: A MINERAL PHARMACY

  Avian Geophagy

Young chimpanzees in the Jane Goodall Tchimpounga Sanctuary, Republic of Congo. Observations of the eating habits of chimpanzees in Uganda found that they ate clay just before or after eating the leaves of Trichilia rubescens. Although the reason for this behaviour remains open to debate, the leaves of this plant contain limonoids with effective antimalarial activity (Krief 2004, 2006). Investigations showed that the soil-eating habit enhanced the pharmacological effects of Trichilia during the digestive process – which suggests that the clay could promote the antimalarial properties of the herb. In addition, it is of interest to note that local healers have utilised the same type of kaolinite-based soil as an antidiarrhoeal agent, which was considered particularly useful for bloody diarrhoea. Phytolacca dodecandra fruit, which contains saponins, has been similarly eaten with a clay accompaniment by chimpanzees. Whether this has any bearing on the usefulness of the latter herb is the subject of further study (Klein 2008). (Image courtesy Delphine Bruyere, Wikimedia Commons, CC-by-SA 3.0 Unported)

Phytolacca dodecandra fruit. (Courtesy Stefan Gara)

The Green-winged or Red-and-green Macaw (Ara chloropterus) is one of the clay-eating bird species of Peru. (Courtesy Michael Gwyther-Jones, Wikimedia Commons, CC-by-SA 2.0)

The habit seen in some birds (parrots, macaws and parakeets) of eating certain types of clay first attracted scientific attention in 1999 when it was observed in 11 species from Papua New Guinea. The parrots tended to eat earth when their diet had a high content of unripe seeds and fruit – a situation that would increase the toxic component of their diet. The adsorptive effects of clay minerals were suggested as a means whereby they could reduce the risk of poisoning. Investigations tend to confirm this hypothesis. Brine shrimp were exposed to the seed toxins found in the parrots’ diet and the clay additive significantly reduced the toxic effects. In addition, investigations of alkaloid (quinidine) exposure in parrots showed significant reductions (blood levels reduced by 60%) when clay was added to the mixture (Abrahams 2005; Gilardi 1999).

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The clay chosen by the birds is specific. Smectite-based clay had the highest quininebinding potential, which was 25 times greater than that of micas or kaolinites – a difference in toxin binding capacity that could vary by up to 300 per cent20 (Gilardi 1999). Subsequent studies of clay ‘licks’ used by eight bird species in Peru showed that the fine-textured clay had a high cation exchange capacity, which would facilitate toxin binding – as well as having a beneficial gastrointestinal protective effect. Moreover, this clay appears to be an important sodium resource, a mineral that is normally only present in low levels in the local plant foods. Surprisingly, the sodium availability from the clay was 40 times higher than from average plant sources. The clay did not, however, appear to be as useful for other minerals (calcium, potassium, magnesium, manganese and copper) which were present at levels comparable to, or less than, those in the local plants. Even though iron levels in clay could be around twice that of the vegetation, around 10 per cent of the flora also had a substantial iron component. Plant resources contained about 100 times more potassium (Brightsmith 2008).

Blue-and-yellow Macaws, Scarlet Macaws, Mealy Amazons and Chestnut-fronted Macaws at the clay lick at Tambopata National Reserve, Peru. (Courtesy Brian Ralphs, Wikimedia Commons, CC-by-SA 2.0) 20 Experimentally, each gram of smectite-clay bound 20 g of quinine, with the best soil type binding 40 mg/g quinine. Amazonia parrots that were given 50 mg of quinidine (a less toxic alkaloid) and 2 g clay showed a reduction in quinidine absorption by 60 per cent (i.e. the soil adsorbed 15 mg/kg) (Gilardi 1999).

Young Rhesus Macaque (Macaca mulatta). An analysis of the soils from Kowloon, Hong Kong that were eaten by hybrid Macaques found they usually favoured fine-textured soils that were higher in iron and aluminium oxides. Magnesium levels could also be high (Bolton 1998). (Image courtesy Jack Hynes, flickr)

Neotropical fruit bats, Artibeus sp., in Tortuguero National Park, Costa Rica. Research into the reasons for fruit bats in the Amazon rainforest visiting mineral ‘licks’ has concluded that pregnant and/or lactating females did not visit these sites for mineral resources but used the clay minerals to ‘buffer the effects of secondary plant compounds that they ingest in large quantities during periods of high energy demand’. This greater dietary diversity increased the potential for exposure to toxic compounds – and it would appear that clay is being utilised as a detoxicant component of the diet (Voigt 2011). (Image courtesy Wikimedia Commons user Leyo, CC-by-SA)

EARTH MEDICINE: A MINERAL PHARMACY

Drug–Clay Interactions

Processed clay minerals. (Courtesy Volker Thies)

The presence of clay in the gastrointestinal tract can alter drug bioavailability. Clay can influence its liberation and stability – thereby affecting drug release, its absorption and, ultimately, its efficacy. The consequent alteration in blood levels can therefore influence a drug’s clinical value. This action occurs because clay minerals carrying a negative charge will absorb protons. Digoxin can be used to illustrate the point. This important cardiovascular drug is affected by hydrolysis, a process catalysed by acid in the presence of the clay mineral montmorillonite. In the stomach, the acid level (pH 2) allows digoxin to degrade by 20 per cent per hour – whereas in the presence of montmorillonite it will be completely degraded within the hour.21 Digoxin would therefore lose its therapeutic value because adequate blood levels are not maintained (Porubcan 1979). Anti-inflammatory drugs such as dexamethasone and hydrocortisone are similarly affected by the presence of clay minerals such as palygorskite and sepiolite. More rapid degradation can occur with palygorskite due to its iron content – which acts as a catalyst, making the drug reaction occur more quickly (Carretero 2002). The issue of clay minerals and their effect on drug absorption is an interesting topic that has only fairly recently been evaluated with a view to innovative developments in drug delivery systems. The use of clay as an excipient22 can be quite handy when a 21 Drugs are designed to be maintained at a therapeutic dose in the blood for a predetermined period of time. Those that tend to degrade in the presence of protons will do so more rapidly upon exposure to clay in the stomach. This can occur even if they have not been administered at the same time – and may well compromise the efficacy of the drug treatment.

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slow-release strategy is desirable. Early studies have shown that the excretion of amphetamine sulphate in the urine was significantly reduced when it was absorbed in montmorillonite. This allowed the drug to maintain therapeutic levels in the blood for a longer period (McGinity & Lach 1977). The antibiotic clindamycin, which can form a complex with the same mineral, is highly adsorbed by clay in the stomach. Upon encountering changes in pH in the intestine it is then slowly desorbed and released – permitting a prolonged effect (Porubcan 1978). It is this slow-release effect of clay minerals that has been most useful therapeutically. Palygorskite, the smectites, kaolinite and talc, can therefore be used as excipients to change the physical properties of the drug delivery process (see Table 5.1; also Aguzzi 2007 for further detailed information on innovative claybased drug-release strategies).

Montmorillonite, from Minerals in Your World project. (Courtesy US Geological Survey & Mineral Information Institute)

Clay minerals have been utilised for other drug release strategies – as lubricants in pill manufacture (i.e. talc), as water-retentive tablet disintegrants (e.g. smectites) that swell and release the active drug component, or as tablet dispersants (i.e. palygorskite) that liberate a drug on contact with stomach acid. They can also provide inert bases for cosmetics, and can act as emulsifying, gelling or thickening agents. All these properties make them very useful for pharmaceutical 22 Excipients are additives used in the drug formulation for a specific purpose, with the aim of maximising the drug delivery process. Excipients act via decreasing or increasing the dissolution rate, delaying drug release, improving drug targeting, preventing or reducing side-effects, improving taste, or increasing drug stability (Viseras 2010).

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Table 5.1 Summary of Clay Types Used in Pharmacy and Drug Delivery Systems

(Based on Lopez-Calindo 2007; additional information on drug interactions as cited) Clay is a generalist term referring to a very finegrained mineral material that acquires plastic qualities on combination with water and hardens upon drying. The term ‘clay minerals’, however, has a more specific mineralogical meaning, referring to part of a family (phyllosilicates) that contain hydrated aluminosilicates with considerable amounts of Mg, K, Ca, Na and Fe, with some less common ions (tin, manganese or lithium). While all clay mineral types can have a variable chemical composition (see Lopez-Galindo 2007), processing is undertaken to remove undesirable components such as asbestos (tremolite) and carbon from talc. Furthermore, the use of a clay mineral for a specific purpose not only depends on its chemical composition, but the type of structure (1:1 or 2:1 layer type) significantly influences the cation exchange capacity. Textural differences, even between minerals that are structurally and chemically identical, will also affect absorptive properties and rheological (flow) qualities (Lopez-Galindo 2007). It is important to note the following differences in terminology (Viseras 2010, 2007): Kaolin, from British Pharmaceutical Codex, 1934.

purposes. Clay minerals (notably kaolinite, talc and smectites) have a high absorbency capability, with an ability to adhere to grease, toxins, bacteria etc., making them useful for inflammatory and infective skin problems (acne, boils, ulceration). For example, talc and kaolinite can be used as skin protectants and adsorbents to carry antibiotic, analgesic or antihistamine agents which are released on skin contact. The use of clay components in water-resistant sunscreen formulations is similar. Sepiolite and smectites can combine with compounds that absorb UV light, thereby enhancing the protection factor of a formulation. Some combinations can retard its dissolution in salt water, allowing longer sunscreen protection (Carretero 2002). The multitudinous applications of clay minerals, in this respect, are formidable.

• Th  e pharmaceutical name of the smectites (montmorillonite and saponite) is magnesium aluminium silicate in the USA or aluminium magnesium silicate (AMS) in Europe. Bentonite is a colloidal hydrated aluminium •  silicate montmorillonite-based clay. • Talc is hydrated magnesium silicate, while kaolin is hydrated aluminium silicate. • Activated attapulgite is heat-treated magnesium aluminium silicate.

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Table 5.1 Summary of Clay Types Used in Pharmacy and Drug Delivery Systems Classification: Clay mineral Official product Kaolin group Kaolinite (most common, i.e. ‘white clay’); halloysite Official product: Kaolin is a purified, natural hydrated aluminium silicate of variable composition

Qualities Kaolinite: • White/greyish white; becomes darker and more plastic when moistened with water. • Characteristic earthy taste, clay-like odour when wet. • Low cation-exchange capacity. • Variable chemical and physical properties. • Relatively low specific surface area, but capable of adsorbing small molecular substances, protein, bacteria, viruses in the surface of particles that are easily removed.

Drug uses: potential side-effects and use in enhanced drug-delivery systems Reduce drug absorption: Kaolinite will affect amoxicillin, ampicillin, atropine, cimetidine, clindamycin, digoxin, phenytoin, quinidine, tetracycline (Lopez-Calindo 2007).

Drug-release systems: •  Halloysite: used to retain mesalazine (antiinflammatory) for treatment of inflammatory bowel disease in slow-release system (Viseras 2010). •  Halloysite: prolonged release rate for propranolol (antihypertensive) (Aguzzi 2007). •  Halloysite with diltiazem (antihypertensive) plus polymer coating (incl. chitosan) to reduce dissolution rate (Aguzzi 2007). Talc Often utilised as a skin dusting agent or cosmetic Pure talc: additive that is suitable as a carrier for antibiotic, • Translucent, white/near-white. Official product: • Odourless, flaky habit and easily milled to analgesic or antihistamine agents (Carretero 2002). Talc is purified, powdered, become a bright white unctuous powder. selected natural hydrated •  Mineral qualities vary with type of talc and the processing method can alter its effects, e.g. Drug delivery systems: magnesium silicate hiding powder, wettability. Hydrotalcite: used to prepare extended release •  Mineral composition, which can vary formulations of anti-inflammatory agents significantly from site to site, can have enormous (ibuprofen, diclofenac) (Aguzzi 2007). influence on potential uses. • Very good absorption capacity for oil and grease. •  Plastic, colloidal swelling clay composed of Adsorbent activity: Bentonite •  smectite. Smectites adsorb to amphetamine sulphate, Smectite-based clay tetracycline, tolbutamide, warfarin sodium, (mainly montmorillonite, • High cation exchange capacity (this influences diazepam. drug retention capacity). also saponite); ‘green clay’ • Differences in origin or chemical composition • Smectites can retain large amounts of a drug can influence technical properties; however very (Lopez-Calindo 2007). Official product: Bentonite is a natural pure (>95% smectite) deposits are common. Controlled drug-release systems: clay containing a • Smectites feel greasy and soap-like, odourless, • Ibuprofen (anti-inflammatory) combined with high proportion of slightly earthy taste. montmorillonite to retard drug release. drug) with montmorillonite (a native • Great colour variation: white, yellow, pink, grey, •  Donepezil (Alzheimer’s pale green. montmorillonite, saponite or laponite. hydrated aluminium • Commercial products: fine-grained powder; • Montmorillonite plus polylactic glycolic acid: silicate may also contain nanoparticles loaded with docetaxel (anticancer magnesium and iron) purified bentonite is colloidal montmorillonite drug) for prolonged release over 25 days and purified to remove grit and non-swellable ore enhanced uptake by cancer cells. Note: Fuller’s earth is a components. mixture of clays with a • Ability to form thixotropic gels with water, can • Montmorillonite combined with polyethylene high magnesium oxide absorb large quantities of water (12–15x volume glycol has been used for controlled release content. It is usually increase). of paracetamol: improved dissolution of drug from the smectite group • Bentonite magma: 50 g bentonite with 1000 g with slower drug diffusion. (notably montmorillonite), purified water. •  Nicotine: use of magnesium aluminium although attapulgite may (MgAl) silicate to reduce drug evaporation and be present in some clay modulate drug release. varieties. •  MgAl silicate with sodium alginate: used to prepare films for buccal release systems: improved adhesion properties in mouth allowing controlled drug release. • Propranolol (β-blocker) combined with MgAl silicate. •  Montmorillonite plus chitosan also used for prolonged release and biomedical applications (Viseras 2010). • Montmorillonite–lidocaine (anaesthetic):  extended duration of activity (Aguzzi 2007).

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Clay minerals: May influence bioavailability: • Fine white-coloured powders that are free from •  Palygorskite: decrease bioavailability of any gritty quality. loperamide and riboflavin. • Odourless and tasteless. •  Magnesium trisilicate (sepiolite): decrease Official product: • Variable water absorption: palygorskite 5–27%; bioavailability of mebeverine hydrochloride, Attapulgite: purified native sepiolite 17–34%. proguanil, norfloxacin, sucralfate, tetracycline; hydrated magnesium • Purity: natural sepiolite deposits can be very pure may also retard dissolution rate of folic acid or aluminium silicate (95%); palygorskite less so (75%). paracetamol (Lopez-Calindo 2007). (palygorskite) Sepiolite: magnesium Activated attapulgite: palygorskite heated to Absorption decreased: trisilicate (a blend of Si increase adsorptive capacity; a high heat-drying • Anti-diarrhoea mixtures containing attapulgite and Mg oxides) process removes water to enhance absorbent decreased promazine (antidepressant) qualities: micronised fibre lattices trap liquids to absorption. make high viscosity suspensions. •  Sepiolite: controlled release of antifungal and antibacterial isothiocyanates for sanitary Magnesium trisilicate: pharmacopoeal requirements protection in kitchens and food preservation can differ (minimum requirement % w/w): United (Aguzzi 2007). States Pharmacopoeia (USP 2006) 20% MgO, 45% SiO; European Pharmacopoeia (EP 2002) 29% MgO, 65% SiO Fibrous clays Palygorskite (attapulgite) and sepiolite

Note: There is also a special hectorite clay (including a synthetic hectorite, sodium magnesium silicate) that is used for cosmetic purposes, as well as specially modified clays (modified bentonites and modified hectorites) (see Viseras 2010, 2007 for details).

Petrified Forest National Park, Arizona, showing bands of pastel colours in the Blue Mesa. The bands indicate environmental conditions at the time the sediment was deposited. Blues and greys originate from carbon decaying in organic material that remained unexposed to air (buried or under water). Reds result from hematite (an iron-based material) – on exposure to air, even a small amount of iron can cause the rocks to oxidise (rust). The whites represent nearly pure bentonite clay. Ground water, percolating through the buried sediments, has also contributed to some colour changes. (Image courtesy Ritchie Diesterheft, flickr. com/photos/puroticorico)

Talc. (Courtesy Eurico Zimbres CC-by-SA 2.0)

  Gypsum and Alabaster

In Chinese medicine gypsum is known as Shi Gao (‘stone paste’). The Reverend BE Read (1928) noted: ‘As bought in the drug shops it is in powder, which when moistened and then allowed to dry forms a hard mass’. It has been traditionally valued for treating feverish and full-heat conditions, with symptoms of high fever (without chills), irritability, thirst, profuse sweating – as well as lung disorders (cough and wheezing), stomach distress (swollen, painful

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Gypsum sand. White Sands National Monument, New Mexico. Gypsum (calcium sulphate dihydrate) is a very soft form of calcium from which alabaster items were carved in Ancient Egypt. (Image courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio)

Ancient Egyptian alabaster jar, Cairo Museum.

Selenite gypsum, from Minerals in Your World project. (Courtesy US Geological Survey & Mineral Information Institute)

Contaminant Considerations

There are a couple of contamination issues with regard to soil that require consideration. In particular the contamination of clay with domestic waste or toxic minerals has the potential for serious health consequences. In the past, children have suffered lead poisoning due to eating foreign objects (dirt, plaster, newspaper etc.) (Halsted 1968). Recently, in the United Kingdom, samples of the geophagic material known as ‘Calabash chalk’, popular in West African and Nigerian immigrant communities, were found to contain dangerous levels of lead, particularly for pregnant women who traditionally

with headache), toothache and heat-type skin problems (eczema, burns, ulcerated sores) (Bensky & Gamble 1986). In Australia mention was also made in 1908 ‘of the medicinal employment of earth, ashes, and sand; women rub their breasts with a pap made of gypsum for the purpose of causing a secretion of milk’ (E Eylmann, Die Eingeborenen der Kolonie Sudaustralien, 1908, p. 448, quoted in Laufer 1930).

utilised it as a remedy during pregnancy, probably to ease gastrointestinal discomfort. Its importation was subsequently banned (Abrahams 2006). There is a risk of increased exposure to cadmium and arsenic with some soils, notably those from Bangladesh where arsenic contamination of the groundwater supplies is a serious issue. Studies have found that these compounds could be present in a bioavailable form. The fact that high concentrations of cadmium have been found in the breast milk of women in Bangladesh suggests serious environmental contamination issues with regard to food supplies (vegetables and rice) that could be compounded by

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the habit of sikor (clay) ingestion. Indeed, merely 50 g of clay could raise the levels of arsenic and lead by 3and 6-fold, respectively, over the maximum tolerable daily intake – a significant cause for concern (AlRmalli 2010). Chronic low-level arsenic exposure, which also resembles lead poisoning, can be difficult to diagnose. The symptoms can be mild and insidious, with progressive disability developing in just about every system in the body: chronic fatigue with anaemia, gastrointestinal discomfort, liver dysfunction, neurological problems (polyneuritis), immune system dysfunction, hair loss, nails falling out, and a characteristic skin condition (hyperpigmentation, eczema) developing. Acute poisoning is associated with severe gastrointestinal distress, dizziness, delirium, coma, and often convulsions. This can result in circulatory collapse, renal and hepatic failure, and blood disorders. High levels of arsenic have been linked to an increased incidence of cancer (particularly skin melanoma), heart disease, stroke, chronic respiratory disorders and diabetes.

  Arsenic: A Ubiquitous Toxin

red arsenic sulphide mineral, will impart a pink hue. Orpiment is another, gold-orange, arsenicbased mineral that is associated with volcanic activity and hot springs. It has been estimated that over 137 million people, in 70 countries, may be affected by arsenic poisoning – which is commonly encountered as a groundwater contaminant. The type of arsenic is important. The arsenic oxides, which readily dissolve in water, have particularly high toxic potential. Indeed, arsenic trioxide, which is 500 times more toxic than pure arsenic, may be naturally present in groundwater. Arsenic oxides (arsenites) are also a common by-product of ore processing. Landscapes with a long history of mining and smelting can have high residual soil levels of arsenic, copper, fluorine and lead – which can enter the food chain via livestock feed, or as a contaminant of crops. Arsenic poisoning has occasionally been linked to home-grown vegetables on land reclaimed from former mine dumps in the southwest of England. However, individuals exposed to low levels for a long period of time appear to develop a measure of tolerance to arsenic. Interestingly, soil iron has a protective effect as it can lower the bioavailability of arsenic to vegetable crops (Abrahams 2002). Another ubiquitous source of environmental contamination has resulted from the continued use of arsenates in the production of chromated copper arsenate (CCA) for timber treatments, arsenic-based pesticides, glass production, pharmaceuticals and non-ferrous alloys.

Arsenolite, from White Caps Mine, Nevada, USA. (Courtesy Rob Lavinsky, irocks.com)

The term arsenate (AsO4) refers to any compound that contains the arsenic ion – and many minerals fall into this classification. Arsenolite and claudetite are the main arsenic (arsenite)-based minerals that are formed from oxidation of arsenic sulphides. They are white in colour, although this may change if impurities are present – for example, realgar, an orange-

CCA-treated timber.

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Lead Poisoning

Garlic can have a significant detoxicant effect on arsenic. Preliminary investigations have shown that an aqueous (water) extract of garlic had a strong antioxidant and chelating efficacy, and/or oxidising capability that acted to reduce the toxicity of arsenic by altering trivalent arsenic into a pentavalent form (Chowdhury 2008). Thus the regular use of garlic in the diet could well have anti-toxin benefits that have hitherto remained unappreciated.

Lead ingots from Roman Britain, on display at the Wells and Mendip Museum. (Courtesy Rod Ward) Lead pipe in Roman bath in Bath, Somerset, England. (Courtesy Stan Zurek, CC-by-SA 3.0 Wikimedia Commons)

Solution of Subacetate of Lead or Goulard’s Extract (solution of diacetate of lead) consisted of acetic acid:protoxide of lead (1:2). This was primarily utilised, in a highly diluted form, for inflammatory skin disorders and fungal nail infections. Albeit rarely taken internally, there were some rather disturbing recommendations (for toxicological reasons) that mentioned its use as an enema for rectal discharges (including dysentery and cholera), and topically for leucorrhoea (vaginal discharge) and gonorrhoea. It was also employed as local irrigation for ENT (ear, nose and throat) disorders, as a mouthwash and gargle (Wood 1867). (Image from Herberton Historical Village, Atherton Tablelands, north Queensland) Iron can be an effluent contaminant of water supplies. This image shows acid drainage from surface coal mining, with iron hydroxide precipitate staining the water orange. (Image courtesy D. Hardesty, USGS, Columbia Environmental Research Center)

The presence of lead as a toxic contaminant of earth warrants particular attention due to the significant health repercussions, particularly for children in urban or industrial areas.

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In some places the soil is lead-rich due to the natural weathering of mineral deposits, whereas in other areas old mine workings are responsible. Leaded petrol and paint have left a remarkable level of residual contamination in the environment, particularly in urban soils (gardens, school playgrounds, parks) – which can contain numerous other compounds at toxic levels, including cadmium and zinc. The lead at these sites may even be more hazardous than that normally found in mineral deposits (pyromorphite) due to increased solubility (i.e. chloride- or bromide-based forms of lead). Even small amounts of lead exposure have been associated with behavioural problems, poor growth and development, and impairment of intelligence (Abrahams 2006, 2005). Lead poisoning has resulted from a geophagic habit (eating earth or clay). In one case where garden soil was involved, the clinical picture showed anaemia and seizures, which improved with chelation therapy. However, a resumption of the habit exacerbated the kidney failure (lead nephropathy) that had already occurred (Wedeen 1978). Other symptoms of lead poisoning in adults include hypertension and peripheral neuropathy (Hardy 2002). Children are more sensitive to lead exposure. Adults absorb 5–15 per cent of ingested lead, retaining only about 5 per cent of the amount absorbed. However, the bioavailability for children is much higher: they can absorb up 41 per cent of ingested lead, with 90 per cent of this being bound to haemoglobin in red blood cells. This is redistributed to soft tissues and is ultimately deposited in bone – with a half-life of over 20 years, resulting in hazardous long-term exposure. During pregnancy lead can be mobilised from the mother’s bone – and can cross the placenta and cord blood. Lactation is another problematic route of exposure. Infants and children are at particular risk of neurological toxicity and damage to brain function23 (Hardy 2002, 1998). Recently, studies have suggested a strong association between the prevalence of leaded petrol in the environment and violent crime. This rather frightening scenario may well find links between other forms of lead exposure and serious behavioural

The brain is the most sensitive part of the body with regard to lead exposure. This image shows brain damage (red and yellow clusters) due to childhood lead exposure: midline of left and right hemispheres (row 1); back and front of the cerebrum (row 2); lateral right and left hemispheres (row 3): below and above the cerebrum (row 4). (Image courtesy KM Cecil 2008)

problems in children. In Australia concerns have been expressed with regard to lead contamination of water from old pipes, living near mines or smelters, and occupational exposure (electronic equipment and plastics manufacture, battery recycling, glazes for pottery, jewellery making, alloys and 23 The traditional use of kohl as a sealant on the umbilical cord of the newborn is a significant risk factor in Egypt. The use of leadcontaminated kohl makeup has been identified in some Arabian Gulf and northern African countries as equally problematic (particularly for schoolgirls) as it is very bioavailable through the conjunctiva of the eye. Lead may also be a contaminant of traditional medicines (Hardy 2004, 2002).

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casting work, renovation jobs). Hand to mouth (particularly sucking dirty fingers) has been the major means of contact for many children, and occupational exposure can be quite high in adults. The risk of exposure should not be underestimated. There are many avenues of entry into the home from lead-contaminated environments – dust on and inside cars, clothing, mobile phones, bags etc. Personal hygiene is extremely important – that is, washing the hair and nails before touching infants or children – and clothing should be washed separately from any unexposed materials. Blood levels should be below 10 mcg per decilitre, whereas high exposure can result in levels of 70–100 mcg/ decilitre.24

Blood film showing anaemia due to lead poisoning in cells on the far left and right (blue/purple dotting) and centrally (faded purple with irregular cell edges). (From Herbert L Fred & Hendrik van Dijk, Images of Memorable Cases – 50 years at the Bedside, Rice University Press, Houston, TX, 2007)

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pelvic area, upper and lower extremities). In 1968 in Toyama Prefecture, Japan, an outbreak was linked to cadmium-contaminated rice as the primary cause, although drinking water supplies were also suspect. The source of the problem was traced to the Kamioka Mine releasing cadmium waste into river water that was used to irrigate rice paddies. As rice is a staple part of the diet, exposure levels could be quite high. In addition, malnutrition appears to have contributedto the severity of the condition (Abrahams 2002). Recent investigations reviewed in the USA Consumer Reports have shown many rice products

Soil acidification will enhance the uptake of cadmium by vegetables such as lettuce and cabbage grown on contaminated sites.

24 See www.nhmrc.gov.au/guidelines/publications/gp2-gp3.

Excessive cadmium levels are an equally problematic matter of concern in many urban and agricultural environments. Cadmium can be a contaminant of sewage sludge, phosphate-based fertilisers and industrial emissions. In the 1960s, cadmium exposure was linked to the occurrence of a devastating form of osteomalacia (significant bone softening, with associated skeletal degeneration) and severe kidney damage. Known by the Japanese name of itai-itai (‘ouch-ouch’, referring to the painful nature of the condition), it primarily affected women, who experienced severe joint and bone pain (breast,

Terraced rice paddies. Soils with even relatively low cadmium concentrations can be problematic. The cadmium is made bioavailable due to acidic character of the soil (pH 5.1) – as well as low carbonate and low hydrous oxide soil components, particularly in rice paddies. The bioavailability of soluble cadmium was found to be around 4 per cent in rice paddies. In comparison, in high-cadmium soils at Shipham in the United Kingdom the level was 0.04 per cent. The latter was characterised by free-draining soils with a higher sorption capacity: high pH 7.5–7.8,and high CaCO, and high hydrous oxide levels (Abrahams 2002). .

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contain significant arsenic levels, particularly rice cereals and brown rice – as well as apple and grape juices. The implications could be quite worrying for children’s snacks and baby foods (Consumer Reports Magazine February & November 2012) – although there does not appear to be any current evidence of contamination with regard to Australian-grown products (http://www.consumerreports.org/cro/ magazine/2012/11/arsenic-in-your-food/index.htm). Other soil-based minerals with toxic potential include silver, beryllium and mercury, and various radioactive isotopes. Indeed, white clay (kaolinite) and green clay (bentonite) can contain levels of radionuclides that would advise caution in their ingestion. The level in green clay tends to be higher, and suggestions have been made that merely ingesting 1 g per day can represent 6–10 per cent of the annual allowable dose, which is 1 millisievert (mSv) (Silva 2011). Inhaled radon is another radioactive material with detrimental potential for human health. This gaseous breakdown product of radioactive minerals (uranium, thorium) can diffuse through rock and soil to escape into the atmosphere. Unfortunately, radon has been found as a contaminant in urban households in areas where naturally high ground levels of radioactive compounds occur. This gas can be drawn from the earth due to a pressure difference between the house and the soil underneath, resulting in unexpectedly high levels in urban settings. Radon

Radon test kit. Radon is not the only natural product with a gaseous character that can give rise to environmental concerns. Wetlands have the potential to be a problematic source of methyl halides (CH3Br, CH3Cl). Even more concerning is the fact that the pesticide CH3Br (methyl bromide), which has been manufactured for widespread use as a soil fumigant gas, is easily released back into the atmosphere. It is now listed among the most important causes of ozone destruction, rating just below CFCs and halons (Abrahams 2002). (Image courtesy US Government, NIH)

exposure is an important contributing factor to lung cancer and myeloid leukaemia, as well as other cancers. Contamination occurs not by the action of radon itself – but because its breakdown products (polonium isotopes) adhere to dust particles, which are then inhaled (Abrahams 2002).

Toxic pesticide warning sign. (Courtesy Colin Grey, Wikimedia Commons, CC-by-SA 3.0 Unported)

Crop dusting: biplane spraying pesticide in 1947. Despite the fact that the spray was dispersed from the rear of the plane, pesticide exposure was still a risk for the pilot – not to mention those on the ground. There was not only the problem of potential exposure to the toxin during spraying. Quite high levels of exposure could easily occur during its formulation – and later, when cleaning the spray tanks. (Photograph by Dick Robbins, courtesy US Centers for Disease Control, National Institute for Occupational Safety and Health)

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Various other minerals of interest are usually only found as trace elements, although in excess their presence can be problematic. In addition to iron and zinc, they include chromium, cobalt, copper, fluorine, iodine, manganese, molybdenum and selenium. (Soils that are deficient in fluorine, iron, iodine and selenium have also been associated with serious health problems.) • Molybdenum: poorly drained soils with a neutral/ alkaline character can result in an increased intake. Very high levels appear to be associated with a prevalence of gout in Armenia. Exposure (high levels) may also reduce the incidence of dental caries – although a dietary deficiency from staple crops (maize, beans, pumpkins) in South Africa has been linked to a high incidence of oesophageal cancer. • Iodine: soils that are deficient in this element are relatively common across the globe.25 A high pH and a high organic matter component tend to reduce iodine availability, retaining it in a non-bioavailable form. Goitre (enlargement of the thyroid gland) is the most prevalent symptom of deficiency, although there can be numerous associated problems: stillbirth, abortion, congenital abnormalities, endemic cretinism (mental deficiency, deaf-mutism,

Some dietary components (goitrogens) can block the utilisation of iodine, resulting in the development of goitre. Thiocyanate release from inadequately prepared cassava (pictured) can act as a goitrogen.

spastic diplegia), diverse neurological disorders and impaired mental function. • Selenium: A deficiency of soil selenium in locally grown cereal and vegetable crops can result in low dietary levels. Significant reductions in selenium bioavailability, even in high-selenium soils, occur when the soil has a high pH (70° C) in Fiji, where the sediment remains undisturbed. The white blobs are gas bubbles, which can be made to rise by merely clapping the hands – while the yellow is a type of lichen. To live in an environment like this, the lichen must have some remarkable heat-tolerant properties. (Image courtesy Ian Mackay)

A DESIRE FOR DIRT?

conditions (see also ‘Shilajit: Therapeutic Humus’, page 260). In parts of Europe old peat spas from the eighteenth century are still in use. Various studies have shown that balneotherapy can be associated with increased pain relief, particularly in rheumatological conditions (Falagas 2009; Deniz 2002; Verhagen 1997, 2004). Sapropels, which are permanently inundated silted deposits from water reservoirs (bogs, riverine and marine environments), have been utilised similarly. They contain a large amount of organic matter (notably humic and fulvic acids) in a colloidal state, whereas in peat the plant matter has been humified in a marshy environment under conditions of high humidity, resulting in an increased level of solidification6 (Schepetkin 2002).

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In addition to its use as a spa additive, peat has been shown to have antioxidant, antibacterial, antiinflammatory, circulatory supportive, antiulcer and healing attributes. It has been utilised in a distilled and sterilised injectable form (the Russian product Torfot) for inflammatory mouth (stomatitis) and eye disorders (keratitis, chorioretinitis), to protect against degeneration of the retina, to heal pulmonary tuberculosis, and for diverse other chronic inflammatory disorders. Similar recommendations have been made for a Polish product (TPP: Tolpa Peat Preparation) as an immune-stimulant, antiinflammatory agent – and for a number of commercial sapropel products (Schepetkin 2002): •  Peloidodistillate (Caucasian region, Russia): degenerative eye disorders, neuralgia, gynaecological inflammation. •  Humisol (Tallin, Estonia): immune disorders, arthritis, respiratory tract infections. • Peloidin (Odessa, Black Sea mud): gastrointestinal ulceration, biliary tract disorders, lumbar osteochondrosis, genital inflammatory disorders. •  FiBS (a specific type of sea mud): immunomodulatory and anti-allergic properties. • Eplir (oil solution prepared from lipid fraction of a specific sulphide mud): antioxidant with significant hepatoprotective properties.

Cobar Red Clay bath salts. (Courtesy Claire Maraju, Australian Native Therapies)

A peat stack in Ness on the Isle of Lewis, Outer Hebrides, Scotland. Peat is a brown-black organic sediment that forms in water-saturated sites resulting from the partial decomposition of mosses, ferns, sedges, grasses, shrubs and trees. (Image courtesy Maclomhair, Wikimedia Commons, CC-by-SA 3.0 Unported)

Mud therapy, Fijian Islands (Viti Levu). (Courtesy Ian and Sue Mackay)

6 Peat and mumie (shilajit) have been exposed to a higher oxygen influence than sapropel. This results in an intensification of oxidation processes, as well as changes in chemical and biological characteristics of the humic and fulvic acid components. Additionally, the composition of these acids in the organic–mineral matter will vary according to geographic location, and consequent vegetation differences (Schepetkin 2002).

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  Shilajit: Therapeutic Humus

Shilajit (also known as mumie in some of the literature) is a humus-based brown-black resinous substance, formed over the centuries from plant remains (usually bryophytes) and mineral rocks. In general, it is estimated to be around 500–1,500 years old, although some samples from Central Asia have been dated at around 15,000 years. Shilajit is found in specific high altitude mountainous regions, notably Tibet and the Himalayas – although there are also sources in Russia, Afghanistan, China, Chile and Australia. There are three types of mumie: petroleum mumie (from transformed petroleum products deep in the mountains), plant mumie (vegetation-based mumie-asil) and mumie-kiem (from long-term humification of the guano of alpine rodents, notably the Rock Vole). Shilajit for medicinal use is the result of vegetation being compressed under rocks, undergoing significant compaction under high temperature and pressure conditions.7 The resultant organic material has a mineral component and is usually collected in the warmer summer months, when it liquefies to some extent and flows out from between the rock layers (Schepetkin 2009, 2002). Shilajit is an age-old geological material that has a rather remarkable therapeutic reputation in Indian traditions (Siddha, Ayurveda and Unani medicine) as a rejuvenative, antiageing, anti-inflammatory, immune-supportive and healing remedy. It has been utilised for the treatment of innumerable conditions that range from respiratory, urinary tract and digestive disorders, to neurological, emotional and memory problems. It has also been recommended for leprosy, anaemia, malabsorption, gout, injuries and numerous bone diseases (arthritis, osteoarthritis, osteochondrosis, fracture), diabetes, kidney and gall bladder stones, gastrointestinal dysfunction (gastritis, colitis, diarrhoea, dysentery), menstrual disorders, inflammatory skin problems (eczema), cardiovascular dysfunction (including haemorrhoids, heart disease, dropsy

and hypertension), tumorous growths, and as an antidote for snake bites and scorpion stings. Humic substances (60–80%) predominate in shilajit, with a fairly high level of fulvic acid (as well as humins and humic acid) – although diverse other components contribute to its value.8 Thus the pharmacological basis of Shilajit’s activity is likely to be due to a complex interaction of these substances, rather than a single component. Even so fulvic acid, which appears to make important contribution to its activity, has been utilised as an antiarthritic, antidiarrhoeal, antimicrobial, anti-inflammatory, cognition-protective, antioxidant and antidiabetic agent (Carrasco-Gallardo 2012; Cornejo 2011; Wilson 2011; Schepetkin 2009, 2002; Agarwal 2007). However, the fulvic acid component can vary in products from different locations: India (21.4%, Kumoan region), Nepal (15.4%), Pakistan (15.5%) and Russia (19%) (Agarwal 2007). Studies have confirmed that shilajit has a multitude of pharmacological properties. In most places (notably Russia, Nepal and India) where it is used in traditional medicine, it has been a highly regarded restorative tonic, valued by athletes, the military forces and the aged, as well as acquiring something of a reputation as a virility tonic. Recent recommendations include its use to promote healing following surgery in chronic suppurative otitis media, to stimulate bone regeneration following spinal operations and fracture treatments, and following tonsillectomy – as well as being recommended as a highly effective treatment for thermal burns and to promote recovery in pulmonary tuberculosis patients (Schepetkin 2002). 7 Indian references also mention a mineral-based shilajit classification based on copper (blue), gold (red), silver (white) and iron (brownish black). The latter, sourced from the Himalayas, is the most common and is regarded as being the most effective for medicinal use (Agarwal 2007). 8 These components include fatty acids, resins and waxy materials, latex, gums, albumins, triterpenes, sterols, aromatic carbolic acids, benzoic acid, fatty acids, hippuric acid, benzocoumarins, polysaccharides, polyphenols (e.g. ellagic acid) and phenolic lipids. The mineral components can be equally diverse, although concern has been raised regarding heavy metal contaminants such as lead, mercury or arsenic (see Carrasco-Gallardo 2012; Wilson 2011; Agarwal 2007).

A DESIRE FOR DIRT?

Research interest has focused on its antiarthritic, immunomodulatory and antioxidant activity, anxiety relief (anxiolytic, anti-stress), neuroprotective and memory enhancement activity – as well as radioprotective, vascular healing, antidiabetic, anti-ulcer, anti-allergic, anti-inflammatory, cholesterol-lowering, analgesic and antifungal properties. Shilajit also shows good potential for enhancing the activity of other drugs (synergistic effects) and can mediate the effects of altitude sickness. Recent studies have taken a particular interest in its use for memory disorders (including Alzheimer’s disease), neurological dysfunction (Parkinson’s disease, neuritis) and immune disorders such as AIDS – although clinical reports have indicated that its use is not applicable in multiple sclerosis (Carrasco-Gallardo 2012; Wilson 2011; Meena 2010; Schepetkin 2009; Agarwal 2007; Sharma 2003; Goel 1990). Investigations have established that dibenzo-ɑ-pyrones are shilajit components with powerful antioxidant, tissue-protective effects, that can penetrate the blood–brain barrier. These compounds are of interest because they can inhibit acetylcholinesterase, preventing the breakdown of the neurotransmitter acetylcholine – low levels of which are associated with poor memory and concentration problems (Schepetkin 2002).

Dirt in the Diet?

Earth can have some unusual avenues of entering into the diet. Often it appears as an incidental additive, usually from inadequate washing of vegetables – while experiments in ‘eating dirt’ appear to be a part of childhood learning experience, along with making ‘mud pies’. In many times and places in communities the world over, earth has been eaten out of hunger and desperation by the disadvantaged and famine-ravished, forced to resort to desperate dietary measures. In recent times the poor in Haiti have made ‘cakes’ of yellow dirt with butter, vegetable shortening and salt. Even rice was too expensive to be part of the staple diet (Associated Press 2008).

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Reproduced courtesy of Keep Calm-o-matic, www. keepcalm-o-matic.co.uk.

Deliberate dirt eating is called geophagy, which the medical profession has generally considered to be aberrant behaviour – an attitude, however, that does not allow for the cultural importance of ‘dirt in the diet’. Despite the perceived eccentricity of the practice, eating soil or clay has been observed in numerous cultures throughout the world, sometimes even forming a routine dietary component. Its use for deliberate geophagic purposes seems to have even formed an integral part of man’s relationship with the environment. Attesting to this is the fact that imported white clay was found next to the remains of Homo habilis at Kalambo Falls, Zambia. This suggested that the clay, which had to be imported, was a deliberate acquisition in prehistoric times (2.5 million years ago). Interestingly, the type of clay is the same that is utilised (eaten) today (Carretero 2002). Henry Burkill (1935) provided the following interesting overview: The custom of eating earth occurs in many parts of the world; those who chiefly adopt the habit, it was once said, are pregnant women, but this is now contested; the earth to which the eaters resort must not be gritty; otherwise any earth will do. But as the least gritty earths are fine clays, it is these which are used. Sometimes the earth is eaten in the condition in which it is found: sometimes

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it is partially baked; and sometimes it is thoroughly baked in the form of biscuits. There is never any reason for thinking that it serves as a nutriment, and there probably never is any useful chemical action between it and the digestive fluids; but it seems to relieve a feeling of emptiness in the stomach. The habit tends to become fixed.

Eating clay has been commonly practised by many African and Asian tribes. In some areas, the habit has even been considered to have useful poison antidote effects.

Salak, Salacca or Zalacca (Salacca zalacca) is an Indonesian palm tree, the sweet fruit of which (commonly known as Snake fruit) was mixed with clay, presumably to enhance its antidotal properties: ‘Earth is regarded as an antidote for poisons … the Semang believing it an antidote even for Antiaris: any earth will do, but Zalacca fruit is mixed with it … Kelantan Malays have faith in a mouthful of dry earth eaten immediately on receipt of the injury’ (Burkill 1935). Interestingly, Zalacca fruit peel (which is a waste product, left over from its culinary use) can adsorb copper ions, with potential for use as a detoxicant for industrial waste (Sirilamduan 2011). (Image courtesy Wikimedia Commons CC-by-SA 3.0 Unported)

  Animal Geophagy

Zalacca edulis (Salacca zalacca) from Berthe Hoola van Nooten, Fleurs, Fruits et Feuillages Choisis de l’Ile de Java, 1863–64. Pieter Depannemaeker (lithographer), Lederberg, Ghent.

Many animals eat earth and are quite selective about the type of soil they consume. Birds and chimpanzees have been the most common subjects for study. In Borneo Red-leaf Monkeys (Presbytis rubicunda), and in Tanzania Chimpanzees (Pan troglodytes), are known to partake of termite mounds as part of their diet – while in Peru, Moustached Tamarins (Saguinus mystax) utilise the mounds of leaf-cutting ants. These resources would contain diverse minerals, notably iron and potassium, as well as some magnesium, phosphorus and calcium. There are other sites, known as ‘licks’, that are salt-rich, providing a source of sodium that is not readily available elsewhere. Plants are often a poor dietary sodium resource, so good alternatives are readily exploited. The African Buffalo (Syncerus caffer caffer) and the Mountain Gorilla (Gorilla beringei beringei) seem to have a preference for iron-enriched clay resources.   The fact that soil may act as a detoxicant for

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The Malays believed that tigers and elephants ate earth for its medicinal qualities. Indeed, the practice could become so well established in elephants as to be considered an aberration. Sir George Maxwell’s translation of Mantra Gajah included the following antidote: ‘it is directed that to break elephants from the habit, baked earth worms should be mixed with black earth and this given to them’. (Image courtesy Chris Crosland & Jenny Shepherd) Vervet Monkey (Chlorocebus pygerythrus), in the Krugersdorp Safari Reserve, South Africa.

harmful plant chemicals could well be a motivating factor behind its use by numerous animals – notably apes, lemurs, monkeys and various birds. In addition, the antacid and antidiarrhoeal properties of kaolin-based clays would be familiar to some species (Abrahams 2005).   Doubtless, similar to humans, different animals in different regions have their own favourite supplies. Certainly, African and Asian elephants have a preference for some clay sites over others (Limpitlaw 2010). A Sri Lankan study found that soils eaten by elephants were richer in kaolinite and illite in comparison to non-geophagic soils, which contained higher amounts of smectite. It was suggested that the elephants ate the soil, not as a mineral supplement, but as a detoxicant to deal with unpalatable dietary components (Chandrajith 2009).

Early last century Walter Roth observed that in Australia: White clay, a kaolin (hydrous silicate of alumina), is eaten, both at the Bloomfield and at Cooktown in northern Queensland. In the former district, it is generally … dug out from the veins in the cliffs or in the banks of the creeks, and then carefully pounded and sifted, so as to render it quite smooth and free from grit. It is next placed in a bark trough, and, by the addition of water, worked into a stiff paste. This paste is now made into a cake … and placed in the sun for from six to eight days, when it is eventually wrapped up in leaves, buried in the ashes, and a hot fire made over it. When cool, it is ready for use and considered a delicacy. Clay from the ant-hills (outside covering) was also part of the diet at Bloomfield: ‘used to “fill up” with’ when no other edible substance is available. The women and piccaninnies seem always able to eat of this, even after a meal of things more nourishing: it requires no preparation, and is known as kappi (Roth 1901).

Similar uses of clay were recorded from the Northern Territory (Barr 1988; Bateson & Lebroy 1978). On

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Groote Eylandt a white riverine-sourced clay was sometimes eaten by Aboriginal women if they were hungry (it was said to taste like fish), although it was not eaten by the men. The clay was also considered to be a useful anti-diarrhoeal agent and could be taken by pregnant women to ‘make their stomach cool’ – albeit said to cause constipation if too much was eaten (Levitt 1981). The reference to the constipating effect is of interest. The absorption capacity of the intestine can be compromised by excessive clay ingestion, resulting in abdominal discomfort. X-ray studies have clearly shown that clay balls can form in the intestine. Their presence can be highly problematic if they result in intestinal obstruction – a very painful and distressing situation. In severe instances, perforation of the bowel has occurred (Abrahams 2002; Ginaldi 1988; Bateson & Lebroy 1978).

  Strange Desires

The term ‘pica’ has been used to describe the unusual cravings of pregnant women who eat dirt – a somewhat off-key habit that has generally been tolerated, and regarded as a temporary aberration. However, in medical circles pica can refer to any abnormal craving, such as eating paper, rubber, chalk and numerous other odd items – some of which can be quite incompatible with dietary requirements. Medical opinion has, overall, considered dirt-eating to be quite abnormal – and it has sometimes been equated with serious mental instability. This opinion is, rather dramatically, reflected in the writings of Avicenna (around AD 1000) who even called for the control of it ‘in boys by use of the whip, in older patients by restraints, prison and medical exhibits, while incorrigible ones are abandoned to the grave’ (cited in Halsted 1968). A serious misdemeanour indeed. While the habit has often been associated with mental disorders, whether geophagy itself actually falls into that category continues to be a matter for debate. Geophagy has endured over the ages. Many cultures have utilised earth and clay in the diet and may well have derived various mineral supplements from the practice.

This display in the Glore Psychiatric Museum, Saint Joseph, Missouri, shows the stomach contents of a former inmate – demonstrating the bizarre nature of some psychiatric problems. The patient swallowed over 1,446 items, which included 453 nails and 42 screws – as well as safety pins, spoon tops, salt and pepper shaker tops. She did not survive surgery to remove the offending objects.

Mineral Matters

There have been numerous studies that show interesting variations in the mineral content of edible forms of clay.9 These investigations provide an indication of the differences in clay samples sourced from different geological regions – and there is always an exception to general expectations. For instance, while most clays are salt-free, the use of ‘salty clay’ has been recorded in South America and salt-enriched earth in India (Abrahams & Parsons 1996): Africa, Zanzibar (Pemba Island): levels were •  insignificant for phosphorus (0.00–0.09%), sodium (0.00–0.76%), manganese (0.00–0.04%), and fairly low for calcium 0.04–2.97%), magnesium (0.13–1.16%) and potassium (0.06–2.12%); iron levels were higher (0.46–5.74%). Zinc could also be present (4–44 ppm) (Young 2010a). • Africa: clays sourced from Gabon, Kenya, Nigeria, Togo, Zambia and Zaire showed substantial variability and were generally low in phosphorus (175–349 mcg/g). The difference in other mineral levels could be significant: calcium (143–4145 mcg/g), magnesium (603–1628 mcg/gm), zinc 9 The overall lowest–highest mineral levels are noted for these studies. However, greater detail regarding individual clay types and more complete mineral analysis is available in the original papers. (See also Abrahams 2005; Tateo & Summa 2007.)

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(12–185 mcg/g), manganese (155–3408 mcg/g). Some samples had a particularly high iron content (11.6–60.0 mg/g[sic]) (Johns & Duquette 1991). • USA: Californian clay minerals were found to be similar to some African samples: calcium (4217 mcg/g), phosphorus (393 mcg/g), magnesium (3980 mcg/g) manganese (3980 mcg/g), as well as being high in iron (39.3 mg/g[sic]) (Johns & Duquette 1991) •  Sardinia: low phosphorus (131–436 mcg/g) and manganese (38–86 mcg/g), with higher levels of calcium (3788–5718 mcg/g), magnesium (5608– 8924 mcg/g) and zinc (57–110 mcg/g). Iron values (34.1–51.6 mg/g) were high (Johns & Duguette 1991). Certainly this indicates that there is substantial potential for differences in the effects associated with the use of clay in the diet. Studies from Australia have shown a similar amount of variability in clay mineralogy, including clay sourced from termite mounds, which is quite a popular resource in many countries where geophagy is practised. (Below) Edible clay is often found around riverine sites – as are coloured clay ‘stones’, which are of a soft consistency. In northern Queensland, edible clay deposits have been sourced from the Bloomfield River (shown here), Saltwater River (near Pollock’s Crossing) and Barrats Creek (gumbura clay) – as well as the Daintree River, where a soft stone, ‘like a talc’, was found in many colour forms: purple, pink, yellow, white, brown and red. These different clays contain a variety of trace elements (Rowland 2002).

Ochre rocks are often found in streams. Daintree National Park

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Table 6.1 White Clay and Termitaria Samples from the Northern Territory

Investigations evaluating the mineral content of clay have unearthed some interesting support for its use. Samples were shown to contain the following concentration of calcium, magnesium, iron, potassium, and sodium (mg/100 g): Clay type

Ca

Mg

Fe

K

Na

Termitaria: soil 10 cm inside mound (Barr 1993)

10–11 mg

27–38 mg

780–4341 mg

71–95 mg

3.1–3.2 mg

Termitaria: mound casing (Barr 1993)

104–166 mg

113–156 mg

1327–2217 mg

139–166 mg

4.8–5.8 mg

393 mg

15 mg

572 mg

3798 mg

0.12–0.14%

1.0%

0.38%

0.09%

White kaolin clay from Yirrkala 119 mg (Barr 1993) Groote Eylandt: silicate clay (Levitt 1981)*

aluminium —

* Analysis by Groote Mining Company (mineral oxide %): silica (SiO 66.6%) and aluminium (AlO 24.5%), additional minerals present in small amounts included strontium (SrO 0.03%), barium (BaO 0.14%), titanium (TiO 0.63%) and phosphorus (0.34%) (Levitt 1981).

Table 6.2 Summary of Australian Clay Resources Utilised by Aboriginal People See Rowland (2002) for a more detailed discussion. Northern Territory: Groote Eylandt Northern Territory: Groote Eylandt Northern Territory

Red or yellow clay (malarra) Termite mound clay (ebinga) White clay (duingira)

Clay: eaten for mineral deficiencies (Levitt 1981)

White clay (Benamanrkagunara, White Clay Dreaming)

Clay: highly prized and used for gastrointestinal disorders and diarrhoea (Eastwell 1979; ) White clay (kaolin): baked in fire, like a damper, then made into pellets or powder (1 teaspoon) mixed with water and taken for diarrhoea (Barr 1988). White clay: ‘used as a medicine to cure stomach aches and diarrhoea. And to “settle the stomach” when it is upset … also taken to “line the stomach” before eating yams or fish which may be poisonous’. Clay eaten to allay hunger and for hookworm infestation (Bateson & Lebroy 1978) Clay from termite mound (Arnhem Land): gastrointestinal disorders (Eastwell 1979). Termitaria: gastrointestinal problems; eaten by pregnant women (Foti 1994; Barr 1993, 1988). Ant-hill earth extract (boiled in water) used for stomach aches and diarrhoea (Bateson & Lebroy 1978). Clay: eaten, drunk in solution, rubbed over body: cure for internal pain, headache, joint pain, eye complaints, snake-bite wounds; increases flow of breast milk (white clay) (Memmott 1979). Clay: kneaded into balls, rolled in banana leaves and roasted: eaten by pregnant women to ensure birth of a fair-skinned child. Children ate clay to make them ‘stronger, braver, sturdier’ (Alfred Cort Haddon, cited in Rowland 2002). Riverine clay: sieved to remove all coarse particles. Refined clay put in trough, mixed with water to make a dough. This was kneaded to make long flat cakes that were sundried (6–8 days). Cakes then roasted in earth oven: wrapped in leaves, buried in ashes and fire lit above them. When cooled they were considered a great delicacy (Anell & Langercrantz 1958). Large clay or mud pills: 1–2 taken for diarrhoea (Roth 1897).

Northern Territory

Termite mound (anthill earth; termitaria)

Mornington Island

White clay

Torres Straits, Murray (Mer) Clay: ‘greasy chocolate-like Island earth’

Queensland (northern): Bloomfield

White kaolin clay

Queensland: northwest and central regions

Clay

Clay: anti-diarrhoeal (Levitt 1981)

A DESIRE FOR DIRT? Queensland: Cape York

White clay

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Clay: white (kaolin) clay from the beach mixed with water, washed and strained, used as a treatment for coughing or tuberculosis; clay also eaten as an anti-diarrhoeal agent (Isaacs 1987). Fire-roasted clay mixed with water and a teaspoon taken as an antidiarrhoeal agent (Barr 1993).

Queensland (northern): Clay Evelyn Tableland Queensland: Taroom Soft white stone (copi)

Clay: eaten as an abortive and contraceptive (Mjoberg 1918).

Western Australia

Red clay (wilgi) White pipeclay

Clay heated and mixed with emu oil, applied on a dressing (paperbark, gumleaf or wad of possum fur) to wounds. Clay also applied to sore eyes (Hammond 1980).

Western Australia

Broolga (red earth)

Clay eaten for stomach trouble (White 1985).

Clay heated and made into a fine powder (resembling cornflour), mixed with water: used for a variety of ailments (L’Oste-Brown & Godwin 1995).

In Australia red-brown termite mounds have been commonly used as a supplement by Aboriginal women during pregnancy and following delivery. The earth was regarded as having tonic attributes – as well as being useful for easing abdominal pain and to promote lactation. It was taken by young girls to ease period pain, and widely used as an absorbent antidiarrhoeal remedy (Barr 1993, 1988). Dulcie Levitt (1981) comments: ‘clay from termite mounds was usually eaten by women who had been inland for some time, living on roots and wild honey. It was probably eaten to cure mineral deficiency. Clay processed by animals was considered to be safer than other kinds. The clay was crumbled in the hand to a powder, which was dropped into the mouth. The clay termite tunnels in logs were also eaten’.

Mangrove worms (Teredo novalis). Coastal Aboriginal tribes can utilise a substantial range of marine resources as food. Among them are Mangrove worms, which may provide another incidental source of dirt in the diet. Bateson and Lebroy (1978) commented: ‘Another source of ingested clay may be the mangrove worms eaten by Tiwi people. These worms inhabit the mud around the roots of mangrove trees. These worms are swallowed whole after their intestinal contents have been expressed, but it is highly likely that some mud will remain and so be present in the alimentary tract of the consumers.’ Not only are these worms harvested wild by Australian Aboriginal people, but in parts of Southeast Asia they are considered a delicacy. (Upper image courtesy Coleen P Sucgang, Poseidon Sciences; lower image courtesy Rita Albert, www.flickr.com/photos/rietje/4631747412)

Two different types of clay have been used to build these termite mounds, which have been decorated with images of the kangaroo and emu (‘bush graffiti’). Clays that have a reddish colour tend towards a higher iron content. (The ecological role of termite mounds is discussed in Chapter 7.)

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In cases of dietary deficiency, some minerals can take on greater importance than would be normally expected. Certainly, magnesium is known to have significant antispasmodic properties – although the question of mineral bioavailability is an important issue that does not appear to have been reliably solved with regard to geophagic habits. In general, the levels of most minerals found in termite nest soils (red-brown, yellow, grey earths) are not very high, although iron and sodium can be an exception. Some types are even considered to enable a measure of electrolyte replacement (Barr 1993) – although this would depend on the mineral composition and exchangeable ion qualities of the earth ingested. Mineral levels were consistently higher in the covering of the mound than from soil within the mound, which means that Aboriginal people’s selection of pieces of the outer casing (from newly built sections) was a wise choice. The earth was either crushed and eaten on its own, or larger pieces (palm-sized) were ground into a powder and mixed with around a litre of liquid (water, milk, tea) to make a fine suspension. Sometimes the casing was burnt before grinding, at other times a particular mound could be preferred, such as those found at the base of Eucalyptus tectifica. In some places honey ants (Melophorus spp.) were even added to the mixture (Barr 1993, 1988). The use of termite nests and termites for food was mentioned by the German anthropologist Berthold Laufer (1930):

White-ants’ nests constructed of soft, fine earth, generally of a reddish black color, are consumed in India in the same manner as in Africa. Coolies of Assam are disposed toward white-ant soil taken from the center of the nest, white ants themselves being included as a delicacy … Among the mountain tribes of Travancore the men, not the women, eat this earth with the ants inside the cells, sometimes adding honey to it. It is taken, not in small medicinal doses, but in rather large quantities. No evil effects have been noticed to follow its use ... Steatite or soapstone ground to powder and mixed with flour has served in India as a regular famine food, in the same manner as in China.

In some Indian traditions termites (Odontotermes formosanus) were eaten to enhance lactation and studies have suggested that they are a good proteinrich dietary resource (560 calories/100 g), superior to steak (322 calories/100 g). They contain a high fat component for an insect (around 600–760 kcal/100 g) – as well as carbohydrate, a range of essential amino acids and, depending on the species, good amounts of various minerals (Solavan 2006).

  Termites and Spinifex

Spinifex triodia, Finke Gorge National Park. (Courtesy Craig Nieminski, flickr)

Mud wasp at nest. Occasionally mud wasp nests have been utilised as a source of geophagic clay, such as those of the mud-daubing wasps (genus Synagris) from Sierra Leone, albeit not a common practice (Abrahams 2005).

Termite mounds found near clumps of Spinifex grass (Triodia pungens) incorporate this resinyielding plant into the mound, which makes an effective aromatic repellent when burnt – and explains its use as a mosquito repellent (Lindsay 2001). The smoke is thought to have healing properties for sick babies – and ‘smoking’ (or fumigation) is a traditional treatment for diverse forms of illness (Barr 1988). This is an interesting concept, about which Professor John Pearn (2005) comments:

A DESIRE FOR DIRT? The smoking of infants has deep ritual significance and is still widely used. Aboriginal peoples in many communities today believe that the smoking of infants has important pro-active protective medical overtones. There is a fundamental and deeply held implication also that the smoking rituals will have long-term effects and make babies strong and placid. The smoking of infants is undertaken by mothers and grandmothers, often as an unhurried and enjoyable practical ceremony conducted within the fellowship of a small women’s kinship group. A fire-pit is dug, a fire lit and hot coals prepared. Pieces of resinous termite mound are added to the hot coals. The resinous material which is used for infant-smoking is specific for different communities. In some communities ofthe Ngarinyman and in those of the Warlpiri, termite mounds are found particularly amongst clumps of the Spinifex Grass, Triodia pungens. Leafy green branches are then placed on top of the glowing coals in the fire-pit. When there is a continuous flow of smoke, and in the absence of any flame, the baby is held lovingly above the leaves, and is invested by the smoke. The smoking continues until the fire-base cools.   In the smoking of babies, leaves from any one of several species are used by communities in Central Australia. These include: Acacia aneura, Acacia lysiphloia, Eulalia aurea, Exocarpos latifolius, and Dodonaea viscosa. It is interesting that these five species contain little or no essential oils, but generally contain triterpenes and higher than average concentrations of tannins (6 per cent of dry weight in the case of Exocarpos) and saponins.

In addition, termite mound pieces were added to meals cooked in an earth oven to impart a distinctive ‘smoky’ flavour to meats such as turtle, fish or kangaroo. Furthermore, termite eggs and larvae are considered to possess useful healing effects, and have been used as a liniment (Low 1991; Barr 1988). This could possibly be due to the fact that termites are oil-rich insects – which have been used in Africa and some parts of Asia as a dietary resource. In the Northern Territory a post-natal remedy was prepared from a clump of Spinifex, crushed with a little dark-coloured termite mound and warmed on a bed of coals to extract a soft dark resin. The mix is crushed, sometimes a small amount of water added,

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and the resultant liquid used by a mother after childbirth. Small sips could be given to the baby to promote good health and ensure its strength. The grass decoction could also be recommended as a body wash for treating colds and influenza. Another Spinifex, Triodia microstachya, has been utilised as a decongestant decoction for treating influenza, coughs and respiratory congestion. It is considered to be a powerful medicine that has been widely used in preference to ‘clinic medicine’ (conventional drugs). It is also useful for skin infections and scabies (Wightman 1994, 1991; Barr 1993; Smith 1993).

Spinifex hummock grasslands at Karijini National Park, Western Australia. The green hummocks are Triodia pungens (Soft Spinifex); the blue-grey hummocks are Triodia basedowii (Hard Spinifex or Lobed Spinifex). The trees in the background are Eucalyptus and Acacia species. (Image PW Hattersley, in L Watson & MJ Dallwitz (eds), The Grass Genera of the World, 1992, CAB International, Wallingford, UK)

The Downside of Clay Ingestion

The detoxicant properties of clay can benefit digestion by binding with toxic substances present in the bowel, thereby having a cleansing effect. This is due to a very small particle size ( 4)-β-Dglucopyranoside obtained as a new anticancer agent from Dioscorea futschauensis induces apoptosis on human colon carcinoma HCT-15 cells via mitochondriacontrolled apoptotic pathway. J Asian Nat Prod Res. Vol. 6/2, pp. 115–25.

Song MY et al. 2009. Antiobesity activity of aqueous extracts of Rhizoma Dioscoreae [sic] Tokoronis on high-fat diet-induced obesity in mice. J Med Food. Vol. 12/2, pp. 304–09.

Wang T et al. 2010a. Antihyperlipidemic effect of protodioscin, an active ingredient isolated from the rhizomes of Dioscorea nipponica. Planta Med. Vol. 76/15, pp. 1642–46.

Stuart Rev. GA. 1911. Chinese Materia Medica: Vegetable Kingdom. Southern Materials Center Inc., Republic of China. [1987 reprint.]

Wang T et al. 2012. Trillin, a steroidal saponin isolated from the rhizomes of Dioscorea nipponica, exerts protective effects against hyperlipidemia and oxidative stress. J Ethnopharmacol. Vol. 139/1, pp. 214–20.

Su PF et al. 2011. Dioscorea phytocompounds enhance murine splenocyte proliferation ex vivo and improve regeneration of bone marrow cells in vivo. J Evid Based Complementary Altern Med. 2011:731308. Sumioka I et al. 2006. Lipid-lowering effect of monascus garlic fermented extract (MGFE) in hyperlipidemic subjects. Hiroshima J Med Sci. Vol. 55/2, pp. 59–64.

Wang W, Lu DP. 2005. An in vitro study of cytotoxic and antineoplastic effect of Solanum nigrum L. extract on U266. Beijing Da Xue Xue Bao. Vol. 37/3, pp. 240–44. [Chinese]

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INDEX α α-aescin 125 α-bisabolol 67–70 α-cadinol 82 α-calacorene 82 α-cedrene 328 α-chaconine 455 α-copaene  97, 104 α-cubebene 70 α-humulene  101, 142, 462 α-linolenic acid  34, 119 α-muurolene 82 α-phellandrene  177, 316, 462 α-pinene  33, 43, 56, 95, 101, 104, 177, 300, 315, 316 α-solamargine 455 α-solanine  455, 465 α-solasonine 455 α-terpineol  44, 101, 320 α-terpinolene  95, 104, 462 α-terpinyl acetate 95 α-terthienyl  85, 86, 87 α-thujene 104 α-tocopherol  31, 119, 140 α-tomatine 455 α-zingiberene 104 β β-aescin  125, 128 β-bisabolene 44 β-bourbonene 104 β-carotene  31, 32, 33, 117, 119, 142 β-caryophyllene  97, 104, 142, 319, 462 β-chaconine 485 β-cryptoxanthin 33 β-eudesmol  313, 318 β-farnesene 104 β-ionine 82 β-lactamase 321 β-phellandrene  44, 104 β-pinene  33, 95, 104, 315, 316, 462 β-selinene 101 β-sesquiphellandrene 44 β-sitosterol  150, 171, 435, 445, 477, 479, 481 β-soladulcine 455 γ γ-cadinene 82 γ-elemene  88, 315, 318 γ-muurolene  82, 319 γ-terpinene  43, 101, 104, 316 δ δ-cadinene 82 κ κ-strophanthoside 485 ρ ρ-amino salicylic acid  174

ρ-cymene  43, 101, 104, 462 ρ-cymol  142, 149 ρ-methoxyphenylacetone 42 A Abrus precatorius 184 Acacia  149, 391 ancistrocarpum 256 aneura  269, 392, 407, 426 aulacocarpa 133 auriculiformis 324 bivenosa 324 complanta 133 cuthbertsonii 377 hakeoides  373, 392 kempeana 324 leiophylla 308 ligulata  182, 324, 392 nilotica 83 pendula 299 salicina  375, 391 spp. 394 stenophylla 392 Acanthamoeba castellanii 97 polyphaga 97 Acanthocheilonema vitae 282 Acanthospermum australe 97 acetaminophen 54 acetyl salicylic acid 54 acetylcholine  261, 361, 364, 365, 366, 368, 396, 469 acetylcholinesterase  102, 103, 261, 363, 366 acetyleugenol 43 Achillea millefolium   158 Achyranthes arborescens 184 aspera 184 margaretarum 184 acid acetyl salicylic 54 asiatic 142 benzoic 20 betulinic 150 brahmic 143 caffeic  57, 108 carnosic 144 centellic 143 chaulmoogric 164 chicoric 73 chlorogenic  73, 108, 356, 454 dicaffeoyltartaric 73 gallic 104 hydnocarpic 165 isobrahmic 143 kaurenoic  54, 56, 57, 66

linolic 164 madasiatic 142 madecassic  142, 143 nicotinic 415 oleanolic  56, 80, 338 polygalacic 50 rosmarinic  102, 104, 144, 145 taraxinic 76 terminolic 143 thankunic 143 ursolic  144, 398 Ackama muelleri 393 Acmella brasiliensis 54–57 calva  56, 57 grandiflora  52, 61 grandiflora var. brachyglossa 52 grandiflora var. discoidea 52 grandiflora var. grandiflora 52 oleracea  51, 52, 56 paniculata 52 uliginosa 52 Acmena smithii 91 Aconite  10, 47, 212 Aconitum napellus  10, 212 Acorus calamus  151, 152 Actinomadura madurae 200 Actinomyces antibioticus 200 actinomycin  200, 205 Adansonia gregorii 133 adonidin 25 adonilide 26 adonin 26 Adonis  24, 25, 26 Amur 26 amurensis 26 microcarpa  24, 25 Summer 25 vernalis  25, 26 adonitoxin 25 adrenaline  12, 325 adriamycin 201 Adriana glabrata 420 Adrucil 35 Aedes aegypti 87 fluviatilis 64 Aegiceras corniculatum  182, 183 aegicerin 182 Aeromonas hydrophila 148 aescin 124–9 aesculin  73, 124, 125, 130 Aesculus hippocastanum 124–6 indica 126 affinin 57 African Marigold  84, 85

541

Agave  447, 482 amaniensis 447 americana 448 cantala 482 rigida 447 sisalana  447, 448 spp. 451 aglycone 455 Agrimonia pilosa 475 Agrobacterium tumefaciens 55 Agrostis stolonifera 330 Ailanthus altissima 184 glandulosa 184 integrifolia 184 triphysa 184 Ajuga australis 133 Alchemilla speciosa 129 aldrin 237 Aleurites moluccana 156 Allium bakeri 65 sativa 158 sativum 174 Allocasuarina littoralis 133 Allolobophora caliginosa trapezoides 288 allopurinol 130 Aloe vera  121, 481 Alpinia arctiflora 184 arundelliana 184 caerulea 184 galanga 184 hylandii 184 modesta 184 racemigera 184 Alstonia 393 actinophylla  316, 393 constricta  392, 394 scholaris 393 Alternaria alternata 103 solani 335 Amanita muscaria  123, 367 phalloides 368 Amaranthus chlorostachys 82 Amegilla cingulata 308 American Nightshade  451, 464–6, 482–4 aminoglycoside 483 Amitermes laurentis 302 meridionalis 302 Amla 151 Amorphophallus

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campanulatus 184 galbra 184 paeoniifolius 184 amphotericin 483 Amulla 294 Amur Adonis 26 Amyema quandong 133 anabasine  396, 398, 406, 407, 412, 415, 416 anagyrine 415 Ancylostoma caninum 276 duodenale  274, 276 Andrographis paniculata 64 androstenedione 434 anethole  42, 44 Anethum sowa 39 Angel’s Trumpet  354, 350, 395 Angelica sinensis  69, 475 Anise oil  20, 42 Aniseed 42 anisodamine  359, 360 anisodine  359, 360 ankaflavin  441, 443, 444 Annona cherimolia 54 glabra 54 senegalensis 54 squamosa x A. cherimolia 55 anonaine 177 Anopheles stephensi  101, 116, 149 subpictus  87, 149 anthecotulide 68 anthelminthicin 170 Anthemis arvensis  66, 67 cotula 68 nobilis  66, 68 Antheum graveolens 43 Anthocercis aromaticus 398 fasciculata 398 frondosa 398 genistoides 398 ilicifolia 398 littorea 398 viscosa  398, 399 anthocyanidin  19, 130 Anthotroche myoporoides 398 pannosa 398 walcottii  398, 399 antimony  209, 210 anymol 327 apigenin  66, 67, 69, 120, 171, 172, 179, 429 apigenin 7-glycoside 70 Apis 47 Apis mellifera 307 apoatropine  355, 358, 396, 398 Apocynum 212 Apodemus sylvaticus 281 aporphine 177 aposcopolamine  396, 398 Apple Bitter 454 Custard 55 Devil’s 477 Kangaroo  454, 456 Mountain Kangaroo 454 Winter 294 Wolf 478

Apple of Sodom 475 Applebush  96, 182 Ara chloropterus 223 Arabidopsis thaliana 469 Araucaria bidwillii 133 Areca catechu 372 Armoracia rusticana 378 armyworm, Asian  164 Arnebia euchroma 475 Arnica  47, 59, 79 Arnica montana 58 aromadendrene  300, 318, 327 arsenic  230, 231 Artemisia annua  97, 98 capillaris 129 montana 129 scoparia 129 artemisinin 97 asbestos  226, 236, 237, 476 Ascaris lumbricoides  165, 275, 279, 280 suum 280 trichuris 275 ascorbic acid  32, 33, 119, 445 asiatic acid  140, 142–4, 148, 149 6-β-hydroxy-asiatic acid  143 asiaticoside  140, 142–4, 146, 148, 149, 155 asimilobine 177 Aspalathus linearis 172 Asparagus racemosus 151 Aspergillus  55, 56, 69, 194, 199, 482 flavus  55, 56, 217, 335, 462 niger  50, 55, 56, 121, 133, 135, 148, 335 parasiticus 55 aspirin  54, 57, 130, 149, 192 Asteromyrtus shepherdii 133 symphyocarpa 133 Astragalus membranaceus 64 Astrotricha longifolia 133 Atalaya hemiglauca 306 variifolia 307 Atemoya  54, 55 Athanasia crithmifolia 328 Atropa belladonna  341, 342, 353, 355, 357, 359, 384, 394, 463 atropine  220, 227, 341, 344–6, 349, 353–60, 362, 364, 366, 368, 384–90, 394–6, 401, 415, 463, 472, 488 Attar of Roses  30, 31 aureomycin 198 Australian Buckthorn  123 Australian Corkwood 387 Australian Paralysis Tick  412 Australian Sneezewort 50 Australian Tobacco 404 Azadirachta indica  39, 164, 184 Aztec Marigold  83, 84, 87 azulene 67 B Bacillus cereus  36, 54, 132, 148, 335 dysenteriae 109 megaterium 148 subtilis  29, 55, 56, 80, 98, 103, 109, 121, 133, 148, 244, 334, 459 typhi 109 Backhousia citriodora  131, 133 Bacopa

floribunda 150 monnieri  137, 150, 152, 158, 428 procumbens 150 bacosine 150 Bacteroides vulgatus 36 Bai-ji 174 Baileyoxylon lanceolatum  166, 167 Balanops australiana 133 Bandicoot, Southern Brown  285 Banksia collina 133 Baptisia alba 415 Barbat Skullcap  474, 475 Barmah Forest virus 203 Basil  98, 179 Bastard Sandalwood oil 131 Bat Plant 446 Baylisascaris procyonis 275 Beach Sunflower  53, 56, 59, 60, 61, 156 Bean Calabar 362 Mescal 416 Ordeal 361 Soya 480 beauvericin 435 BEC 476 Bee Blue Banded  308 Cuckoo 308 Belladonna  18, 349, 383–8 belladonnine 355 Belleric Myrobalans  151 Bellis perennis  48, 49, 50 Benamanrka-gunara 266 bentonite  217, 221, 226–8, 234, 238, 240, 253, 254, 256, 271, 273, 275 benzocaine 371 benzoic acid 20 benzoin  46, 437 benztropine 359 berberine  97, 112, 171 Berberis aristata 39 Bergamot oil  105 Bergsmia javanica 167 Berrigan  316, 320 Berry, Turkey 458 Beta vulgaris 344 betalain 122 betaxanthin 122 Betel Nut  116, 372, 373, 392 betulinic acid  35, 143, 150, 171 Beyeria lechenaultii 133 bicyclogermacrene 142 Bidens bipinnata 184 pilosa 184 subalternans 184 tripartita 184 biflorin  316, 318, 319, 328 Bilberry  385, 386 Bilharzia  280, 282 Biomphalaria peregrina  54, 57 bisabolene  315, 327 bisabolol  67, 69, 70, 80 bisphenol A  123 Bitter Apple  454 Bitter Jessie 440 Bitter Yam  438, 439 Bitterbark 394 Bittersweet  189, 455, 462–4, 470, 471, 472 Black Garlic  175 Black Hellebore  486, 487

Black Lily 446 Black Nightshade  451, 455, 462–6, 468–74, 483 Black Orchid 419 Black Pepper 417 Blackbean  2, 131, 418 Blainvillea dubia 52 gayana 52 bleomycin 201 Bletilla striata 174 Blue Coleus 103 Blue Gum  149, 190 Blue Lobelia 423 Blueberry Tree  293 Boerhaavia diffusa 39 Bombyx mori 284 Bontia daphnoides 297 Boobialla Common 293 Creeping 293 Pointed 380 Southern 293 Western 294 Boophilus decoloratus 454 Borage, Indian  100 Bordetella bronchiseptica 334 pertussis 281 borneol  43, 44, 70, 95, 316, 320 bornyl acetate  70, 320 Boronia 32 Boronia megastigma 32 spp. 133 Boswellia carterii 75 Botrytis cinerea 54,135 Bottlebrush 182 Bougainvillea spectabilis 129 Brachychiton acerifolius 133 Brahmi  137, 150, 151, 158, 428 Brahmia indica 150 Brahmic acid  143 brahminoside 143 brahmoside 143 Brazilian Cress 53 Brazilian Nightshade 451 Brazilian Pennywort  139 Brazilian Potato Tree 451 Brown Plum  370, 371 Brucea javanica  172, 184 bruceantin 172 bruceine 172 bruceoside 184 Brugia malayi 280 Brugmansia arborea 395 knightii 395 sanguinea  354, 355, 356 suaveolens 395 x candida 395 Buckinghamia celsissima 133 Buddleia cordata 179 Buddleja davidii 179 globosa 326 Bufo marinus 341 bufotenin 341 Bulbine frutescens  140, 141 Bulrush 220 Bunya Nut  133 Burn Jelly Plant  141 Bursaria calciocola 124

INDEX incana 123 longisepala 124 occidentalis  123, 124 reevesii 124 spinosa  123, 125 tenuifolia. 123 Buruli ulcer  175, 202, 203, 286 Buscopan 401 Bush Cattle 420 Coca 370 Crimson Fuchsia  315 Desert Fuchsia  315 Drummond’s Poverty  324 Ellangowan Poison  294, 311 Flannel 452 Harlequin Fuchsia  314, 321 Kerosene 318 Narrow-leaf Fuchsia  313 Pituri 380 Purple Fuchsia  315 Red Poverty  314 Rock Fuchsia  315 Smelly 88 Spotted Fuchsia  317 Spotted Poverty  323 Tar 297 Turkey 315 Turpentine  314, 318, 321 Warty Fuchsia  311 C Cabbage Rose 38 Cacalia ainsliaeflora 329 decomposita 329 delphinifolia 329 pilgeriana 329 cacalohastin 330 cacalol  325, 330 cacalone 329 Cachexia Africana  273 cactinomycin 200 cadinane 327 cadinene  70, 82 cadmium 233 Caesalpinia bonduc 185 crista 185 digyna 185 erythrocarpa 185 hymenocarpa 185 major 185 nitens 185 pulcherrima 185 robusta 185 sappan 185 subtropica 185 traceyi 185 caffeic acid  57, 70, 104, 108, 119, 144 Calabar Bean 362 calamenene 327 Calamphoreus inflatus 297 calcalone 330 Caldcluvia paniculosa  393, 394 Calendula alata 82 arvensis  67, 81 officinalis  77–9, 81, 141 Calendula oil  80 calenduloside B 81 Callistemon citrinus  133, 182

salignus 133 Caloncoba echinata 163 Calotropis gigantea 170 Camel Poison 378 Camellia sinensis 58 campesterol  435, 445, 479, 480 camphene 44 camphor  20, 43, 178, 185 camphora 47 camphorene 327 Campylobacter jejuni 81 Candida albicans  35, 55, 56, 81, 103, 113, 121, 133, 148, 172, 205, 298, 330, 334, 335, 436, 459, 462, 482 dubliniensis 81 glabrata 81 guilliermondii 81 krusei  81, 139 maltosa 334 parapsilosus 81 tropicalis  56, 81 Cane Toad  341 Canine hookworm 276 Canine roundworm  276 Canine whipworm  276 Canna indica 83 cannabichromene 192 cannabidiol  191, 192 cannabidiolic acid  191 cannabigerol  191, 192 cannabigerolic acid  191 cannabinol 192 Cannabis sativa  185, 191, 347 Canscora decussata 185 diffusa 185 cantalasaponin-3 482 Canthium oleifolium 91 Cape York Lily  159 Capparis spinosa 158 Capraria biflora  319, 320 lanceolata 319 Capsella bursa-pastoris 185 capsicastrine 477 capsimine 477 Caraway 43 Caraway oil 43 carbon-tetrachloride 57 Cardamomum  39, 43 Cardinal Flower  425, 429 cardiogenin 37 Carduus marianus 158 Carica papaya 185 Carissa lanceolata 133 carnosic acid  144 carnosol 144 carotene  40, 142 carpesterol  459, 477, 482 Carpotroche brasiliensis  163, 165, 173 Carum carvi 43 carvacrol  101, 104 carvacrol acetate  104 carveol 43 carvone  43, 45 caryophyllene  43, 88, 101, 104, 142, 149, 462 caryophyllene oxide  104, 462 Casearia grayi 133 multinervosa 133

sp. (Mission Beach)  133 Cassia occidentalis  53, 158 Cassia bark 43 Cassowary 168 Castanospermum australe  2, 131, 133, 418 casuarictin 36 Casuarina cristata 185 cunninghamiana 185 equisetifolia 185 glauca 185 obesa 185 pauper 185 catalpol 317 catechin  128, 142, 445 Catha edulis 373 Catharanthus roseus  10, 185 Cattle Bush 420 Cauliflower, Pink  95 Caulinia nigricans 202 Cedrus deodara 39 Celery seed oil  105 Centella asiatica  137, 138, 140, 141, 144, 147–50, 152, 155, 156, 169, 428 cordifolia 144 centellasaponins 143 centellic acid  143 centelloside 143 Centipeda borealis 105 crateriformis 106 cunninghamii  50, 105, 108, 133 minima  105, 108, 109 minima subsp. macrocephala 105 minima subsp. minima 105 nidiformis 106 orbicularis 105 pleiocephala 106 racemosa 106 thespidioides  105, 106 Ceratanthus longicornis 133 cerubidin 201 Cestrum diurnum  488, 489 dumetorum 489 elegans  487, 488 fasciculatum 487 Green  488, 489 laevigatum 489 nocturnum 488 Orange 488 parqui  488, 489 Red 487 cevadine 485 chaconine  455, 460, 481 chacotriose 460 Chagas disease  57 Chamaemelum nobile  66, 67 chamazulene  67, 69, 70 Chamelaucium uncinatum  94, 95 Chamomile Corn  66, 67, 180 German  66, 67, 81 Lawn 68 Roman  66–68, 81 True 66 Yellow 67 Chamomilla recutita 66 chard  86, 344 Chatham Island Pratia 430 Chaulmoogra  161, 164

543 chaulmoogra oil  161–4, 166, 169, 170, 171, 173 chaulmoogric acid  164, 165,170 chavicol methyl ether 42 Chebulic Myrobalans 151 Chenopodium album 82 Cherimolia 54 Cherokee Rose  33, 38 Cherry, Jerusalem 478 Chestnut Rose  29, 33 Chicoric acid 73 Chicory  48, 73, 129 China Rose 29 Chinese   Black Nightshade 466  Dandelion  74, 75, 76  Goldthread 171  Hawthorn 29  Holly 475  Lobelia  428, 430  Sage 146   Tea Rose 38  Wedelia  63, 65 chitinase E 436 Chlamydia pneumoniae  172, 178 trachomatis  208, 278 Chlamydophila pneumoniae 178 chloramphenicol  197, 445, 460 Chlorocebus pygerythrus 263 chlorogenic acid  73, 108, 356, 454 chloromycetin  197, 198 chloroquine  201, 220, 460 chlortetracycline 198 choline 70 Chondrodendron tomentosum 362 Chromobacterium violaceum 29 Chrysanthemum, Florist’s  180 Chrysanthemum leucanthemum 48 morifolium 180 segetum 180 sinense 180 chrysoeriol 171 chrysoplenetin  97, 98 chrysosplenol  96, 97, 98 cichoriin 73 Cichorium intybus  73, 129, 158 Cinchona  377, 388, 394 cineole  43–5, 95, 190, 314, 327  1,8-cineole  95, 327 cinnabarite 213 cinnamic acid 70 cinnamic aldehyde 43 Cinnamomum baileyanum 185 camphora  43, 178, 185 iners 185 laubatii 185 oliveri 185 propinquum 185 virens 185 zeylanicum  43, 178, 185 Cinnamon  29, 43, 67, 178, 211 ciprofloxacin 75 cis-chrysanthenol 108 cis-chrysanthenyl acetate  108 cisplatin  120, 128 Cissampelos pareira 185 Cistuscreticus 19 cis-β-farnesene 70 citral  44, 87 citrinin 443

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citronellal  44, 87, 95 citronellol  29–31, 33 Citrullus colocynthis 185 lanatus 185 vulgaris 185 Citrus aurantium  42, 44 aurantium subsp. bergamia 44 limon 44 reticulata 75 Cladanthus multicaulis 67 Clausena brevistyla 185 excavata 185 smyrelliana 185 sp. Tipperary  185 Claviceps purpurea 341 Clavija procera  182, 183 Clematis aristata 110 brachiata  111, 113 chinensis 114 cirrhosa  111, 113 dioica 113 Erect 112 flammula 114 glycinoides 110 hirsuta  111, 113 ligusticifolia  112, 113 microphylla 110 montana 113 oweniae  111, 113 papuasica  111, 113 pickeringii 133 recta  111, 113 sinensis 113 Small 110 virgiana 112 vitalba  110, 111 Western 113 Cleome droserifolia  115, 117 gynandra  115, 116, 117 hassleriana 116 rutidosperma 118 viscosa  114–6, 118 cleomin 115 Clerodendron traceyi 134 Clerodendrum floribundum 133 clinoptilolite  240, 242 clofazimine 160 Clonorchis spp.  280 Clostridium difficile 207 perfringens  199, 321 tetani 199 Clove  36, 43, 67, 319 Clove oil 43 cocaine  46, 341, 370 Coccidioides immitis 199 cochlearin 378 Cocky Apple  180, 181 codeine  22, 23, 38, 121, 341 Codonocarpus attenuatus  376, 377 australis 378 cotinifolius 376–8 pyramidalis 376 Coelospermum paniculata var. syncarpum 187 colchicine 130 coleon A  99, 101

Coleus 99 amboinicus 101 aromaticus 101 barbatus 101 coerulescens 101 kilimandschari 101 vettiveroides 102 Colocasia esculenta  439, 441 colupulone 333 Comfrey  48, 50, 51, 120 Commiphora myrrha 75 Common Broom  416, 417 Brushtail Possum 176 Daisy 48 Thornapple 350 coniine 415 Conospermum brachyphyllum 134 incurvum 134 convallamarin 27 Convallaria majalis  26, 27 convallarin 27 convallatoxin  26, 27 Convolvulus angustissimus 185 arvensis 185 clementii 185 crispifolius 185 erubescens 185 eyreanus 185 graminetinus 185 microcephalus 185 pluricaulis 152 recurvatus 185 remotus 185 tedmoorei 185 wimmerensis 185 Conyza aegyptiaca 186 canadensis 469 sumatrensis 186 Copi 267 Coptis chinensis 171 Coptotermes acinaciformis 301 formosanus 300 coramsine 476 Cordyceps sinensis 474 Cordyline terminalis 294 Coriander 43 coriandrol 43 Coriandrum sativum 43 Cork Oak 393 Cork-tree 393 Corkwood 379 Duboisia  381–3, 393, 395–8, 417 Australian 387 Laurel 394 Leichhardt  380, 393, 397 Corn Chamomile  66, 67 Corynebacterium diphtheriae 55, 56, 75 Corynocarpus laevigatus 295 Costus speciosus 449 Cotula tinctoria 67 coumarin  67, 70, 80, 84, 129, 185, 429 Crataegus cuneata 29 oxyacantha 28 pinnatifida var. major 29 Creeping Bentgrass  330

Crenidium spinescens 398 Cress Brazilian 53 Daisy  48, 52, 61 crocidolite 236 Crotalaria incana 92 Cryptocarya corrugata 134 Cryptococcus neoformans  96, 482 Cucumis melo 197 Cucurbita maxima 186 pepo 186 Culex quinquefasciatus 58 Curaderm  476, 477 curare  362–4, 382 Curcuma amada 159 australasica  159, 186 domestica  158, 186 longa  64, 158, 159, 186, 475 curcumene 44 curcumin 159 Curvularia lunata 103 cuscohygrine 359 Custard Apple 55 cyanide  243, 244 cyanidin 119 Cylas formicarius elegantulus 319 cymarin  25, 26 Cymbidium canaliculatum 419 Cymbopogon ambiguus  134, 315 Cyphanthera anthocercidea 398 odgersii 398 tasmanica  398, 399 cytisine  415, 416, 417, 418 Cytisus scoparius  416, 417 D dactinomycin 200 daidzein 443 Daintree ulcer  203 Daisy  10, 46, 55 Alpine 58 Common 48 Singapore  60, 62, 138 Sunflower  59, 61 Daisy Cress  48, 52, 61 Damask Rose  29, 30, 35 Dandelion  46, 48, 64, 70–7, 82, 158, 189 Chinese 74–6 Japanese 75 Russian  70, 77 dapsone  160, 170 dasyscyphin-C 65 Datura  341, 350, 356 Purple 346 White 346 Datura alba 347 arborea 395 fastuosa  354, 356 ferox  346, 350, 351, 356 inoxia  345, 346, 351, 356 leichhardtii  349, 350 metel  345–7, 350, 351, 356 metel var. fastuosa  346, 347 stramonium  346, 349–54, 357, 384 stramonium var. tatula 354 wrightii 350 daturamine 359 daunomycin 201

daunorubicin 201 Day Jessamine 488 DDS 160 DDT 58 Deadly Nightshade  342, 353, 355, 357, 383, 463 dehydrongaione  313, 314, 328 dehydrotomatine 455 dehydroxyserrulatic acid  328 delphinidin 477 deltonin 445 deltonine  435, 436 deltoside 436 dendrolasin  327, 328 Dendrolasius fuliginosus 328 deptropine 359 Desert Poplar  376, 377 Desert Sneezeweed 105 Desert Thornapple 349 desmethylwedelolactone 64 Devil’s Apple  477 Devil’s Fig  458, 459, 460, 483 D-galactosamine 57 D-germacrene 104 D-glucoside 459 DHEA 434 Di Long  287, 288 diamino-diphenyl-sulfone 160 Diamondback moth  116, 300 Dianella callicarpa 134 longifolia var. grandis 134 revoluta var. revoluta 134 dicaffeoyltartaric acid 73 2,4-dichlorophenol 123 Dictamnus dasycarpus 446 Didymotheca cupressiformis 378 dieldrin 237 Digitalis  25–8, 370, 488 purpurea  10, 24, 449 digoxin  225, 227, 449 dihydrocarveol 43 dihydrocarvone 43 Dill 43 dillapiole 43 dimaturin 329 dimerumic acid 441 dimethylnitrosamine 454 Diocirea microphylla 297 ternata 297 diosbulbin  437, 445 dioscin  435, 438, 440, 445–77 dioscorans 438 Dioscorea alata  434, 436, 441 alata var. purpurea 441 batatas  438–41, 444 birmanica 446 bulbifera  436–8, 442, 444, 445 bulbifera var. sativa 437 cayenensis  436, 439 cirrhosa 441 collettii  435, 445 collettii var. hypoglauca 445 composita  433, 435 deltoidea  433, 435 deltoidea var. orbiculata 445 dumetorum  438, 439 elephantipes 433 esculenta  441, 446 floribunda  433, 435 futschauensis 445

INDEX hispida  437, 438, 446 hypoglauca 437 macrostachya  432, 433 membranacea 446 mexicana 435 nipponica  440, 446 opposita  436–8, 441, 442 panthaica 440 polygonoides  439, 440 prazeri  433, 435 pseudojaponica  434, 442 septemloba  437, 440 spongiosa 440 spp.  439, 441–2 sylvatica 435 tokoro  435, 437, 438 transversa 444 villosa 439 zingiberensis  435, 441 dioscorealide 446 dioscoretine  438, 439 dioscorin 441 diosgenin  432–5, 437–42, 445–50, 452, 454, 461, 479 dipentene 44 dipyrone 54 Dirofilaria immitis 149 dl-hyoscyamine 341 Dodonaea angustissima 332 boroniifolia 331 falcata 331 filifolia 331 microzyga 332 physocarpa 337 spp. 334–7 triquetra 332 uncinata 338 viscosa  178, 269, 330–3, 339 viscosa subsp. angustifolia 333 viscosa subsp. angustissima 332 viscosa subsp. burmanniana 331 viscosa var. angustifolia  178, 337 Dog Rose 32 dopamine  122, 325, 428 Doryphora sassafras 134 Doughwood 393 Downy Thornapple 350 doxorubicin  148, 200, 201, 478 Drimia maritima 27 Drymaria cordata 186 Dryopteris crassirhizoma 319 Drypetes lasiogyna 134 DTO 23 d-tubocurarine 362 Duboisia arenitensis  380, 398 campbellii 380 hopwoodii  106, 372, 375, 376, 379–83, 389, 391, 392, 398, 402–4 leichhardtii  379, 380, 389, 393, 397, 398 myoporoides  358, 379–81, 383, 387, 389, 393–8, 401 duboisine  341, 386–90, 392 Duchesnea indica  474, 475 Dudo 163 Dudoa  163, 165 Dugong dugon 285 duingira 266 dulcamarine 471

E earthworm  286, 287 Giant Gippsland  289 Common  288, 289 ecdysteroids 435 Echinacea angustifolia 158 purpurea  158, 159 eclalbasaponin I  65 Eclipta alatocarpa 186 alba  56, 63, 64, 65, 186 platyglossa 186 prostrata  63, 64, 186 EDDS 469 EDTA  82, 469 Eggplant  451, 452, 455, 473, 476, 477, 485, 489 Ethiopian 473 Eglantine 29 Eisenia fetida 289 Elecampane 180 elemene 142 elemicin 44 elemol  313, 314, 328 Elephantopus mollis 186 scaber 186 spicatus 186 Elettaria cardamomum 39 cardamomum var. misicula 43 ellagic acid  128 Ellangowan Poison Bush 294, 311 Embelia schimperi 182 Emblic officinalis 151 Emu-bush  315, 323 Coccid 292 Silver 296 Weeping 316 Encosternum delegorguei 337 Endiandra sieberi  393, 394 Entamoeba histolytica  57, 109, 149, 155 Enterobacter aerogenes 471 Enterococcus faecalis  321, 337 Ephedra distachya 12 equisetina 12 intermedia 12 major subsp. procera 12 sinica 12 ephedrine  12, 341, 363 epi-ɑ-muurol 82 epicacalone  329, 330 Epidermophyton 54 epingaione  295, 328 epipinoresinol  312, 317, 325 epoxycembranediol 328 epsomite 240 eremolactone  315, 328 Eremophila  16, 131, 134, 297, 315, 318 abietina 323 alternifolia  183, 313, 325 beckeri 297 bignoniiflora  292, 313, 325 cuneifolia 313 dalyana 314 debilis 292 decipiens 329 deserti  294, 311 drummondii 324

duttonii  314, 321 elderi 314 fraseri  314, 321 freelingii  315, 323 gibbifolia 292 gilesii 315 glabra 297 hygrophana 293 latrobei  292, 311, 316, 318 latrobei subsp. glabra 316 linearis 321 longifolia  183, 292, 312, 316, 320, 325 maculata  292, 296, 309–12, 317, 324 maculata ‘Aurea’ 310 mitchellii  131, 292, 294, 297–9, 317 neglecta  318, 324 nivea 291 oldfieldii 292 paisleyi 318 racemosa 312 saligna 380 scoparia 296 Showy 312 Silky 291 spp. 327 sturtii 318 subteretifolia 291 virens 324 eremophiladienone 300 eremophilane  300, 325, 327, 329, 330 eremophilone  298, 299, 300, 317, 327 ergosterol 479 ergotamine 370 Erwinia carotovora 29 Erythrina indica 186 variegata var. orientalis 186 vespertilio  134, 186, 315 erythromycin  199, 483 Erythroxylum australe 370 coca 370 coca var. ipadu 370 coca var. truxillense 370 ecarinatum  370, 371 ellipticum 370 monogynum 371 ESBL 202 Escherichia coli  29, 36, 54–6, 80, 98, 121, 126, 132, 148, 150, 179, 181, 199, 202, 203, 205, 298, 305, 321, 337, 435, 471 coli IAM1264 244 esculetin  84, 126–30 esculoside 128 E-sesquilavandulyl 97 Essence de Bigarde 44 Essence de Portugal 44 estradiol 434 estrone 434 ethambutol 176 Ethiopian Eggplant 473 ethyl cyclohexane  177 ethyl-chaulmoograte 170 ethylene diamine tetra acetic acid  82, 469 etioline 477

545 Eucalyptus baileyana 136 botryoides 190 camaldulensis  190, 392, 422 camaldulensis subsp. obtusa 190 citriodora 190 coolabah subsp. arida 392 deglupta 190 globulus  36, 149, 190 grandis 190 maculata 190 major 136 nitens 36 pellita 301 populifolia 299 tectifica 268 tereticornis 190 Eucalyptus oil  44, 46, 89, 90 Eucommia ulmoides 325 eudesmane 327 eudesmol 327 Eugenia  91, 189 brasiliensis 186 reinwardtiana 186 eugeniin 36 eugenol  43, 44, 104 Euphorbia australis  132, 134 drummondii  132, 134 hirta 132 obovalifolia 454 peplus  131, 132, 186 Evodia, Pink-flowered 393 Evolvulus alsinoides 151 Excoecaria agallocha  131, 134 F Fagopyrum cymosum 475 faradiol 81 farnesene  44, 70, 104, 142, 149 farnesol  70, 142 Fasciola hepatica 483 Fasciolopsis spp.  280 fenchol 320 fenchone  44, 313, 327 Fennel  44, 313 Fenugreek  448, 450 Ferula communis 178 Fever-bark tree 394 Ficus brachypoda 454 racemosa 134 Field Poppy  19, 20 Field Rose 32 Fierce Thornapple 350 Fig, Devil’s  459, 460 Flammula Jovis  111 Flannel Bush 452 flatworm  279, 280 flavone  70, 314, 485 fluorouracil  35, 70, 128 fluke  280 intestinal 280 liver 280 lung 280 Schistosoma  109, 274, 280, 282, 283, 453, 483 sheep 149 Fly Agaric  123, 367 Foambark Tree  332 Foeniculum vulgare 44 Foetid Hellebore 486 Forest Red Gum  190 forskolin  102, 103

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Foxglove  10, 19, 24, 28, 449 Frankincense 75 fraxinol 429 Fraxinus bungeana 129 excelsior 129 rhynchophylla 129 freelingyne  315, 327 French Marigold  82, 83, 84 Frogmouth, Tawny  285 Fruit-salad Plant  96 frusemide 53 Fuchsia Native  309, 310, 315, 316, 317, 325 Rock  315, 323 fucosterol 479 furans  316, 327 furfural  70, 328 Fusarium  235, 482 moniliformis 55 oxysporum  55, 56, 103 G Gag-root 429 Galangal 184 Galanthus woronowii 364 gallic acid  29, 35,104, 306 Gan Cao 75 garlic  81, 107, 158, 174, 175, 231, 443 gazaniaxanthin 33 geebung 94 Gelsemium elegans 147 gemcitabine 128 geniposidic acid  313, 325, 327 genistein 443 gentamicin  121, 179 Gentiana lutea 487 gentisic acid  306 geophagy  246, 261, 264, 265, 270, 273–5 Geraldton Wax  94, 95 geraniol  29, 30, 31, 70, 95 geranyl acetate  44, 327 germacrene  97, 104, 142 germacrene D  97, 104 German Chamomile  66, 67, 81 German Chamomile oil 67 Geum 36 japonicum  36, 37 talbotianum 37 urbanum 37 Giardia intestinalis 109 gibberellic acid 397 gidyea  373, 374 Ginger  44, 46, 443, 449 6-gingerol 443 gitogenin 447 Glebionis segetum 180 globulol 300 Glomus claroideum 469 intraradices 469 Glossocarya calcicola 134 glucocapparin  115, 116 glucocleomin 116 Glycine max  448, 480 glycitein 443 Glycocystis beckeri 297 Glycyrrhiza uralensis  75, 346 Godi 163 Golden Marguerite 67 Golden Seal  171 Goldenrod Atlantic 180

Canada 180 Gonococcus vaginalis 39 Goodenia bellidifolia 422 glauca 422 Hairy 422 Hop 422 lunata  392, 422 ovata  421, 422 scaevolina 422 Gorilla beringei beringei 262 gorlic acid 165 Gotu Kola  81, 137, 138, 140–4, 146–9, 151, 155, 158, 428 gout  129, 130, 442 gracillin  435, 445 Grammosolen dixonii 398 Granadilla 421 Great Blue Lobelia 426 Green Cestrum  488, 489 Green Hellebore 486 Green Poisonberry 488 Green-berry Nightshade  465 Grevillea juncifolia 134 pteridifolia  134, 201 robusta 134 stenobotrya 392 striata  134, 392 g-strophanthin 488 Guaiacum officinale 178 guaiazulene  69, 70 Guayule 77 Guduchi 151 Gum Blue 190 Forest Red  190 River Red  190 Gynandropsis gynandra 117 gynocardase 168 Gynocardia odorata 164 gynocardin  165, 167, 168 gypsum 229 Gyrocarpus americanus 382 jacquini 382 Gyrostemon australasicus 378 ramulosus 378 tepperi 378 H Haemodorum simplex 134 Hairy Goodenia 422 Hairy Thornapple 350 halloysite 227 Hansen’s disease  157 harman 412 Hawthorn  28, 29, 130 head lice  57, 412 Headache Vine  110 Hechtia texensis 448 hecogenin 447 Heicoverpa armigera 337 helenalin 59 Helichrysum umbraculigerum 191 Helicobacter pylori  55, 69, 151, 172, 474 Heligmosomoides polygyrus  80, 281 Heliopsis longipes 57 heliotropin 43 Hellebore  486, 487 Black  486, 487 Foetid 486

Green 486 White  486, 487 helleborein 486 helleborin 486 Helleborus foetidus 486 niger  486, 487 hellebrin 486 helminths  14, 275, 278, 279, 290 Helopeltis theivora 58 Hemlock 146 Henbane  346, 358, 384, 394, 463 Black  341, 342, 348 White 348 heneicosane 30 Henna  39, 69 herniarin  67, 80 heroin 22 Herpes genitalis 69 simplex  36, 76, 81, 97, 100, 145, 191, 484, 485 Herpestris monniera 150 Heterodera zeae 87 Heterometrus indicus 65 Hevea brasiliensis 77 hexatriacontane 30 Hibiscus rosa-sinensis 83 tiliaceus 186 trionum 186 vitifolius 186 Hippobroma longiflora 427 Holly, Chinese 475 Homalanthus nutans 131 honey ants  268 hookworm  14, 266, 271, 274–6, 280 Hop Goodenia 422 Horsechestnut  124–8, 137 Horseradish 378 Horseweed 469 Hop-bush Brilliant 332 Common 332 Large-leaf 332 Slender 332 Thread-leaf 331 Huang Lian  171 Humulus lupulus  178, 320, 332 huntite  248, 249 hydnocarpic acid  165 hydnocarpin  170, 171, 172 Hydnocarpus alcalae  163, 165 alpina 164 annamensis 170 anthelmintica  163–5, 170, 171 castanea 163 ilifolia 164 kunstlerii 163 kursii 163 kurzii  164, 165 laurifolia  163, 165 macrocarpa 163 octandra 164 odorata 164 pentandra  161, 163, 170 venenata  163, 164 wightiana  163–5, 170, 171 Hydnocarpus oil  169, 170 hydnowightin  170, 171 Hydrastis canadensis 171 Hydrocotyle

asiatica 137 bonariensis  138, 139 cordifolia 137 leucocephala 139 sibthorpioides 139 hydrocyanic acid  168 hydrocyanide  169, 311 hydrotalcite  238, 240 hydroxycalamenene 327 hygrine 398 Hymenolepis diminuta 281 nana 57 hyoscine  341, 349, 351, 356, 358, 370, 389, 394–8, 400, 402 hyoscyamine  18, 341, 344, 346, 349, 352, 355–9, 366, 384, 387, 389, 390, 394–400, 463 Hyoscyamus albus 348 niger  341, 342, 348, 353, 358, 384, 463 Hypericum  81, 186 gramineum 186 japonicum 186 perfoliatum  81, 428 pusillum 186 hyperoside  28, 338 hypoxanthine 130 I ibotenic acid 368 Ilecis 475 Ilex cornuta 475 Ilicis cornutae 475 Illicium verum 42 illite  202, 203, 221, 263 Ilpara 392 Indian Borage  100 Indian Horsechestnut  126 Indian Lobelia 424 Indian Snakeroot 10 indioside D 461 indole-3-carboxylaldehyde 66 indomethacin  54, 57, 74, 81, 481 Intal 151 Inula helenium 180 inulin  74, 77 Ipomoea batatas 327 digitata 151 purga 178 isobrahmic acid  143 isoelemicin 44 isoeugenol 44 isohydnocarpin 171 isolobelanine 428 isolobinine 425 isomenthone  45, 316, 320 isomyodesmone 328 isoniazid  174, 176 Isoodon obesulus 285 isoquercitrin 73 isosolafloridine 454 isothakuniside 143 Isothankunic acid  143 Isotoma anethifolia 425 axillaris 425 hypocrateriformis 427 longiflora 427 petraea  134, 424, 426 Isotome, Rock  424, 426, 427 Ixodes holocyclus 412

INDEX J Jacksonia scoparia 134 Jagera pseudorhus 332 Jalap 178 Jambul 178 Japanese Dandelion 75 Japanese Peppermint oil 45 Japanese Scopolia 360 Japanese Yam  435, 437 Jatamansi 151 Javan Ash  166 Jerusalem Cherry 478 Jessamine  146, 487, 488 American Yellow  147 Day 488 jetrorrhizine 112 Jimson Weed  349, 352 Juniper, Native  293 Juniperus communis 178 excelsa 178 procera 178 sabina 105 K kaempferol  40, 119, 120, 142, 334, 356, 471 kakadumycin 201 Kalaw 163 Kallstroemia pubescens 448 Kangaroo, Grey 285 Kangaroo Apple  452, 454, 456 kaolin  214–6, 220, 221, 226, 227, 236, 247, 255, 263, 266, 272, 273 kaopectate  215, 216 karahanaenone  316, 320 Karaka 295 kaurenoic acid  54, 55, 56, 57, 61, 62, 66 Kemiri nut  156 Kennedia nigricans  134, 201, 202 Kerosene Wood  370 Khaki Bush 86 Klebsiella pneumoniae  81, 103, 132, 330 kohl  208, 209, 232 Kohoho 457 Kohuhu 178 Kombe 26 L Laburnum anagyroides 416 Lactobacillus plantarum 37 Lactuca virosa 470 lactucarium  469, 470 Ladanum 19 Lampito mauritii 288 Large-leaf Pennywort  138 Laudanum  19, 20, 23 Laurelia novae-zelandiae  176, 177 sempervirens 177 Laureliopsis philippiana 177 laurionite  209, 210 Lavender  29, 81, 145 Lawn Marsh Pennywort  139 Lawsonia inermis 39 lead poisoning 231 ledene 82 leech  106, 107 Leichhardt Corkwood  380, 393, 397 Leishmania  54, 101, 274, 483 amazonensis  101, 120, 139 braziliensis 57 donovani 172

Lemon  40, 44, 131 Lemon Balm  145, 178 Lepidosperma viscidum  134, 324 Leptospermum petersonii 134 Leptospira 277 Leucojum aestivum 364 levartenol 121 lice  322, 435 head  57, 412 lichen  39, 258 lidocaine 371 lignocaine 371 Ligularia macrophylla 300 Ligustrum lucidum 64 Lillypilly  91, 420 Lily-of-the-Valley  19, 26, 27, 28 limonene  43–5, 85, 87, 95, 313, 314, 316, 320, 327 linalol 44 linalool  30, 33, 43, 95 linalyl acetate 44 linarin 179 linoleic acid  34, 37, 118, 328 linolenic acid  34, 37, 118, 485 linolic acid  164 Lippia chevalieri 53 Liquorice  44, 75, 346 Listeria monocytogenes  104, 321 lithospermic acid  146 Lithospermum erythrorhizon 146 Litomosoides sigmodontis 281 littorine  390, 398 Liv-52 158 L-lysine 418 lobelaine 428 lobelanidine  427, 428 lobelanine  418, 428 Lobelia American Torch 423 Blue 423 Chinese  428, 430 Edging 423 Great Blue 426 Indian 424 Mexican 423 Pale-spike 426 Poison 429 Lobelia angulata 430 arenaria 430 arnhemiaca 423 cardinalis 425 chinensis  428, 429, 469 concolor 429 darlingensis 429 erinus 423 excelsa 424 inflata  418, 424–8, 431 laxiflora  423, 429 macrodon 430 membranacea 423 nicotianifolia  424, 425 nummularia 430 pedunculata 430 pratioides 429 purpurascens  429, 431 siphilitica  425, 426 spicata 426 tupa 423 lobelidine 425 lobeline  418, 424, 425, 428 Lobster Flower 103 Long Yam  444, 445

Lophomyrtus bullata 178 Lophophora williamsii 416 lovastatin  441, 443 Lucilia sericata 87 Luffa aegyptiaca 186 cylindrica 186 graveolens 186 lumbricin I  288 Lumbricus rubellus 288 terrestris 289 lumbrokinase 288 lunasin 473 lupanine  220, 417 lupeol  76, 171, 338, 481 lupinine 417 Lupins 415 lutein  85, 86, 142 luteolin  54, 56, 62, 65–7, 69, 70, 73, 76, 120, 171–3, 312, 325, 326, 429 luteolin 7-glucoside 76 luteolin 7-O-glucoside  65 Lycopersicon esculentum  455, 489 Lygodium flexuosum 186 japonicum 186 microphyllum 186 reticulatum 186 lysine  415, 417 M Ma Huang 12 Macaca mulatta 224 Macadamia integrifolia 135 Macrophomina 482 Macropus agilis 285 fuliginosus 285 giganteus 285 rufogriseus 285 Madagascar Periwinkle  10, 185 Madar 170 madasiatic acid  142 madecassic acid  140, 142, 143 madecassol  142, 149, 155 madecassoside  140, 142–4, 148, 149 Magic Ophthalmia cure  107 Makulu 163 malachite  205, 206, 207 Malaria  33, 57, 58, 87, 101, 102, 109, 111, 116, 134, 149, 153, 172, 185, 189, 201, 277, 287, 288, 336, 460–2 malic acid  32, 85 Mallotus mollissimus 187 philippensis 183 philippinensis 187 spp. 187 Mamane 416 Mandarin Orange 75 Mandragora autumnalis 344 caulescens 344 chinghaiensis 344 officinarum  342, 343, 359 turcomanica 344 Mandrake  342–6, 353, 358 Himalayan 344 True 359 Turkmenian 344 Mangifera

547 indica  148, 187 odorata 187 mangiferin  148, 185 Mango Ginger 159 Mangrove Black 182 River 182 Mangrove worm  267 mannitol  313, 314, 328 maokinine 13 Mapania microcephala 202 Marigold  78, 80, 81, 83, 85, 141 African  84, 85 Aztec  83, 84, 87 Corn 180 French 82–4 Marsilea drummondii 372 maslinic acid 37 Masto 301–3 Mastotermes darwiniensis 301–3 Matai 295 Matricaria chamomilla 66 recutita 66–8 matricarin 70 matricine 69 mekocyanin 19 Melaleuca leucadendra  187, 190 leucadendron 187 Melanthera biflora 60 integrifolia 60 Melia azedarach 184 Melicope elleryana 393 Melipona quadrifasciata anthidioides 55 Melissa officinalis  145, 178 Mentha arvensis  178, 179 canadensis var. piperascens 45 spicata  145, 178 x piperita  45, 145, 173. 178 menthofuran 45 menthol  45, 46 menthone  45, 320 menthyl acetate  45 Mescal Bean 416 mescaline 417 Mesquite 222 metahalloysite 215 metanicotine 396 meteloidine  351, 356, 370, 398 methicillin 207 methoxyeugenol 44 methoxyhydnocarpin 171 methyl anthranilate 44 bromide  116, 234 chavicol 84 eugenol 328 halide 234 thymol 104 methyleugenol  44, 316, 320 methylglucosinolate 115 mevinolins 443 Mexican Lobelia 423 Tarragon 84 Thyme 100 Yam  432, 433 Micrococcus flavus 334

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

luteus  205, 334 tetragenus 98 Microcyclus ulei 77 Microsporum  50, 56, 97 canis 103 gypseum  56, 97, 103, 335 Miliusa balanse 97 Milk Thistle  117, 129, 368 Milkweed 131 Milkwood 316 Milky Mangrove  131 Milky Plum  93, 94 Mimosa diplotricha 187 invisa 187 pigra 187 pudica 187 Mint, Variegated  99 miraxanthin V  122 Mirbelia oxylobiodes 135 mitchellene 317 mite honeybee 58 house dust  280 red spider  99, 116 scabies 322 mitomycin 201 Mock Strawberry  474, 475 Moluccella laevis 91 Momordica balsamina 187 charantia  178, 187 cochinchinensis 187 monacolin K  440, 441, 443, 444 monascin  441, 443 monascorubrin 444 Monascus pilosus 443 purpureus  441, 442 Monkshood  10, 212 monoamine oxidase  56 montera 375 montmorillonite  212, 221, 225–7, 271 Morinda citrifolia  135, 187, 467  spp. 187 umbellata 187 morphine  19, 21–3, 70, 149, 151, 152, 177, 192, 335, 341, 388, 394, 395 Mosqueta Rose 34 Moth, Diamondback  116, 300 Mountain Kangaroo Apple 454 Mountain Pratia 430 MRSA  36, 104, 134, 148, 155, 172, 179, 181, 192, 201, 202, 207, 321, 324, 334 Mud wasp  268 Mulga 426 multiflorin A  40 mumie 260 munumbicin  134, 201 muscaflavin  123 muscapurpurin 123 muscarubrin 123 muscovite 236 Mushroom Death Cap  368 Oyster 443 Termite 305 Mycobacterium africanum 175

avium 285 avium paratuberculosis 175,199 bovis  175, 176, 281, 285, 286 fortuitum  181, 183, 318, 324 indicus pranii 286 leprae  153, 155–8, 165, 170, 175, 278 lepromatosis  175, 278 marinum 202 microti 175 phlei 92 smegmatis  56, 176, 181, 183, 202, 324, 334 tuberculosis  55, 75, 104, 155, 159, 170, 174–6, 178, 182, 191, 201, 205, 334 ulcerans  175, 202–4, 286 myodesmone  311, 328 myoporone  300, 311, 316, 317, 328 Myoporum acuminatum  294, 327, 380 bontioides  295, 300 crassifolium 296 debile  292, 294 deserti  294, 300, 311, 321 floribundum 294 insulare  292, 293 laetum  178, 295, 296, 309, 312 montanum 294 parvifolium 293 petiolatum 294 platycarpum  308, 313 pubescens 296 sandwicense  294, 295 Slender 294 tenuifolium  295, 296 viscosum 294 myrcene  142, 313 Myriogyne minuta  105, 107, 108 Myristica fragrans 44 myristicin  43, 44 Myrmecobius fasciatus 303 Myrrh 75 myrtenal 108 myrtenol 108 myrtenyl acetate 108 myrtine 398 N N,N-dimethyltryptamine 417 N-alkylamides 57 narcotine 23 Nardoo 372 Nardostachys jatamansi 151 Nasturtium 86 Nasutitermes corniger 305 graveolus 302 triodiae 302 Native  Box 123  Currant 464  Olive 123  Pepper 454  Ragwort 420  Thornapple  349, 350  Tobacco  372, 379, 402–4, 431 Necator americanus  274, 276, 280, 281 Neem  39, 164 Neisseria gonorrhoeae  113, 172, 472 meningitidis 75 Nelumbo nucifera 39

nematode  80, 87, 281 neohydnocarpin  170, 171 Neolitsea dealbata 135 neomycin 198 neoxanthin 142 nepetin 313 nepetoidin A  104 Nerium oleander  26, 212 nerol  29, 30, 31 nerolidol  44, 70 Ngaio  178, 295, 309, 312 ngaione  311, 312, 316, 327 niacin  130, 274 Nicotiana alata var. persica 411 amplexicaulis 407 benthamiana 405–7 bigelovii  410, 412 burbidgeae 407 cavicola  406, 407 debneyi 407 excelsior  403, 405, 407 fruticosa 410 glauca  405, 407, 409, 489 goodspeedii  405, 407 gossei  405, 407 heterantha 407 maritima 407 megalosiphon  406, 407 megalosiphon subsp. megalosiphon 406 occidentalis  406, 407 persica  410, 411 quadrivalvis 410 repanda 410 rosulata 408 rosulata subsp. ingulba 406 rotundifolia 409 rustica  406, 410–2 simulans 409  spp. 405 suaveolens  376, 389, 403, 404, 409 sylvestris 409 tabacum  403, 405, 406, 409, 410, 412, 422 tomentosa 411 truncata 409 umbratica 409 velutina  404, 405, 409 wuttkei 409 nicotine  227, 361, 366, 388, 389, 391, 395, 396, 398, 403, 404, 406, 407, 409, 410, 412, 414–6, 422, 425, 428 nicotinic acid 415 Nierembergia veitchii 489 Nigella sativa 320 Nightshade American  451, 464–6, 482–4 Black  451, 455, 464–6, 464–74, 483 Brazilian 451 Chinese Black 466 Felty 457 Green-berry 465 Silver-leaf 452 Spiny 452 Sticky  453, 470 Stinking 463 Velvet 461 White  474, 483 Woody  470, 472

Woolly 465 Nipple Fruit  460 Nippostrongylus brasiliensis 281 Nocardia asteroides 200 mediterranea 200 nonadecane  30, 31 noradrenaline  121, 325 noraporphine 177 noratropine 389 norcoridine 177 norepinephrine  12, 121 norharman 412 norhyoscyamine  389, 396, 398 nor-lobelaine 428 nornicotine  391, 395, 396, 398, 406, 407, 412, 415, 416 nor-wedelolactone 64 noscapine  22, 23 novocaine 371 Numbat 303 Nut, Betel  116, 372, 373, 392 Nutmeg 44 Nux Vomica  47 O Oak, Cork 393 Oak-leaf Thornapple 349 ocimene  85, 87  (Z)-β-ocimene 104 Ocimum sanctum  64, 178 scutellarioide 99 1-octen-3-ol 104 Odontotermes formosanus 268 oestradiol 123 oestrogen  434, 441 Oil Anise 42 Bastard Sandalwood 131 Bergamot 105 Bitter Orange  44 Bitter Orange Flower 44 Calendula 80 Camphor 43 Cardamomum 43 Celery Seed  105 Chaulmoogra  161, 162, 163, 164, 169, 170, 173 Cinnamon 43 Clove 43 Coriander 43 Dill 43 Eucalyptus  44, 46, 89, 90 Fennel 44 German Chamomile 67 Ginger 44 Hydnocarpus 169 Japanese Peppermint 45 Lemon 44 Nutmeg 44 Orange  41, 44 Oregano 105 Peppermint 45 Rose  29, 30, 31 Savin 105 Spanish Sage  105 Sweet Orange  44 Old Man Weed  105, 108 Oldenlandia diffusa 475 Oleander, Climbing  25, 449 oleandrin 337 oleanene 338 oleanolic acid  56, 80, 338

INDEX oleic acid  34, 118, 165, 328 Olibanum 75 Oligoceros haemorrhages 328 Onchocerca volvulus 454 Oncoba echinata 163 Oncomelania hupensis 109 Onion, Sea 26 opium  18–23, 109, 362, 370, 373, 388, 469, 470 Oplopanax horridus 178 japonicus 328 oplopanone 328 Orange  40, 42, 44, 488 Orange Cestrum 488 Orange oil  41, 44 Ordeal Bean 361 Oregano, Cuban  100 Oregano oil  105 Oreganum vulgare subsp. vulgare 105 ornithine 415 ouabain  25, 488 oxacillin 36 oxytocin  116, 435 P Pacific Yew 10 paclitaxel 447 Pademelon, Tasmanian  285 Paecilomyces varioti 335 palmatine 112 palmitic acid  34, 37, 118, 165, 328 paludolactone 56 palygorskite  215, 225, 228, 240 Pan troglodytes 262 Panax ginseng 444 notoginseng 474 Pandanus aquaticus 373 Pangium edule  168, 169 Papaver aculeatum  20, 21 argemone 20 dubium 20 horridum 21 hybridum 20 rhoeas  19, 20 somniferum  19, 20 somniferum subsp. setigerum 20 somniferum subsp. somniferum 20 papaverine  22, 69 paracetamol  57, 115, 227, 228 Paragonimus sp. 280 Paramphistomum cervi 149 paraquat 240 paregoric 20 parillin 450 Parmelia perlata 39 Parthenium argentatum 77 parvifloron  104 Pascalia glauca 61 Passiflora foetida 187 quadrangularis 421 spp. 187 patuletin  67, 78 Pediculus humanus 57 pelletierine  398, 417, 418 penicillin  11, 91, 191, 194–9, 202, 321 penicillinase 321 Penicillium  193, 194, 196, 198 camemberti 198

chrysogenum  195, 196, 197 glaucum 196 janczewskii 199 notatum  195, 196 roqueforti 198 Pennywort Brazilian 139 Large-leaf 138 Lawn Marsh  139 Whorled 139 Pentacoelium bontioides 297 pentacosane 30 pepino 483 Pepper, Black  417 Pepper Vine  112, 113 Peppermint  45, 145, 173, 178 Perionyx excavatus 288 Periploca graeca 449 nigrescens 449 Periwinkle, Madagascar  10, 185 Persian Rose 35 Persian Tobacco 410 Persoonia falcata  92, 93, 94 juniperina 92 pinifolia  92, 93 salicina 92 Peyote 416 phellandrene 43 Phellodendron amurense 474 phenyl ethyl alcohol 29 phillyrin 312 Pholidia scoparia 296 phosgenite  209, 210 Phyllanthus fraternus 64 niuri 64 phyllygenin 312 phyoxolin 108 Physalis angulata 187 spp. 187 Physostigma venenosum 361 physostigmine  359, 361–6, 368, 386, 449, 472 phytic acid  270 Phytolacca dodecandra 223 Phytophthora 482 piceine 317 Pigweed 118 Pimelea prostrata 131 Pimpinella anisum 42 pinene  43, 44, 314, 327 Pink Brownii  95 Pink Cauliflower  95 Pink-flowered Evodia 393 pinoresinol  312, 325 pinworm 280 Piper betle 372 nigrum 417 piperidine  415, 417 piperine 417 piperitenone  85, 87 Pitcherry 372 Pitchiri 372 Pithera 391 Pittosporum hirtellus 135 phylliraeoides var. microcarpa 135 tenuiflorum 178

Pituri  106, 318, 369, 370, 372–6, 378, 381, 383, 388, 391, 392, 395, 396, 398, 402–4, 406, 418, 420, 426, 431 Rock  405, 407 Sandhill  406, 408 Planchonia careya  135, 180, 181 Plantago ovata 480 plantolin 108 Plasmodium falciparum  87, 97, 102, 109, 116, 134, 172, 201 vivax 460 Platycodon grandiflorum 474 Plectonema boryanum 244 Plectranthus amboinicus  100, 101, 103, 104, 156 apreptus 100 argentatus 100 aromaticus 101 barbatus 100–4 coleoides 103–5 congestus 99 cylindraceus  103, 104 diversus 135 ecklonii 104 elegans 104 foetidus 100 forskohlii 101 fruticosus 103–5 grandidentatus 104 grandis  101, 104 graveolens 100 habrophyllus 135 heretoensis 104 incanus 104 laxiflorus 156 madagascariensis 99 melissoides 104 neochilus  103, 104 ornatus  103, 104 parviflorus 100 saccatus 99 scutellarioides 99 vetiveroides  102, 156 Pleuranthodium racemigerum 184 Pleurotus ostreatus 443 Plum, Brown  370, 371 Plum-tree, Native  316 Plutella xylostella  133, 300 Podargus strigoides 285 Podocarpus grayae 135 Pohutukawa 178 Poison Lobelia 429 Poison Pratia 429 poliumoside 315 Polyalthia australis 202 michaelii 202 nitidissima 202 patinata 202 polygalacic acid 50 Polygonum bistorta 446 Polysaccum olivaceum 250 Poporo 457 Poppy Bristle 20 Field  19, 20 Long-headed 20 Opium  19, 20, 21 Pale 20 Rough 20

549 Populeon 348 Poroporo 457 Portulaca bicolor 119 grandiflora  119, 122 oleracea  122, 123, 188 pilosa  119, 120  spp. 188 quadrifida 122 tuberosa 123 Potato  220, 221, 319, 455, 458 Potato Rose 32 Potato Tree 461 Pratia angulata 430 arenaria 430 Chatham Island 430 macrodon 430 Mountain 430 nummularia 430 pedunculata 430 Poison 429 Purple 429 White Star 430 Pratylenchus pratensis 87 Premna serratifolia 135 Presbytis rubicunda 262 Prezwalskia tangutica 359 Prickly Fanflower 377 procaine 371 progesterone  432, 433 Propionibacterium acnes  29, 205, 322 Propolis  55, 81 propyl gallate 128 proscillaridin 26 Prosopis juliflora 222 pallida 222 Prostanthera rotundifolia 135 prostigmin 363 prostratin  131, 134 Proteus vulgaris  56, 121 protocatachuic acid  306 protodioscin  440, 477 protoneodioscin 445 protoneogracillin 445 Provence Rose 38 Prumnopitys taxifolia 295 prunasin  311, 312, 317, 328 Prunella vulgaris  145, 446 Prunus sargentii 36 Psacalium compositum 329 decompositum 329 radulifolium 330 sinuatum 329 Pseudocanthotermes spiniger 305 Pseudocheirus peregrinus 204 Pseudomona fluorescens 98 Pseudomonas aeruginosa  29, 56, 75, 80, 121, 132, 148, 199, 202, 205, 206, 298, 321, 334, 337, 435 aureus 56 maltophilia IAM 1554 244 pyocyanea 92 Pseudopanax crassifolium 178 pseudopelletierine 418 psi-taraxasterol 81 psilocin 341 Psilocybe mexicana 341 Psoralea 374

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Psoroptes cuniculi 87 Psydrax oleifolia 91 Psyllium 480 Pterigeron odorus 88 Pterocaulon alopecuroides  96, 97 balansae 96 glandulosum 96 globuliflorus 88 globulus 96 nivens 96 polystachyum  96, 97 redolens 96 serrulatum  88, 96, 420 sphacelatum  88, 96, 97, 135, 182, 324, 420 spheranthoides 96 verbascifolium 96 Pukatea  176, 177 pukateine 177 Pukeweed 424 pulegone 45 Punica granatum 418 Purple Pratia 429 Purslane 118–23 Pygmaeopremna herbacea 446 pyrazinamide 176 pyrethrin 300 pyrogallol-5–carboxaldehyde 37 pyromorphite  232, 272 pyrrolidine 415 Pythium ultimum  56, 201 Q Quaker Laudanum 20 quassinoid  172, 184 quercetin  35, 67, 69, 70, 97, 119, 120, 142, 313, 338, 356, 429 Quercus suber 393 quinine  220, 224, 341, 377, 388, 394, 460 R rabdosiin 146 radioiodine 240 Radium Weed  131 Radula marginata 191 radulifolin 330 Raillietina echinobothrida 149 Ramarama 178 Rauvolfia serpentina 10 Red Cestrum 487 Red Mold Dioscorea 441 Red Root Gromwell  146 Red Yeast Rice 440–4 Rescue Remedy  48, 111 Rhamnus cathartica 178 Rheum officinale 178 Rhizoctonia solani  56, 335 Rhodotorula rubra 56 Rhoeadine 19 Rhus javanica  36, 184 Rice, Red Yeast  440, 442, 443 Ricinus communis 188 rifampicin  160, 176 rifamycin 200 ringworm  102, 160, 187, 322, 347, 356, 382, 407, 459, 465 scalp 415 River Red Gum  190 Rock Isotome  424, 426, 427 Rock Pituri  405, 407 Roman Chamomile  66, 67, 68, 81 Rooibos tea  172 Rosa

arvensis 32 canina 32–7 centifolia  29, 35, 36, 38, 39 chinensis  29, 38 damascena  29, 30, 33–6, 38 davurica  33, 35 dumalis 33 eglanteria  29, 34, 36 gallica  29, 30 laevigata  33, 36, 38 micrantha 32–5 mollis 32 multiflora  29, 33, 35, 39, 40 pisiformis  33, 34 pulverulenta  33, 34 roxburghii  29, 33 rubiginosa  33, 34 rugosa  32, 35–8 sempervirens  33, 36 villosa  33, 34 rosamultin 36 Rose Cabbage 38 Cherokee  33, 38 Chestnut  29, 33 China 29 Damask  29, 30, 35 Dog 32 English Tea 33 Field 32 Mosqueta 34 Multiflora  33, 35, 39 Persian 35 Potato 32 Provence 38 Rose absolute 31 Rose oil  29, 30, 31 Rose Otto 31 Rose water 31 Rosehips  32, 33, 34 Rosemary  144, 145 rosmarinic acid  51, 102, 104, 143–6, 179 Rosmarinus officinalis 144 Ross River fever 203 roundworm  14, 165, 279, 337 American Racoon 275 Canine 276 Giant Intestinal 280 rubidomycin 201 rubixanthin 33 rubropunctatin 444 Rubus spp. 188 rufocromomycin 201 Russian Dandelion  70, 77 rutin  28, 128, 142, 330, 338 Ryparosa amplifolia 167 anterides 167 javanica  166, 167 kurrangii  166, 167, 168 kurzii 167 maculata 167 maycockii 167 milleri 167 sp. Daintree  167 wrayi 167 S sabinene  44, 316, 320 sabinyl acetate  104, 105 Saccharomyces cerevaceae 148 cerevisiae  195, 334

safrole  42–4, 177, 316, 320, 328 Sage  98, 145, 178 Chinese 146 oil, Spanish  105 Saguinus mystax 262 sakuranetin 338 Salacca zalacca 262 Salak 262 salbutamol 482 Salmonella enterica serovar. typhimurium 202 group C 56 paratyphi  56, 148 typhi  35, 36, 55, 56, 121, 148, 334, 465 typhimurium  35, 36, 132, 148, 298 salvanolic acid  146 Salvia chinensis  474, 475 lavandulifolia 105 miltiorrhiza  146, 475 officinalis  145, 178 Sambucus williamsii 325 Sandalwood Bastard  131, 294, 297–9, 306, 317 Red  298, 308 Sandhill Pituri  406, 408 Sanguinaria canadensis 178 Sanguisorba officinalis 178 santalcamphor  298, 300 Santalum acuminatum 299 cygnorum 298 lanceolatum 135 obtusifolium 393 Santolina chamaecyparissus 180 sapogenin  432, 433, 435, 439, 440, 447 Sapucainha  163, 173 Sarcina lutea 148 Sarcoptes scabiei 323 sarmentogenin 449 Sarsaparilla 482 sarsapogenin 448 sarsasapogenin  449, 450 Savin oil 105 SC-1, SC-2 482 scabies mite  322, 458 Scaevola spinescens  135, 377 Schinopsis balansae 220 Schinus molle 58 Schistosoma  109, 274, 283, 453 haematobium  280, 282 intercalatum 282 japonicum 282 mansoni  281–3, 483 mekongi 282 schistosomiasis  278, 282 schizanthines 390 Schizanthus grahamii 391 Scilla maritima  26, 27 scillaren 26 scillarin A 27 Scolopia braunii 135 scoparone  84, 429 scopolamine  341, 346, 349, 352, 354–6, 358, 359, 366, 370, 387, 389, 390, 395, 398–401, 463 scopolamine butylbromide 353 scopoletin  345, 356, 359, 483

Scopolia carniolica  359, 360 Japanese 360 japonica  359, 389 lurida  359, 360 podolica 360 tangutica 359 scopolin 356 Scute 287 Scutellaria baicalensis 287 barbata 475 Sea Onion 26 Sea Purslane  120 Senecio aegyptius var. discoideus 330 nemorensis. 330 spp. 330 sepiolite  225, 228, 271 sesquithuriferone 300 Sesuvium portulacastrum 120 Shan Yao  436, 441 Shepherd’s Purse  19, 185 Shigella  56, 75 boydii  56, 148 dysenteriae  56, 121, 148 flexnerii 148 sonnei 56 shilajit  260, 261 Sida cordifolia 188 silibinin 368 Silkworm 284 Silver-leaf Nightshade 452 Silybum marianum  117, 368 Singapore Daisy  60, 62, 138 Sisal  433, 447 sitosterol  65, 142, 459, 480, 483 Skullcap  Barbat  474, 475  Chinese 287 smectite  202, 203, 215, 217, 221, 224, 227, 253, 263, 272, 273 Smelly Bush 88 smilagenin 450 Smilax 482 aristolochiaefolia 450 corbularia 446 glabra 446 regelii 482 Smyrnium olusatrum 71 Snakegourd 75 Snakeroot, Indian 10 Sneezeweed  105–8, 110, 420 Desert 105 Sneezewort, Australian 50 Snowdrop, Caucasian  364 sobatum 479 sodium aescinate  126 solacallinidine 454 sola-dunalinidine 454 solamargine  435, 453–5, 459, 460, 462, 465, 473, 476–8, 482–5 Solandra grandifolia 390 longifolia  389, 390 maxima 390 solanidine  455, 465 solanine  220, 341, 455, 460, 462, 463, 471, 472, 473, 479, 481, 489 solanogantine 485 Solanum aethiopicum 473 americanum  451, 464–6, 482–4

INDEX atriplicifolium 472 aviculare  452–7, 482 callium 454 capsiciforme 454 chrysotrichum  482, 484 crinitum 478 densevestitum 457 dulcamara  189, 455, 463, 464, 470–3 echinatum 490 eleagnifolium 452 ellipticum 420 erianthum  461, 462 fendleri 220 frutescens 472 giganteum 485 glaucophyllum 489 hispidum 482 incanum  452, 454, 472, 477, 482, 483 indicum 452 jamesii 220 khasianum 452 laciniatum  452, 453, 456 lasiocarpum 452 lasiophyllum 452 linnaeanum  475, 476 lycocarpum  453, 478, 483 lyratum  473–5, 483 macrocarpum 459 malacoxylon 489 mammosum  452, 460, 461 marginatum  452, 486 mauritianum  420, 421, 456 melongena  451, 455, 472, 473, 476, 477, 489 muricatum 477 niger 482 nigrescens  482, 484 nigrum  158, 341, 451, 453, 455, 462–6, 468, 469, 472–5, 482, 483 nigrum var. americanum  467, 472 nigrum var. humile 464 nigrum var. villosum 453 nodiflorum 472 nudum 460 opacum  463, 465 paludosum  452, 470 paniculatum  466, 485 photeinocarpum 466 platanifolium 452 pseudocapsicum 478 quadriloculatum 452 racemosum 472 rostratum  451, 452 scabrum 468 scolentum 472 seaforthianum 451 sisymbriifolium  453, 472, 477 sodomaeum 478 surattense 483 torvum  458, 459, 460, 470, 474, 483, 485 trilobatum  452, 478, 479 tuberosum  189, 220, 342, 455 valdiviense 472 variabile 466 villosum 465 virginianum 472 wrightii 451 xanthocarpum  481, 482, 483 solasodine  447, 452–6, 459–62, 465, 470, 471, 473, 476, 479, 481, 482,

489 solasonine  454, 455, 459, 462, 465, 473, 476, 478, 482–4 solatriose 460 Solenostemon scutellarioides 99 Solidago arguta 180 canadensis 180 Sonchus arvensis 446 Sophora chrysophylla 416 japonica 128 secundiflora 416 tonkinensis 446 Sparassis crispa 474 sparteine  220, 417 spathulenol  70, 300, 313, 318, 328 Spearmint  145, 178 Sphagneticola trilobata  57, 60, 62 Spiderflower  117 Yellow 114 Spilanthes acmella  52, 53, 55–8 acmella var. oleracea 56 alba 56 americana 56 calva 56–8 ciliata 57 grandiflora 52 mauritiana  52, 55, 56, 58 ocymifolia 56 oleracea  52, 53, 55–7 paniculata  53, 56, 58 uliginosa 55 spilanthol  52, 53, 56–8 Spinach  86, 122, 241, 344, 464 Spinacia oleracea 344 Spinifex Hard 269 Lobed 269 Soft 269 Spinifex triodia 268 spiroethers 69 Spodoptera littoralis 99 litura 164 spongolite 253 Squill  26, 27 St Anthony’s fire  73 St John’s Wort  186 St Mary’s Thistle 158 Staphyloccoccus aureus 29, 36, 54–75, 80, 91, 97, 101, 103, 109, 121, 124, 148, 155, 171, 172, 179, 191, 192, 194, 202, 204–7, 298, 321, 322, 334, 337, 471 aureus haemolyticus 191 epidermidis  56, 471, 321 Star Anise 42 stearic acid  34, 118 Stellaria spp. 189 Stemodia grossa 135 lythrifolia 420 viscosa 88 Stemphylium solani 103 Stenochilus glaber 297 Stephania tetrandra 148 Sticky Nightshade  453, 470 stigmasterol  56, 65, 142, 150, 435, 443, 445, 448, 479, 480 Stink Bug  337 Stinking Nightshade  463

Stinking Roger  86, 87, 88, 189 Stramonium  19, 340, 349, 351–3, 357, 358, 384 Strawberry, Mock  474, 475 Streptococcus aureus  75, 205 faecalis 459 haemolyticus 56 mutans  54, 104, 205 pneumoniae  75, 174, 321, 322 pyogenes  322, 334, 471 sanguinis  205, 282 sobrinus 104 Streptoglossa bubakii 88 decurrens 88 odora 88 streptokinase 288 Streptomyces aureofaciens 198 caespitosus 201 chrysomallus 200 coerulorubidus 201 erythreus 199 griseus 198 mediterranei 200 nodosus 200 parvullus 200 peucetius 201 rufocromogenes 201 venezuelae 197 verticillus  201 streptomycin  174, 185, 198, 445, 460, 471 strophanthin  25, 449 Strophanthus gratus  25, 449 kombe  26, 485 Strychnos toxifera 362 Succory 73 Sugarwood  308, 309 sulphur 47 Summer Adonis 25 Sunflower, Beach  53, 56, 59–61, 156 Sunflower Daisy  59, 61 Swainsona 418 swainsonine 418 Sweet Flag 151 Sweetbriar 29 Sweetweed 319 Symonanthus aromaticus 398 Symphytum 51 officinale 120 officinalis 51 Syncerus caffer caffer 262 Syzygium  189, 420 aromaticum  36, 37, 43, 319 australe 135 jambos 178 luehmannii 135 smithii 91 T tabacine 412 tabacinine 412 Tacca chantrieri 446 cheancer 446 leontopetaloides 446 plantaginea 446 subflaellaea 446 Taenia saginata 280 solium 280

551 Tagetes erecta  39, 83–87 filifolia  83, 87 glandulifera 87 lucida  83, 84, 87 minuta  83–7, 189 patula  82–7, 141   rupestris 87 subulata 87 tagetone  85, 87 Tai-fung-tze 163 Tamarillo 452 Tamarix gallica 158 Tanacetum ligulatum 320 Tangerine 75 tapeworm  29, 183, 280, 281 Taraktogeno kurzii  163, 165 Taraxacum albidum 75 aristum 70 coreanum  75, 76 cygnorum 70 formosanum 75 hepaticolor 70 japonicum  75, 76 khatoonae 70 kok-saghyz  70, 77 mongolicum  70, 74, 75, 76 officinale  64, 70, 74, 76, 158, 189 platycarpum  70, 74, 76 sinicum 74 squamulosum 70 taraxasterol 76 taraxerol 76 taraxinic acid 76 Tarragon, Mexican  84 Tasmannia lanceolata 135 Taxus baccata 10 brevifolia 447 canadensis 178 tellimagrandin I 36 teloidine 398 Tephroli 64 Tephrosia purpurea 64 Teredo novalis 267 teriloside 300 termilone 38 Terminalia arjuna 158 belerica 151 chebula  37, 64, 151 ferdinandiana 135 terminolic acid  143 termite  244, 262, 265–9, 275, 300–5, 328, 339 Cathedral 302 Harvester 304 Magnetic  302, 304 Termitomyces albuminosus 305 clypeatus 306 eurirrhizus 306 heimii 306 microcarpus 306 mummiformis 306 reticulatus 305 terpineol 43  4-terpineol 320 terpinolene  85, 320 terpinyl acetate  43, 316 Terra Sigillata  211, 212, 213, 253, 254, 255, 286

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

testosterone  102, 434 tetracycline  36, 195, 198, 227, 228, 238 tetramethylputrescine 398 tetrandrine 148 Tetranychus urticae  99, 135 tetraphyllin 165 Teucrium argutum 100 chamaedrys 178 thalictrine 112 Thalictrum foliolosum 112 thankunic acid 143 thankuniside 143 THC  191, 192 thebaine 22 thiamin 274 Thornapple Common 350 Desert 349 Downy 350 Fierce 350 Hairy 350 Native  349, 350 Oak-leaf 349 Thottea grandiflora 202 Thyme  29, 67, 144, 145, 150, 173 Mexican 100 thymol  101, 104, 108, 109 Thymus vulgaris 145 Tick, Australian Paralysis  412 Tickweed  114, 115, 116, 117 tigloidine  396, 398 tigogenin  447, 449 Tinea capitis 415 Tinospora cordifolia 151 smilacina 135 tiotropium bromide 360 Tobacco  381, 405, 407, 409, 410, 412–6, 418–20, 423, 456, 489 Australian 404 Latakia 411 Native  372, 379, 402–4, 431 Persian 410 Shiraz 411 Turkish  84, 410, 411 Velvet 409 Wild  106, 403, 406, 411, 420, 425–7 Woodland 409 tocopherol  31, 32 tokorogenin 435 tomatidenol 455 tomatidine  454, 455, 461, 479 Tomato  86, 116, 221, 291, 455, 485 Toredo navalis 419 tormentic acid 35 Torreya nucifera 328 Toxocara canis  275, 276 cati 275 Toxoplasma gondii  283, 284 trans,trans-arnesol 70 trans-anethole 44 trans-caryophyllene 104 trans-humulone 333 trans-nerolidol 44 trans-tiliroside 38 trans-β-farnesene 142 Traveller’s Joy  110, 111 trematodes  280, 282 tremolite  226, 236

Treponema pallidum pallidum 472 pallidum pertenue 472 Trichilia roka 113 rubescens 223 Trichinella spiralis 281 Trichodesma zeylanicum 420 Trichophyton mentagrophytes  55, 56, 97 rubrum  56, 97, 103, 335 Trichosanthes kirilowii 75 Trichosurus vulpecula  176, 204 Trichuris suis  280, 281 trichiura 280 vulpis 276 tricosane 30 Trigonella foenum-graecum 448, 450 trihydroxybenzaldehyde (TBA) 37 Trillium spp. 448 Triodia basedowii 269 pungens  268, 269 Triphala 151 Trisetum flavescens 489 triterpene  81, 318, 398 tropisetron 359 troxerutin 128 Trypanosoma brucei  282, 382 cruzi  54, 57, 483 tubocurarine 362 Turkey Berry 458 Turmeric  156, 158, 159, 443 Turpentine Tree  370 Tuvaraka 163 U ulcer Bairnsdale 203 Buruli 203 Daintree 203 umbelliferone  67, 69 undecanal 101 Upright Virgin’s Bower  111 Urginea maritima 26 scilla 27 urokinase 288 ursolic acid  35, 37, 144, 190, 398, 422 Urtica 47 V Vaccinium myrtillus 385 Valeriana officinalis 179 wallichii 151 valtropine 390 vancomycin  321, 324, 445 vanillin 43 Vanillosmopsis erythropappa 67 Varanus gouldii flavirufus 256 Varroa destructor 58 Velvet Nightshade 461 Velvet Tobacco 409 veratridine 485 veratrine 485 Veratrum  485, 486, 487 album  486, 487 nigrum 486 verbascoside  313, 315, 325, 326, 328

Verbascum thapsus 81 verbenone 327 vermiculite 205 Vernonia kotschyana 474 Verticordia brownii 95 plumosa 95 verticordina 95 V-Gel 39 Viannia braziliensis 54 Vibrio cholera 217 cholerae  84, 148 mimicus  56, 148 parahaemolyticus  56, 148 Vigna spp. 189 vincristine  10, 149, 171, 341 violaxanthin 142 Virgin’s Bower  112 viridiflorene  300 viridiflorol  45, 82, 300 virus, Ross River  203 Vitex agnus-castus 297 negundo  39, 98 negundo var. cannabinifolia 98 trifoliata 98 vitexin 28 voleon U 101 Vombatus ursinus 285 Vomit-wort 429 W Wallaby Agile 285 Bennett’s 285 Wasp, mud  268 Waterbush  294, 380 wattle 373 Wattle 256 Umbrella 182 Wedelia asperrima  59, 61, 66 biflora  53, 56, 58, 60, 156 calendulacea  57, 63, 64 chinensis  56, 57, 58, 63, 65, 66 glauca  58, 61 longipes 59 paludosa 54–57 parviceps 57 spilanthoides  59, 60 stirlingii 60 subvaginata 57 trilobata  54–7, 60, 62 urticifolia 60 verbesinoides 60 wedelolactone 63–66 wedeloside  61, 66 wedelosin 57 Weevil, Cotton Boll  58 whipworm 271 Canine 276 Human  280, 281 pig 280 White Hellebore  486, 487 White Nightshade  474, 483 White Star Pratia 430 Whiteroot  429, 430, 431 Whitewood, Desert  306, 307 Wild Tobacco  106, 403–6, 411, 420, 425, 426, 457 Wild Tomato 420 Wild Yam 432–4 wilgi 267

Winter Adonis  19, 25, 26 Witchetty Grub  257 Withania somnifera  151, 158 Wolf Apple 478 Wolfsbane  10, 212 Wollastonia biflora 60 Wombat, Common 285 Woodbridge Poison 427 Woodland Tobacco  409 Woody Nightshade  470, 472 Woolly Nightshade  465 Woolly Rattlepod  92 worm American boll  337 Asian armyworm  164 Canine hookworm 276 Canine roundworm  276 Canine whipworm  276 Egyptian cotton leafworm  99 filarial  53, 153, 280, 282, 454, 477 flatworm  279, 280 giant intestinal roundworm  280 hookworm  14, 275, 276 human hookworm 280 human whipworm  280, 281 meadow eelworm  87 pig whipworm 280 pinworm 280 rat tapeworm  87, 281 roundworm  14, 165, 275, 279, 337 scalp ringworm  415 silkworm 284 tapeworm 280 threadworm 280 whipworm  271, 280 Wuchereria bancrofti 280 X xanthine 130 xanthine oxidase 130 Xie Bai  174 Xylosma terrae-reginae 135 Y Ya Dan Zi  172 Yam Air-Potato  436, 444, 445 Bitter  438, 439 Japanese  435, 437 Long  444, 445 Mexican  432, 433 Wild 432–4 yamogenin  448, 454 Yellow Jessamine  147 Yew, Pacific 447 yonogenin 435 Yucca brevifolia 449 Z zeaxanthin  33, 85 zeolite  205, 238–40, 242, 253 Zi Cao 146 Zingiber officinale 44 zingiberene 44 zingiberol 44 zizaene 327 zucchini 86

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