Comparative study of herbal medicine with allopathic medicine for the treatment of hyperuricemia

Journal of Pharmacognosy and Phytotherapy Vol. 2(6) pp. 86-90, October 2010 Available online at http://www.academicjournals.org/jpp ISSN 2141-2502 ©2010 Academic Journals

Full Length Research Paper

Comparative study of herbal medicine with allopathic medicine for the treatment of hyperuricemia M. Akram1, E. Mohiuddin2, Abdul Hannan3 and Khan Usmanghani3* 1

Department of Basic Medical Sciences, Faculty of Eastern Medicine, Hamdard University, Karachi, Madinat-al-Hikmah, Muhammad Bin Qasim Avenue, Karachi, Pakistan. 2 Department of Surgery and Allied Sciences, Faculty of Eastern Medicine, Hamdard University, Karachi, Madinat-alHikmah, Muhammad Bin Qasim Avenue, Karachi, Pakistan. 3 Department of Pre-clinical Sciences, Faculty of Eastern Medicine, Hamdard University, Karachi, Madinat-al-Hikmah, Muhammad Bin Qasim Avenue, Karachi, Pakistan. Accepted 20 August, 2010

To study the therapeutic effect of herbal medicine in comparison with allopathic medicine for treatment of hyperuricemia. One hundred patients with hyperuricemia were randomly assigned into two groups, 50 in each group. Test group was treated with herbal medicine and control group was treated with allopathic medicine; allopurinol. The hypouricemic effect was observed and the level of serum uric acid was measured before and after treatment. Comparison of data recorded by participants relating to these variables showed significant differences between test and control groups (p < 0.05). The efficacy of the test treated medication (Gouticin) was superior as p = 0.03. Gouticin is more effective than the allopurinol in the treatment of hyperuricemia. Key words: Hyperuricemia, herbal medicine, allopurinol. INTRODUCTION Uric acid is the final product of purine metabolism in human beings. The condition of hyperuricemia is indicative of a high level of uric acid in the blood (>7 mg/dl for men, >6 mg/dl for women) (Shiraishi and Une, 2009). It is cited in the literature that uric acid level is high in human subjects because of deficiency of hepatic enzyme uricase, which converts uric acid into allontoin. Approximately two thirds of total body urate is produced endogenously, while the remaining (one third) is accounted for by dietary purines. The kidneys excrete approximately 70% of the urate produced daily, while the intestines eliminate the rest (Miao et al., 2008; Brule et al., 1992). Hyperuricemia may occur as a result of underexcretion, increased production of uric acid or a combination of the two mechanisms. Underexcretion accounts for the

*Correspondence author. E-mail: [email protected]. Tel: 92-021-6440083. Fax: 92-021-6440079.

majority of cases of hyperuricemia. Overproduction accounts for only a minority of patients presenting with hyperuricemia. The prevalence rate of asymptomatic hyperuricemia in the general population is estimated at 2 - 13% (Freedman et al., 1995; Murray et al., 1991). The hyperuricemia may indicate an increased risk of gout, the relationship between hyperuricemia and gout is unclear. Many patients with hyperuricemia do not develop gout, while some patients with repeated gout attacks have normal or low blood uric acid levels. Among the male population in the United States, approximately 10% have hyperuricemia. However, only a small portion of those with hyperuricemia will actually develop gout (Gibson et al, 1984; Emmerson et al., 1992; Inai et al., 1999). The most common causes of hyperuricemia are diet, alcohol consumption, and physical activity excesses, and obesity is a strongly associated factor. Hyperuricemic therapy consists of recommendations for a diet low in purines, hydration, alkalinization of urine, and the use of drugs that increase excretion or decrease uric acid production

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(Mayes, 1993). MATERIALS AND METHODS

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criteria the patient fulfilling the hyperuricemic criteria as candidates were selected. The study period include was from 2007 - 2009. Among this population all the patient suffering from hyperuricemia were interviewed immediately and upon their consent to participate they were grouped as test and control groups.

Study design This case controlled examination based study was conducted at Shifa-ul-Mulk Memorial Hospital for Eastern Medicine on the patient living in the rural areas of 27 - 70 villages surrounding Madinat-ulHikmah Hamdard University, Karachi. The study has been conducted according to the principles of good clinical practice that is, an informed consent was obtained from the patients before enrollment and proper history and clinical examination were recorded on each follow up. The study was carried out in the period 2007 - 2009. Study period was of 18 weeks with a window for the follow up visit of 6 weeks accounting for variable duration of hyperuricemia treatment. Chi-square test and exact fisher test were used to analyze the statistical difference. Patients

Data collection Data collected for this research work included filling of clinical trial proforma through personal interview, personal observation, use of case record, file and documents. The designed clinical trial proforma specifies the clinical feature and information to be filled by the Physician for record and utilized in statistical assessment (Figure 1). Statistical analysis Statistical analysis were performed using SPSS and excel software, the Chi Square Test was determined. All differences were considered statistically significant by generating a ‘p-value’ from test statistics. The significant result with ‘p-value’ less than 0.05 was considered as statistically significant.

The study was carried out on the patients of ages between 35 - 70 years. The trial was conducted on 100 patients irrespective of socio economic status at outpatient department in Shifaul-Mulk-Memorial Hospital. The patients were divided in control and test group. Controlled group received Allopurinol (300 mg one time per day orally from Sigma Chemical Co. St. Louis, MO) and the test group received herbal medicine Gouticin Tab. 500 mg (three times per day orally). Gouticin is an herbal coded formulation of compound drugs with their synergistic action of herbal drugs design and calculated according to herbal pharmacopoeia, monographs of Unani medicine on scientific basis. Each 500 mg Gouticin tablet contains Apium graveolens 100 mg, Colchicum autumnale 50 mg, Withania somnifera 75 mg, Smilax chinensis 75 mg, Tribulus terrestris 100 mg, Zingiber officinale 100 mg. The Gouticin as such comprises of six different types of botanical drugs the quantity of which were considered on the basis of ethnomedical information as well as pointed out in Hamdard Pharmacopoeia and Tibbi Pharmacopoeia (Said, 1969). Furthermore Allopurinol 300 mg/day is the recommended dosage form as given in Pharma guide. The patients suffering from diabetes, hypertension, renal impairment and other musculoskeletal disorders were excluded from this study. As such it was monitored that patients were not suffering from any other serious disease or ailment. The literature search very clearly displayed that Allopurinol is not involved in any way with the food interaction such as vegetables and meat (chicken and fish). The patients were also directed not to consume red meat of any sort.

1. Patient with concurrent physical illness example uncontrolled hypertension and diabetes. 2. Patient with hepatic or renal impairment. 3. Patient belonging to area outside Karachi because of inherent difficulty in follow up.

Setting

Patient characteristics

The therapeutic evaluations of these medicines were conducted after the diagnoses of hyperuricemia on clinical and biochemical evaluation at Shifa-ul-Mulk Memorial Hospital, for Eastern Medicine, Hamdard University. The patients were registered from the general O.P.D. and hospitalized to the clinical Research ward of the Hospital. All the patients selected for the study, were thoroughly examined and clinical history was recorded.

The mean age of 50 patients (both male and female) in test group was 54.92 with standard deviation 10.91 as shown in Table 1. The mean age of 50 patients (both male and female) in control group was 55.66 with standard deviation 10.39 as shown in Table 1. The age distribution of patients was classified in different class interval ranging from 35 years to 70 years. The age distribution of 100 patients recorded having 7 class intervals accordingly, 35 - 40, 40 - 45, 45 - 50, 50 - 55, 55 - 60, 60 - 65 and 65 - 70 as shown in Table 2. In addition, the age group was then subjected to the treatment as test (Gouticin) and control (Allopurinol) and these randomly spread then age wise increment showed that patients of over age 50 are suffering from hyperuricemia and require treatment accordingly.

Sample selection The sample was selected from the out patient department registered and enrolled in Shifa ul Mulk Memorial Hospital and on the basis of serum uric acid level and inclusion and exclusion

Inclusion criteria The cases suffering from hyperuricemia were selected on the following lines 1. The patients suffering from hyperuricemia with serum uric acid >8 mg/dL 2. Patients between age group of 35 - 70 years. 3. Patient having no obvious pathological findings on routine examination. 4. Patients living in Karachi, Pakistan. 5. All socio-economical classes including lower, middle and upper. Exclusion criteria The cases suffering from hyperuricemia were excluded on the following lines.

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Clinical Trial Protocol for Hyperuricemia Patient ID

Date

Patient Name

F/H Name

Contact No

Age

Height

Marital Status

Religion

NIC No

Presenting Complaints

Family History

Drug History

Sex

General Physical Examination Cynosis

Anemia

Koilonychia

Clubbing

Vitals Temperature

Blood Pressure

Pulse Rate

Respiratory Rate

Sign and symptoms Pain in Joints

Pain on Joint movement

Stiffness of Joints(P/A)

Tenderness of joint

Joint Swelling

Redness of Joint

Investigations Visit Date

Hb Gm%

TLC

ESR

Platelet

Uric acid

R.A factor

C. Reactive Protein

F/RBS

Billirubin

S.G.P.T

Alk. Phosphatase

X-Ray of affected joint(Report)

Urea

Synovial Fluids

Creatinine

Diagnosis Differential Diagnosis

Provisional Diagnosis

Final Diagnosis Treatment

Gouticin Test Drug Prognosis Patient Consent

Allopurinol (Control Drug) Side effects observed Physician Name

Figure 1. Clinical trial protocol for hyperuricemia.

Treatment assignment and follow-up One hundred patients consented to participate in the study. Pretreatment clinical and laboratory parameters (serum uric acid level) for the treatment groups were noted. The two treatment groups were comparable in efficacy results and side effects of the medicine administered. All subjects were clinically studied and completed

the assigned therapy during the period 2007 - 2009.

RESULTS Gouticin and Allopurinol were prescribed to 100 patients

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Table 1. Mean distribution of age.

Treatment group (Gouticin)

Sex Male Female Total

Mean 52.62 59 54.92

Number of patients 32 18 50

Standard deviation 11.41 8.83 10.91

(Allopurinol)

Male Female Total

54.5 58.12 55.66

34 16 50

11.36 7.68 10.39

Total

Male Female Total

53.59 58.59 55.29

66 34 100

11.34 8.19 10.61

Table 2. Distribution of age.

Age group (Years) 35 – 40 40 – 45 45 – 50 50 – 55 55 – 60 60 – 65 65 – 70 Total

Treatment group Test (n) Control (n) 4 7 8 4 7 6 7 6 7 8 9 10 8 9 50 50

with serum uric acid level >8 mg/dl. This was 18 weeks study and every 6 weeks serum uric acid level was measured. Gouticin was prescribed to 50 patients with mean serum uric level 10.03 mg/dl at base line. Mean serum uric acid level of 50 patients prescribed Gouticin was 4.74 mg/dl at end of therapy. Allopurinol was prescribed for 50 patients with mean serum uric level 10.18 mg/dl at base line. Mean serum uric acid level of 50 patients prescribed Allopurinol was 5.27 mg/dl at end of therapy. DISCUSSION Allopurinol acts through inhibition of xanthine oxidase which is highly effective to treat hyperuricemia. Xanthine oxidase is responsible for the production of uric acid. Although these drugs are commonly used for treatment of hyperuricemia in patient with chronic gout. Allopurinol exerts serious side effects like skin rashes. In order to overcome this problem, there is a great need to find new medicinal agents which have good efficacy and less adverse effects. The different medicinal herbs used in this study were selected on the basis of their traditional use in Unani system of medicine. For example Colchicum autumnale and Smilax chinensis are used to treat gouty

Total (n) 11 12 13 13 15 19 17 100

conditions but in addition supplementary herbal drug such as Withania somnifera is utilized in immunity, Tribulus terrestris is involved in excretion of uric acid, Zingiber officinalis is xanthine oxidase inhibitor and Apium graveolens is also xanthine oxidase inhibitor and uricosuric (Tsi and Tan, 1997; Chopra, 1956). This unicenter trial has been conducted, for comparing the efficacy and safety of two different treatment modalities showed the greater efficacy of coded herbal formulation Gouticin as test drug and allopathic treatment Allopurinol administered as control drug for the treatment of hyperuricemia. A comparative study was conducted for herbal coded formulation Gouticin with allopathic medicine Allopurinol. Altogether 100 patients who had fullfilled the exclusion and inclusion criteria were administered the test and control drug and similarly were monitored for follow up. The patients’ gender, age and baseline clinical features at the time of enrolment were recorded in both groups. Half of the patients were treated with coded herbal formulation Gouticin and remaining half with Allopurinol administered orally. The hypouricemic effect was evaluated in both groups who took the drug as part of their regular treatment. Levels of serum uric acid, urea, and creatinine before, during, and after the treatment were measured, as well as creatinine clearance and uric

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acid clearance before and during the treatment. A hypouricemic effect was found in all the patients, regardless of age, sex. Conclusion Gouticin is more effective than the Allopurinol in the treatment of hyperuricemia as determined by p value < 0.03. Therefore control drug showed lesser efficacy than the test drug in its compliance to treat hyperuricemia. The control drug exhibited side effects like skin rashes, gastrointestinal intolerance nausea and vomiting, where the test drug did not display or show any untoward manifestation associated with the use of this medication and found acceptability by all treated patients. REFERENCES Brule DS, Savoie G (1992) Changes in serum uric acid levels in normal human subjects fed purine-rich foods containing different amounts of adenine and hypoxanthine. J. Am. College Nutr., 11(3): 353-358. Chopra RN, Nayarand SL, Chopra IE (1956). Glossary of Indian Medicinal Plants. CSIR New Delhi. pp 174-175 . Emmerson BT, Nagel SL, Duffy DL, Martin NG (1992). Genetic control of the renal clearance of urate: a study of twins. Ann. Rheum. Dis., 51: 375-377.

Freedman DS, Willianson DF, Gunter EW, Byers T (1995). Relation of serum uric, acid to mortality and ischemic heart disease. The NHANES 1 epidemiolologic follow-up study. Am. J. Epidemiol., 141: 637-644. Gibson T, Rodgers AV, Simmonds HA, Toseland P (1984). Beer drinking and its effect on uric acid. Br. J. Rheumatol., 23: 203-209. Inai K, Tsutani H, Ueda T (1999). Pathophysiology of hyperuricemia in the hematopoietic organ diseases, Gout and Nucleic Acid Metabolism. J. Gout Nucleic Acid Metabolism., 23(2) 82-186. Mayes PA (1993). Intermediary metabolism of fructose. Am. J. Clin. Nutr., 58(5 Suppl): 754S-765S. PMID 8213607. Miao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z (2008). Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the shandong coastal cities of eastern China. J. Rheumatol., 35(9): 1859-1864. Said HM (1969). Hamdard Pharmacopoeia of Eastern Medicine. Hamdard Foundation Karachi. 12: 406. Shiraishi H, Une H (2009). The effect of the interaction between obesity and drinking on hyperuricemia in Japanese male office workers. J. Epidemiol., 19(1): 12. Tsi D, Tan BKH (1997). Cardiovascular pharmacology of 3-nbutylphthalide in spontaneously hypertensive rats. Phytother. Res., 11: 576-582. Murray WV, Watcher MP, Kasper AM, Argentieri DC, Capetola RJ, Ritchie DM. (1991). Novel 6-oxo-6-naphthylhexanoic acid derivatives with anti-inflammatory and 5-lipoxygenase inhibitory activity. Eur. J. Med. Chem., 26(2): 159-166.