Therapeutic evaluation of a polyherbal formulation in type 2 Diabetes mellitus

Indian Journal of Traditional Knowledge Vol. 10 (4), October 2011, pp. 711-715 Therapeutic evaluation of a polyherbal formulation in type 2 Diabetes mellitus Anas* M, Mohsin M, Siddiqui M & Mannan A Department of Moalijat, Ajmal Khan Tibbiya College, Aligarh Muslim University, Aligarh-202002, UP E-mail: anasshamsi77@yahoo.com Received 26.08.09; revised 31.12.09 After thorough review of literature, both from classical as well as modern medicine a clinical trial on a combination of herbal drugs was carried out in Diabetes mellitus. Herbal drugs are frequently used for various ailments since time immemorial without any known apparent side effects but these herbal drugs have not been scientifically evaluated so far. Keeping in mind India as a diabetic capital of the world, an attempt has been made to evaluate therapeutic efficacy of Unani formulation in the treatment of Diabetes mellitus. In this study, the formulation was given in powder form in 6 gm twice a day doses for 3 months in the diagnosed patient of Diabetes mellitus who has given written consent to participate in the study. The study was a comparative study and observations were analyzed statistically for the test of significance and results were promising. Keywords: Diabetes mellitus, Polyherbal formulation, Hyperglycaemia IPC Int. Cl. 8 : A01D 16/02 Diabetes mellitus is a disease which was recognized in antiquity but its history has been characterized by numerous cycles of discovery neglect and rediscovery. It has now reached epidemic proportion, and affects more than 170 million people world wide. Global estimate for the year 2010 predicts a further growth of almost 50%, with the greatest increase in the developing countries of Africa, Asia and South America 1. Epidemiological data in India shows the same upward trend from 33 million diabetics in 2000 to 57 million in 2025, India has thus become the Diabetic Capital of the world. Type 2 Diabetes mellitus with early age onset carries higher risk of vascular disease, 4-5 times for stroke, 5 times for nephropathy, and even higher for peripheral vascular disease 2. Earlier it was believed that diabetes occurs due to abnormality in kidney function (Sue Mizaj har of kidney) 3,4,5,6. Zia-bi-tus is a Unani word means to run through while mellitus is a Latin word means sweetened with honey 7. Review of old literature reveals that the diabetes was described on the basis of clinical triad of polyuria, polydipsia and polyphagia 8,9. Since the beginning of 19 th century, diabetes has been studied by the scholars on modern parameters and much more information about its causes, *Corresponding author pathogenesis, diagnosis have been collected. Although the precise aetiology of both types of primary diabetes, i.e. Type 1 or Insulin dependent Diabetes mellitus and Type 2 of non-insulin dependent Diabetes mellitus is uncertain, However environmental factors interact with a genetic susceptibility to determine which of those with a genetic predisposition develop the clinical syndrome, and the timing of its onset. Although Type 2 Diabetes mellitus is more common than Type 1 Diabetes mellitus and more frequently exhibit familial aggregation, its pathogenesis is less well understood. Diabetes is characterized by variable degree of insulin resistance, impaired insulin secretion and increased glucose production and the major environmental factor is obesity 10. An effort has been made to identify the genes associated with diabetes two approaches have been applied. First candidate or single gene approach and secondly genome wide scan approach. The candidate gene approach in attempts to identify a causative factor among the obvious biological candidates for insulin resistance has been largely disappointing. Further, Adipocytes secrete a number of biological products like interleukin-6, tumor necrosis factors and free fatty acid that may contribute to insulin resistance. Patients with Type 2 Diabetes mellitus have two physiologic defects, abnormal insulin secretion and resistance to insulin action,

712 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 10, No. 4, OCTOBER 2011 which one of the abnormality is primary is not known. Descriptively, three phases can be recognized. In the 1 st phase, the plasma glucose remains normal despite demonstrable insulin resistance, because insulin levels are elevated. In the 2 nd phase, insulin resistance worsens and post prandial hyperglycaemia occurs and insulin level remains high. In the 3 rd phase, insulin resistance persists and also insulin secretion decreases resulting in fasting hyperglycaemia, ultimately β-cell failure may ensue. If hyperglycaemia is not controlled it may lead to various macro and micro vascular complications and even death. Composition of formulation: (each 6 gm contain the following drugs) Traditional name Scientific name Amount Neem Melia azadirachta Linn. 11 1 part Jamun Syzygium cumini Lam. 11 1 part Kalounji Nigella sativa Linn. 12 1 part Karela Momordica charantina Linn. 12 1 part Methi Trigonella foenum graceum Linn. 13 1 part Material and methods This clinical study was carried out on 50 patients of Type 2 Diabetes mellitus in the out door and indoor sections of Ajmal Khan Tibbiya College and Hospital, Aligarh Muslim University, Aligarh, during the period extending from May 2003 to August 2005. Diagnosis was confirmed by WHO criteria. Patients who were young, in whom insulin dependence was suspected, those who had taken insulin in any form at any time, those having ketonuria, and pregnant ladies were excluded from the study. The patients were divided into two groups: 1. Comparative group, and 2. Test group Comparative group comprises of 20 patients, and were advised to take 1800 Kcal diet/day, while the test group comprises of 30 patients, in whom the test drug (Formulations are given else where) in powder form is given in the dosage of 6 gm twice a day for 3 months for oral administration. The follow up of patients were performed fortnightly, all the necessary base line investigations were carried out before starting the treatment, blood sugar and urine examinations were done monthly while lipid profile and HbA 1 C, blood urea, serum creatinine and liver function test were carried out before starting the treatment and at the end of the study. All the observations and result were statistically analyzed applying paired T test and Z test. Observations Results and discussion From the above results it is quite evident that the formulation is effective in patients with Type 2 DM as compared to comparative group. Table 1 shows base line demographics. Tables 2 & 3 are showing improvement in classical symptoms of comparative and test groups, respectively. There is an improvement in symptoms in both the groups, but the test group shows a greater percent reduction in the symptoms compared to the comparative group. The improvement in the symptoms is may be due to glycaemic control in Diabetic patients. Table 4 shows effect of test formulation as compared to comparative group on glycosuria (t =2.6; p< 0.05), this effect of test formulation is may be due to antihyperglycaemic activity of the ingredient of test formulation. Table 5 shows the effect of test drug, on random blood sugar on test group as compared to comparative group (t= 6.3; p <0.001), the reduction of blood sugar in Table 1 Base line demographics Comparative group (n = 20) Test group (n = 30) No. of patients Percentage No. of Percentage patients Male: Female 11:9 55:45 9:21 30:70 Age in yrs 30-40 3 15 8 26.6 40-50 10 50 11 36.6 50-60 7 35 11 36.6 Occupation Service 7 35 6 20 Business 5 25 5 16.6 House Wife 6 30 13 43.4 Others 2 10 6 20 Food Habits Vegetarian 8 40 10 33.3 Non Veg. 12 60 20 66.7 Temperament Sanguine 3 15 0 0 Phlegmatic 15 75 20 66.7 Bilious 2 10 10 33.3 Melancholic 0 0 0 0 Risk Factors +ve Family History 9 45 11 36.6 Stress +ve 2 10 19 63.3 No exercise 18 90 28 93.3 BMI 23Kg/m 2 11 55 13 43.3

ANAS et al.: EVALUATION OF POLYHERBAL FORMULATION IN TYPE-2 DIABETES 713 Table 2 Showing effect on classical symptoms in comparative group (n=20) Symptoms 0 Day 15 Days 30 Days 45 Days 60 Days 75 Days 90 Days Polydipsia 6 5 4 4 2 2 2 No of patients improved - 1 2 2 4 4 4 Improvement % - 16.6 33.3 33.3 66.6 66.6 66.6 Polyphagia 2 2 2 2 1 1 1 No of patients improved - 0 0 0 1 1 1 Improvement % - 0 0 0 50 50 50 Polyuria with or without Nocturia 7 6 4 3 3 2 2 No of patients improved - 1 3 4 4 5 5 Improvement % - 14.2 42.8 57.1 57.1 71.4 71.4 Weight Loss 5 5 3 3 3 3 3 No of patients improved - 0 2 2 2 2 2 Improvement % - 0 40 40 40 40 40 Weakness 11 10 8 6 5 5 4 No of patients improved - 1 3 5 6 6 7 Improvement % - 9.09 27.7 45.4 54.5 54.5 63.3 Genital Candidiasis 0 0 0 0 0 0 0 No of patients improved - - - - - - - Improvement % - - - - - - - Erectile dysfunction 0 0 0 0 0 0 0 No of patients improved - - - - - - - Improvement % - - - - - - - Paraesthesia 2 2 2 2 2 2 2 No of patients improved - 0 0 0 0 0 0 Improvement % - 0 0 0 0 0 0 comparative group is due to restricted calorie diet, it has been proved that 50% of newly diagnosed cases can be controlled by diet alone 2. As far as test group is concerned the effect is may be due to ingredient of test formulation like Momordica charantia Linn. and Azadirachta indica which posses insulin like activity 12, Trigonella foenum-graceum Linn. which inhibits intestinal absorption of glucose and decrease the rate of gastric emptying by the action of dietry fibres 13, Eugenia jambolana may increase activity of hexokinase and decreases the activity of glucose 6 phosphatase in liver, or it may check the pathological conversion of starch into sugar 13. Lipid metabolism is also disturbed in diabetes mellitus. The effect of test formulation on total cholesterol is shown in Table 6 (t=2.3, p<0.05). This effect of test formulation is may be due to ingredient of test drugs like Momordica charantia, Nigella sativa Linn. and Trigonella foenum graceum Linn. These drugs may increase excretion of faecal bile acids and neutral steroids which lower cholesterol levels in blood and other tissues or by some other unknown mechanism. Glycated haemoglobin is also performed but the result is not significant (Table 7) when it is compared to comparative group (t = 1.3,) it is may be due to short duration of study. Conclusion On the basis of this study, it could be concluded that the formulation exhibited antihyperglycaemic activity for which significant improvement in symptoms and sign were observed and significant euglycemia was attained. But to observe the effect of formulation on the level of glycated haemoglobin, which was not significant long-term studies are needed.

714 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 10, No. 4, OCTOBER 2011 Table 3 Showing effect on classical symptoms in test group (n=30) Symptoms 0 Day 15 Days 30 Days 45 Days 60 Days 75 Days 90 Days Polydipsia 17 12 4 4 4 6 6 No of patients improved - 5 13 13 13 11 11 Improvement % - 29.4 76.4 76.4 76.4 64.7 64.7 Polyphagia 14 13 9 4 2 3 3 No of patients improved - 1 5 10 12 11 11 Improvement % - 7.1 35.77 71.4 85.7 78.5 78.5 Polyuria with or without Nocturia 24 21 13 15 11 9 9 No of patients improved - 3 11 9 13 15 15 Improvement % - 12.5 45.6 37.5 54.1 62.5 62.5 Weight Loss 11 11 10 10 8 6 6 No of patients improved - 0 1 1 3 5 5 Improvement % - 0 9.09 9.09 27.2 45.45 54.54 Weakness 27 27 26 20 11 9 9 No of patients improved - 0 1 7 16 18 18 Improvement % - 0 3.7 25.9 59.2 66.6 66.6 Genital Candidiasis 5 5 3 2 2 1 1 No of patients improved - 0 2 3 3 4 4 Improvement % - 0 40 60 60 80 80 Erectile dysfunction 4 4 4 3 3 2 2 No of patients improved - 0 0 1 1 2 2 Improvement % - 0 0 25 25 50 50 Paraesthesia 6 6 6 6 6 6 6 No of patients improved - 0 0 0 0 0 0 Improvement % - 0 0 0 0 0 0 Table 4 Showing effect on glycosuria t = 2.6 p< 0.05 Comparative group (n=20) 0 Day 30 Days 60 Days 90 Days Sum 23 19.5 17.5 15.5 Mean ± S.D. 1.15 ± 0.42 0.97 ± 0.40 0.87 ± 0.44 0.78 ± 0.46 % decreased 15.2 23.9 32.6 Sum 35 27 18 12.5 Mean ± S.D. 1.17 ± 0.41 0.90 ± 0.54 0.60 ± 0.55 0.42 ± 0.51 % decreased 22 48.6 64.3 Table 5 Showing effect on random blood sugar t = 6.3, p < 0.001 0 Day 30 Day 60 Days 90 Days Comparative Blood Sugar Mean ± S.D. % of fall 259.1 ± 180.7 235.3 ± 68.6 217.4 ± 51.4 182.8 ± 23.2 group (n=20) 9.2 16.2 29.7 Test group Blood sugar mean ± S.D % of fall 282.27 ± 57.15 245.0 ± 57.84 204.1 ± 43.94 158.6 ± 53.71 (n=30) 13 27.1 43.8 Table 6 Showing effect on total cholesterol t = 2.3 p < 0.05 Total Cholesterol Comparative group (n=20) 0 Day 90 Days 0 Day 90 Days Sum 3795 3849 5877 5181 Mean ± S.D. 189.75 ± 31.3 192.45 ± 30.7 195.9 ± 32.6 172.7 ± 28.6

ANAS et al.: EVALUATION OF POLYHERBAL FORMULATION IN TYPE-2 DIABETES 715 HbA 1 C Table 7 Showing effect on glycated haemoglobin t = 1.28 not significant Comparative group (n=20) 0 Day 90 Days 0 Day 90 Days Sum 172.0 159.4 250.49 219.46 Mean ± S.D. 8.6 ± 0.62 7.97 ± 0.79 8.35 ± 0.82 7.31 ± 1.36 Acknowledgement The authors are very thankful to the Chairman, Department of Moalejat, AKTC, AMU, Aligarh for their co-operation in the study, and providing all the necessary equipments and man power, and we are also thankful to the editors of IJTK for their support. References 1 M Stumvoll, Barry J Goldstein & Timon W van Haeften, Etiopathogenesis and treatment of type 2 NIDDM, Lancet, 365 (9-15) (2005) 1333-1342. 2 Haslett C & Chilves ER, Davidsson s principles & practice of Medicine, 19 th edn, (Churchill Livingstone, New York), 2002, 644 & 656. 3 Ibn-e-Sina Al Qanoon fit-tib III part II, (Nami Press, Lucknow), 1906, 420-421. 4 Kabeeruddin M, Tarjuma-e-Kabeer III, (Daftarul Maseeh Bazar Noorul Umri, Hyderabad), 1916, 27-37. 5 Razi ABMBZ Al Hawi fit-tib, X, 1 st edn, (Dairatul Maarif Al-Usmania press, Hyderabad), 1967, 189-191. 6 Majoosi AA, Kamil-us-Sana II, (Amra Press, Egypt), 1873, 409-410. 7 Ahuja MMS Practice of diabetes mellitus in India, (Bharat Mudarana layer Naveen press, Delhi), 1983, 11. 8 Kabeeruddin M, Urdu translation Al-Akseer II, reprint, (al Shifa Gulbarg Faisalabad), 2000, 1195-197. 9 Samarqandi N, Aqsarayee II, (Munshi Naval Kishore press, Lucknow), 1907, 981. 10 Powers AC, Diabetes Mellitus in Harrison s principles of internal medicine 2, 15 th edn, edited by Braunwald E, Facci AS, Kasper DL, Hauser SL, Longo DL and Jameson JL; (McGraw Hill Companies, Inc., US), 2001, 2109 & 2114. 11 Anonymous, The Wealth of India I, (Publication and Information Directorate, New Delhi), 1948, 33-34, 140-142. 12 Anonymous, The Wealth of India VII, (Publication and Information Directorate, New Delhi), 1996, 63-65, 91-92. 13 Anonymous, The Wealth of India X, (Publication and Information Directorate, New Delhi), 1996, 100-104. 14 Grover J, Yadav S & Vats V, Medical Plants of India with Anti-Diabetic Potential, Ethnopharmacol, 81 (2002) 81. 15 Prince PSM, Menon VP, & Pari L, Antidiabetic activity of Eugenia Jambolana, Phytother Res, 2 (1997) 529-531.