PHARMACOLOGICAL EFFECTS AND SAFETY PROFILE FOLLOWING ADMINISTRATION OF POLY-HERBAL EXTRACT IN DIABETIC RATS

Abstract
Diabetes mellitus describes a metabolic disorder of multiple etiology characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. It is one of refractory diseases identified by Indian Council of Medical Research for which an alternative medicine is a need for the treatment. Looking to the pharmacological properties of different plant varieties like Allium cepa, Trigonella faenum-graecum, Tinospora cordifolia, Gymnema sylvestre, Syzigium cumini and Momordica charantia, the present study was carried out to evaluate the pharmacological effects and safety profile following administration of poly-herbal extract in streptozotocin induced diabetic rats. Thirty Srague-Dawley rats were randomly divided based on body weight in five groups (C1, C2, C3, T1 and T2). Rats of four groups (C2, C3, T1 and T2) were injected with streptozotocin to induce diabetes. Rats of group C1, C2, and C3 were kept as normal, diabetic and standard control, respectively. Rats of group C3 were administrated with glibenclamide (5 mg/kg, PO for 28 days). Rats of group T1 and T2 were treated with mixture of polyherbal extract at 100 and 200 mg/kg, respectively orally for 28 days. After induction of diabetes, clinical symptoms of diabetes were observed in rats of diabetic control group. These symptoms were mild to moderate in all other treatment groups compare to diabetic control group. Administration of poly-herbal extract significantly (P<0.05) reduced the blood glucose level in T1 and T2 experimental groups especially at 4th week of experiment. However the blood glucose level was maximally reduced in glibenclamide treated group. In oral glucose tolerance test (OGTT), the blood glucose levels in rats of different treatment groups were significantly (P<0.05) increased at 30 and 60 minutes after oral glucose administration at dose of 2 g/kg. The little higher blood glucose levels in group T1 and T2 indicates inability of poly-herbal extract to reduce the increased blood glucose level at day 15. This result was supported by no effect of poly-herbal extract treatment on regulation of blood glucose level up to 3 weeks of our study period. In lipid profile, levels of total cholesterol, triglyceride and LDL-cholesterol were non-significantly (P>0.05) increased while levels of HDL-cholesterol were significantly (P<0.05) lower in diabetic control group compared to other groups. The mean levels of total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol in rats treated with poly-herbal extract were found comparable to normal control rats. In hematological parameters, mean values of PCV and TEC in rats of diabetic control were significantly (P<0.05) lower compared to other groups. Whereas, the mean value of above parameters in rats treated with poly-herbal extract was significantly (P<0.05) higher than other treatment groups. In biochemical parameters, mean values of ALT, AST, BUN and creatinine were non-significantly increased while, the mean values of total protein, albumin, globulin and total bilirubin were found non-significant in all groups compared to control rats. In case of antioxidant parameters evaluated from blood, liver, kidney and pancreas tissue samples, mean values of SOD, catalase and GSH in diabetic control group were non-significantly (P>0.05) decreased compared to control group. Whereas, the mean values of SOD, catalase and GSH were non-significantly (P>0.05) higher in glibenclamide as well as in poly-herbal treated groups compared to diabetic control group at the end of study period. Upon gross examination of pancreas, no appreciable gross lesions in all treatment groups have been observed. Macroscopic examination of liver and kidneys of experimental rats of diabetic control group shown congestion, paleness and mild to moderate enlargement. No appreciable macroscopic lesions have been observed in the spleen, heart and lung of rats in all treatment groups. The histopathological changes of pancreas of rats of diabetic control group (C2) revealed varying degree of structural changes as well as degenerative changes, vascular changes and infiltration of inflammatory cells with loss of normal architecture of parenchyma and changes in kidney were also observed in rats of diabetic control group. No appreciable histopathological lesions have been observed in the liver, spleen, heart and lung of rats in all treatment groups. In conclusion, administration of poly-herbal extract at the dose rate of 200 mg/kg, PO for 28 days have shown ameliorating effect on glucose, lipid profile and antioxidant levels and pathological lesions in diabetic rats. Though the findings of this short term study are encouraging, further detailed investigation is required to determine the effect of long term administration of poly-herbal extract in diabetic rats
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