Antidiabetic Activity of Ethanolic Leaf Extract of Neem (Azadirachta indica A. Juss) in Streptozotocin-Induced Diabetic Wistar Rats

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The need to develop antidiabetic phytotherapies with evidence-based efficacy, dosage and safety is on the rise. Therefore, this work was designed to study the effects of Azadirachta indica (neem) treatment on the following parameters in diabetic Wistar rats: (i) diabetic hyperglycaemia; (ii) microscopic anatomy of the pancreas, liver, kidney and jejunum; (iii) plasma insulin and lipid profile; (iv) biomarkers of pancreatic and hepatic oxidative stress; and (v) biomarkers of hepatic and renal function. The study was performed on one hundred male Wistar rats, 10 weeks old, and 175.5 g body weight. Animals were randomly assigned to one of the following groups of 18 animals each: control, diabetic, diabetic + neem leaf extract, diabetic + metformin, and neem leaf extract only. Hyperglycemia was induced with an intraperitoneal dose of streptozotocin (70 mg/kg body weight). Ethanolic leaf extract of neem was administered orally at 500 mg/kg body weight/day and metformin at 350 mg/kg body weight/day for 50 days. In each group, six animals were sacrificed on days 7, 21 and 50, under pentobarbital anaesthesia. Blood glucose was estimated, feed and water intake was monitored, and body and organ weights were taken. Plasma was analysed for insulin, lipids, and markers of hepatic and renal function. Oxidative stress biomarkers were assayed in pancreas and liver homogenates; while the liver, kidney, pancreas and jejunum were processed for histologic studies. At 50 days, light microscopic study of the pancreas, liver and kidney of untreated diabetic rats showed deteriorated islets of Langerhans, hepatic glycogenosis (glycogen storage disease of the liver) and diabetic nephropathy, respectively. In the jejunum, epithelial erosion and necrosis of goblet cells were observed in these untreated diabetic Wistar rats. Treatment of diabetic rats with the leaf extract of neem and metformin ameliorated hyperglycemia and prevented organ complications. However, hepatic sections of neem-treated and metformin-treated diabetic rats showed mild lobular inflammation and hepatocyte vacuolation, respectively (at day 50). Besides, hepatic oxidative stress was exacerbated in neem-treated diabetic rats; while pancreatic oxidative stress was ameliorated in the same group. Moreover, plasma insulin, lipids, liver enzymes (except alkaline phosphatase), urea and creatinine were not significantly different from control in the neem-treated diabetic rats at day 50 (P>0.05). Thus, findings from this study show that the ethanolic leaf extract of A. indica is beneficial against the following biochemical and anatomic perturbations in streptozotocin-induced diabetic Wistar rats: (i) diabetic hyperglycaemia; (ii) hepatic glycogenosis; (iii) diabetic nephropathy; and (iv) pancreatic islet lesions. Furthermore, this extract improves plasma insulin, prevents streptozotocin-induced intestinal mucosal lesions and ameliorates diabetic dyslipidaemia. The last effect suggests that the extract may reduce the morbidity and mortality associated with increased cardiovascular events characteristic of diabetic dyslipidaemia. However, the increased hepatic lipid peroxidation observed in these neem-treated diabetic rats suggests association of hepatic oxidative stress with chronic A. indica treatment.



Diabetes Neem Streptozotocin Azadirachta indica Rats