Antidiabetic and Hepatorenal Protective Effects of Annona reticulata Linn. Leaf Extract Alone and in Combination With Glibenclamide in Alloxan-Induced Diabetic Rats.

The pharmacological properties of Annona reticulata Linn. (Annonaceae) leaves, as reported by some tribal tribes, were investigated in this study. The antidiabetic and liver-renal protective potentials of methanolic leaf fraction and its combination with glibenclamide were evaluated in rats having alloxan-induced diabetes at doses of 200 and 400 mg/kg body weight; demonstrated notable antidiabetic potential which was dose-dependent. Following 21 days course of treatment, methanol leaf fraction (400 mg/kg) and combination of extract (200 mg/kg) along with glibenclamide (2.5 mg/kg) exhibited fasting blood glucose levels of 5.25 ± 0.06 mmol/L and 6.02 ± 0.07 mmol/L; whereas standard drug glibenclamide (5 mg/kg) showed fasting blood glucose level of 5.91 ± 0.09 mmol/L. Furthermore, the diabetic rats in extract group (400 mg/kg dosage) and in combination group showed body weight reduction values of 14.67 and 16.5 gm; which was lower than the value obtained group of rats treated with glibenclamide alone (21.83 gm). Additionally, the extract and its combination with glibenclamide were found to have significant protective impacts on the kidney and liver (p < 0.001) and to aid in the maintenance of lipid profile even in the presence of diabetes; these effects were comparable with the outcomes obtained from standard drug. Although diabetic rats demonstrated elevated liver and kidney markers levels, the groups of mice treated with methanolic leaf extract at both 200 and 400 mg/kg dosages exhibited notable maintenance of both liver and kidney markers levels. Furthermore, combination of methanol extract and glibenclamide showed serum ALT, AST, bilirubin and creatinine, BUN values of 15.20 ± 1.58 IU/L, 10.73 ± 0.45 IU/L, 3.60 ± 0.22  μmol/L; and 0.73 ± 0.03 mg/dL, 18.13 ± 2.13 mg/dL (p < 0.001); which were markedly lower than the values obtained from diabetic control rats. Moreover, both methanolic leaf extract and standard drug glibenclamide as well as their combination exhibited beneficial effect in the maintenance of serum TC, TG, LDL, and HDL levels. Methanolic extract at 400 mg/kg dosage and the combination demonstrated serum TC, TG, LDL, and HDL values of 84.33 ± 3.00 mg/dL, 62.32 ± 3.13 mg/dL, 42.67 ± 3.01 mg/dL, 37.43 ± 6.47 mg/dL; and 80.43 ± 3.53 mg/dL, 65.20 ± 6.29 mg/dL, 44.50 ± 2.88 mg/dL, 43.52 ± 3.33 mg/dL (p < 0.001), respectively. Additionally, the extract's potential components that may have played crucial roles in achieving these bioactivities were identified using the reports from the GC-MS analysis.