Biological Evaluation, Isolation, and Characterization of Novel Polyphenol Derivatives fromSchleichera oleosa (Lour) Oken as Anti-diabetic Agents

Background: The treatment of diabetes involves insulin and many different oral hypoglycemic drugs. In chronic disease conditions, medications potentially lose viability. Therefore, searching for more effective and safer natural anti-diabetic agents has continued to be an important area of investigation Objective: The present study aims to investigate the effect of ethanolic and aqueous extracts of Schleichera oleosa (S. oleosa) on diabetic rats and isolate and characterize the active compound from an effective extract. Method: The ethanolic and aqueous extracts were administered orally (200 and 400 mg/kg, for 28 days) to streptozotocin-nicotinamide-induced diabetic rats. Hypoglycemic effects, OGTT, alteration in body weight, lipid profile, biochemical parameters, hepatic enzymes, and histopathological examination were assessed. Afterwards, the active constituents of the effective extract were isolated using column chromatography, and the preliminary structural features were investigated by FTIR, 1H NMR, 13C NMR, and LC/MS. Results: The extracts treated rats showed a significant reduction in the fasting blood glucose level (FBGL), total cholesterol, triglycerides, LDL, VLDL, and stress markers (MDA, SGOT, SGPT), and a significant increase was observed in the concentrations of HDL and bodyweight when compared to the diabetic rat. Furthermore, the extract restored the altered level of antioxidant enzymes and glucose metabolizing hepatic key enzymes. Histopathological evaluation of the pancreas revealed the regeneration of the β-cells in diabetic rats, which was earlier necrosed by streptozotocin. In this study, an active constituent SMK/SO/01 was isolated from the effective ethanolic extract, and further spectral studies confirmed it as belonging to the polyphenolic category. Conclusion: These findings provide scientific evidence that SMK/SO/01 has the potential to be a potential drug candidate for diabetes mellitus and complications induced by the disease. Also, these results prove that ethanolic extract of S. oleosa leaves exerts effective anti-diabetic activity, which provides scientific backing for folklore medicine.