Abstract
Abstract Diabetes is a metabolic disorder marked by hyperglycemia and affects millions of individuals. The adverse effects of antidiabetic drugs highlight the demand for natural therapies. Medicinal plants have been used in traditional medicine and contain bioactive compounds such as polyphenols with hypoglycemic properties. The main objectives of this study were to assess the phenolic composition of the ethanolic extracts of Lepidium sativum L. seeds (Ls) and Annona squamosa L. leaves (As) and to investigate the antidiabetic potential of the combined extracts on streptozotocin (STZ) induced diabetic male rats. Forty-eight rats were assigned equally to a normal control group, a diabetic control group, and six diabetic treatment groups, which received either individual plant extracts at 200 or 400 mg/kg bw/day or combined extracts at 100 or 200 mg each/kg bw/day for 3 weeks. The effects of the freeze-dried extracts on fasting blood glucose (FBG), plasma insulin, rat fructosamine, albumin, creatinine, lipid profile and histopathological changes of the pancreas, kidney and liver were evaluated. Additionally, area-under-the-curve values for oral glucose tolerance and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated for all experimental groups. Results indicated that Ls seed extract at 400 mg/kg bw/day or combined extracts (Ls + As) at 200 mg each/kg bw/day decreased FBG, HOMA-IR values, glucose intolerance and serum creatinine in STZ-treated animals to near normal levels. Histopathological analysis displayed moderate degrees of improvement in the pancreatic, kidney and hepatic tissues of diabetic rats treated with the combined extracts (Ls + As) at 200 mg each/kg bw/day. These results demonstrated that the combination of Ls and As extracts exerted enhanced antidiabetic effects compared to the single-extract by regenerating β-cells and increasing insulin expression. This improvement could be attributed to synergistic effects of bioactive polyphenolic constituents present in the extracts of Ls seeds and As leaves, such as ρ-coumaric acid, rutin, naringenin and myricetin. Graphical Abstract