Antidiabetic effect of Dodonaea viscosa aerial parts in high fat diet and low dose streptozotocin-induced type 2 diabetic rats: A mechanistic approach

Context: High fat diet (HFD) and low-dose streptozotocin (STZ) is an ideal model for type 2 diabetes mellitus (T2DM) that would closely reflect the natural history and metabolic characteristics of human T2DM and is also suitable for pharmacological screening. Objective:The present study was designed to investigate the effect of the water extract (DVW) and the polar fraction of ethanol extract (DVE-4) of Dodonaea viscosa (L). Jacq. (Sapindaceae) on biochemical parameters in type 2 diabetes induced by a standardized HFD and low dose streptozotocin (25 mg/kg) in rats. Further, to elucidate the mode of action we evaluated its effects on a battery of targets involved in glucose homeostasis (in vitro studies). Materials and methods: Different doses of DVW and DVE-4 were administered once daily for two weeks to HFD + STZ diabetic rats. Quantification of biomarker quercetin was done using HPLC. Results and discussion: Both DVW and DVE-4 dose-dependently reduced blood glucose, serum insulin, homeostatic model assessment (HOMA), lipid profiles, and significantly improved glucose tolerance and HDL-c levels. In addition, the extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different, bioassays, DVW and DVE-4 showed inhibition of PTP-1B and at a concentration of 10 mu g/mL showed 60 and 54.2% binding to PPARy, respectively. Both extract/fraction exhibited stimulation of glucose uptake by skeletal muscles. Conclusion:Taken together, these results suggest that DVW and DVE-4 inhibits HFD + STZ-induced insulin resistance, lipid abnormalities and oxidative stress indicating that these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.