Isofraxidin exerts anti-diabetic, antilipidemic, and antioxidant effects and protects renal tissues via inhibition of NF-ĸB in Streptozotocin-induced diabetic rats

BackgroundDiabetes mellitus is a life-threatening metabolic disorder responsible for the death of millions of individuals from its complications. Developing new therapeutic drugs that can control DM and prevent its complication is of great significance.ObjectiveThe present study investigates the protective effect of Isofraxidin (ISO) against diabetes and its complications. Streptozotocin was used to induce diabetes in male Wistar albino rats. The effect of ISO was examined on blood glucose, plasma insulin, and other biochemical parameters depicting level of antioxidant status, and renal and lipidemic function. Western blot and docking study was also conducted to determine the mechanism of action of ISO.ResultsResults of this study suggest that ISO improved blood glucose level and plasma insulin level. It showed hypolipidemic (via reducing TC, TG, and LDL-c, and increasing HDL-c) and renal protective action (reducing BUN, SCR, and GSP) in STZ diabetic rats. It also restored the damaged architecture of kidney tissues as compared to STZ diabetic rats. The level of oxidative stress in ISO-treated rats was found reduced due to improvement in the antioxidant enzymatic system (SOD, CAT, and GSH). The expression of NF-ĸB was also found significantly downregulated in the ISO-treated group in Western blot analysis. Docking analysis showed excellent binding affinity of ISO by creating numerous H-bonds and non-bonded interaction with Lys145 of chain A and chain B, and Tyr57 of NF-ĸB.ConclusionOur study demonstrated the substantial anti-diabetic, antilipidemic, and antioxidant effects of ISO, which protects renal tissues possibly via the inhibition of NF-ĸB in Streptozotocin-induced diabetic rats.