Antidiabetic effect of Dodonaea viscosa (L). Lacq. aerial parts in high fructose-fed insulin resistant rats: a mechanism based study.

To study the effect and mode of action of water extract (DVW) and polar fraction of ethanol extract (DVE-4) of D. viscosa in high-fructose diet induced insulin resistance in male Wistar rats. D. viscosa's effects were evaluated on a battery of targets involved in glucose homeostasis (in vitro studies). Rats were rendered insulin resistant by feeding 66% (w/w) fructose and 1.1% (v/w) coconut oil mixed with normal pellet diet (NPD) for six weeks. DVW and DVE4 at different doses were administered simultaneously. At the end of the study, blood glucose, oral glucose tolerance test, lipid profile and insulin were estimated and homeostatic model assessment (HOMA) levels were calculated. In addition, enzymatic and nonenzymatic liver antioxidant levels were also estimated. Quantification of biomarker quercetin was done using HPLC. Fructose diet with DVW, DVE-4 significantly reduced blood glucose, serum insulin, HOMA, lipid profiles and significantly improved glucose tolerance and HDL-c levels. In addition, these extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different bioassays, DVW and DVE-4 inhibited protein tyrosine phosphatase-1B with IC50 65.8 and 54.9 microg/ml respectively and showed partial inhibition of dipeptidyl peptidase-IV. Moreover, DVW and DVE-4, at 10 microg/ml showed 60 and 54.2% binding to peroxisome proliferator-activated receptor-gamma. Further, 2.1% (w/w) of quercetin was quantified in bioactive-DVE-4 using HPLC method. The results provide pharmacological evidence of D. viscosa in treatment of prediabetic conditions and these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.