Hypoglycemic activity of 6-bromoembelin and vilangin in high-fat diet fed-streptozotocin-induced type 2 diabetic rats and molecular docking studies

Aims: This paper investigates the hypoglycemic activity of two derivatives of embelin (1) viz. 6-bromoembelin (2) and vilangin (3), in high-fat diet - STZ induced diabetic rats. Main methods: The effects of 6-bromoembelin (2) and vilangin (3) on insulin resistance, beta-cell dysfunction and glucose transport in high-fat diet (HFD) fed-streptozotocin (STZ) (40 mg/kg) induced type 2 diabetic rats were evaluated. The binding modes of 6-bromoembelin (2) and vilangin (3) into PPAR., PI3K, Akt, and GLUT4 were also studied using Autodock 4.2 and ADT 1.5.6 programs. Key findings: At the dose of 30mg/kg, the plasma glucose, plasma insulin and body weightwere reduced by both embelin derivatives in diabetic rats. Additionally the altered lipid profiles and hexokinase, glucose-6-phosphatase and fructose-1,6-bisphosphatase levels were brought to normal. Compared to diabetic control group, there was a significant increase in the expression of PPAR. in epididymal adipose tissue. Inhibition of adipogenic activity and mild activation of PPAR. levels in the skeletalmuscle and liver were observed. In epididymal adipose tissue, the compounds increased the insulin-mediated glucose uptake through the activation and translocation of GLUT4 in PI3K/p-Akt signaling cascade. Significance: The derivatives of embelin such as 6-bromoembelin (2) and vilangin (3) may be useful in the prevention and treatment of obesity-linked type 2 diabetes mellitus. (C) 2016 Elsevier Inc. All rights reserved.