Increasing the Level of IRS-1 and Insulin Pathway Sensitivity by Natural Product Carainterol A

Carainterol A is a eudesmane sesquiterpenoid extracted from Caragana intermedia. We have reported that carainterol A showed potent glucose consumption activity in C(2)C(12) muscle cells and the db/db mouse model. However, the mechanism of the hypoglycemic effect of carainterol A remains elusive. In this article, we present a network pharmacology approach to predict the target and signaling pathway of carainterol A which was subsequently validated in HepG2 cells. It was demonstrated that carainterol A could increase the protein levels of IRS-1 and the downstream protein kinase AKT phosphorylation at a low micromolar level. These findings suggest that carainterol A can be a valuable lead compound and a promising chemical probe for the insulin signaling pathway.