Taraxasterol Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis via the PI3K/Akt Signaling Pathway

Abstract

Objective: Taraxasterol (TS) is the main active compound of Taraxacum, which plays a significant role in the treatment of diabetes in many classic prescriptions. However, the mechanisms of TS in the treatment of diabetes remain unclear. This study aimed to investigate the underlying mechanism of TS in hepatic gluconeogenesis and glycogen synthesis in HepG2 cells with insulin resistance (IR). Methods: Molecular docking was conducted by using Discovery Studio (DS) to predict the target of TS in the treatment of diabetes. Then we treated HepG2 cells with glucosamine for 18 h. After the cells were treated with TS, the glucose consumption was examined. Oil red O staining was used to detect the lipid accumulation of HepG2 cells, and cellular glucose uptake levels were assessed using fluorescent 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxy-D-glucose. The expression of the related proteins of the PI3K/Akt signaling pathway in the HepG2 cells was evaluated by western blot assay. Results: The molecular docking analysis revealed a good binding pose between the insulin receptor and TS. Furthermore, TS administration significantly enhanced glucose uptake and consumption, and reduced lipid accumulation in HepG2 cells with IR. The results of pharmacological mechanism study showed that TS up-regulated glycogenesis by PI3K/Akt/GSK3-motivated GS activation, and down-regulated gluconeogenesis by PI3K/Akt/FoxO1 expression of PEPCK and G6Pase in HepG2 cells with IR. Conclusions: Molecular docking and in vitro experimental results indicate that TS suppresses hepatic gluconeogenesis and augments glycogen synthesis by the PI3K/Akt signaling pathway, and it may have similar effects as insulin in regulating blood glucose.