Selected compounds derived from Moutan Cortex stimulated glucose uptake and glycogen synthesis via AMPK activation in human HepG2 cells

Abstract

Aim of the study: To evaluate the effect of selected compounds derived from Moutan Cortex on glucose uptake and glycogen synthesis associated with AMPK activation in insulin-resistant human HepG2 cell.

Materials and methods: The effect of isolated compounds (1-16) on glucose uptake and glycogen synthesis was performed using HepG2 cells. The western blot was used to determine the expression of AMPK and its downstream substrates, ACC, p-ACC, and p-GSK-3beta.

Results: The effects of the 16 compounds from Moutan Cortex on glucose metabolism in HepG2 cells under high glucose conditions were evaluated. Compounds 2, 3, and 6 displayed highly potent effects on the stimulation of glucose uptake and glycogen synthesis in human HepG2 cells under high glucose conditions. Compounds 2, 3, and 6 phosphorylate AMPK (AMP-activated protein kinase), and resulted in increased phosphorylation of GSK-3beta and suppression of lipogenic expression (ACC and FAS) in a dose-dependent manner. Compounds 2, 3, and 6 also demonstrated interesting, strong eNOS phosphorylation in human umbilical vein endothelial cells (HUVECs). Compounds 1, 4, 5-12, and 14 displayed considerable effects on hepatic glucose production, AMPK activation, and phosphorylation of GSK-3beta in HepG2 cells under high glucose conditions.

Conclusions: These effects may indicate that the activation of AMPK by the active compounds from Moutan Cortex has considerable potential for reversing the metabolic abnormalities associated with type-2 diabetes.