Ginsenoside Rg1 Suppresses Hepatic Glucose Production via AMP-Activated Protein Kinase in HepG2 Cells

Panax ginseng is known to have anti-diabetic activity, but the active ingredients are not yet fully identified. In this study, we found the inhibitory effect of Rg(1) on hepatic glucose production through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Rg(1) significantly inhibited hepatic glucose production in a concentration-dependent manner, and this effect was reversed in the presence of compound C, a selective AMPK inhibitor. In addition, Rg(1) markedly induced the phosphorylations of liver kinase B1 (LKB1), AMPK and forkhead box class O1 (FoxO1), a key transcription factor for gluconeogenic enzymes, in time- and concentration-dependent manners. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities were inhibited by 24% and 21%, respectively, when the cells were exposed to 40 mu M of Rg(1) resulting from phosphorylation of FoxO1 and inhibition of gluconeogenic gene expression. Taken together, our results demonstrated the suppressive effect of Rg(1) on hepatic glucose production via LKB1-AMPK-FoxO1 pathway in HepG2 human hepatoma cells.