Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Biol Pharm Bull. 2010;33(2):325-8. doi: 10.1248/bpb.33.325.
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 microM 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.
人参被认为具有抗糖尿病活性，但活性成分尚未完全确定。在这项研究中，我们发现 Rg(1) 通过激活肝葡萄糖生成的 AMP 激活蛋白激酶 (AMPK) 在 HepG2 细胞中的抑制作用。Rg(1) 显著地以浓度依赖的方式抑制肝葡萄糖生成，并且这种作用在选择性 AMPK 抑制剂化合物 C 的存在下被逆转。此外，Rg(1) 以时间和浓度依赖的方式显著诱导肝激酶 B1 (LKB1)、AMPK 和叉头框 O1 (FoxO1) 的磷酸化，FoxO1 是糖异生酶的关键转录因子。当细胞暴露于 40 μM 的 Rg(1) 时，葡萄糖-6-磷酸酶 (G6Pase) 和磷酸烯醇丙酮酸羧激酶 (PEPCK) 活性分别被抑制 24%和 21%，这是由于 FoxO1 的磷酸化和糖异生基因表达的抑制。总之，我们的结果表明 Rg(1) 通过 LKB1-AMPK-FoxO1 途径抑制 HepG2 人肝癌细胞的肝葡萄糖生成。
