20 S -Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic stellate cell apoptosis through liver kinase B1-AMP-activated protein kinase activation.

Of the 11 ginsenosides tested, 20-protopanaxadiol (PPD) showed the most potent cytotoxic activity in both LX-2 cells and primary activated HSCs. Oxidative stress-mediated apoptosis induced by 20-PPD was blocked by -acetyl-l-cysteine pretreatment. In addition, 20-PPD concentration-dependently increased the phosphorylation of AMPK, and compound C prevented 20-PPD-induced cytotoxicity and mitochondrial dysfunction. Moreover, 20-PPD increased the phosphorylation of liver kinase B1 (LKB1), an upstream kinase of AMPK. Likewise, transfection of LX-2 cells with LKB1 siRNA reduced the cytotoxic effect of 20-PPD. Thus, 20-PPD appears to induce HSC apoptosis by activating LKB1-AMPK and to be a therapeutic candidate for the prevention or treatment of liver fibrosis.