20S-Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic stellate cell apoptosis through LKB1-AMPK activation

Publication date: Available online 25 January 2017 Source:Journal of Ginseng Research Author(s): Sang Mi Park, Eun Hye Jung, Jae Kwang Kim, Kyung Hwan Jegal, Chung A. Park, Il Je Cho, Sang Chan Kim Background Previously, we reported Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing numbers of HSCs and the underlying mechanism involved. Methods Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT assays were conducted to examine the cytotoxic effects of ginsenosides. H2O2 productions, glutathione contents, lactate dehydrogenase activities, mitochondrial membrane permeabilities, apoptotic cell subpopulations, caspase-3/7 activities, TUNEL staining, and immunoblot analysis were performed to elucidate the molecular mechanism responsible for ginsenoside-mediated cytotoxicity. Involvement of the AMP-activated protein kinase (AMPK)-related signaling pathway was examined using a chemical inhibitor and siRNA transfection. Results and conclusion Of the 11 ginsenosides tested, 20S-protopanaxadiol (PPD) showed the most potent cytotoxic activity in both LX-2 cells and primary activated HSCs. Oxidative stress-mediated apoptosis induced by 20S-PPD was blocked by N-acetyl-L-cysteine pretreatment. In addition, 20S-PPD concentration-dependently increased the phosphorylation of AMPK,...
Source: Journal of Ginseng Research - Category: Complementary Medicine Source Type: research