Ginsenoside AD-2 Ameliorating Lipopolysaccharide-Induced Activation in HSC-T6 Cells and Carbon Tetrachloride-Induced Hepatic Fibrosis in Mice via Regulation of VD-VDR Axis

Ginsenoside 25-hydroxy protopanaxadiol (AD-2) isolated from ginseng was proved to have anti-hepatic fibrosis (HF) effect in our previous study. But the mechanism is unknown. The present study investigated the anti-HF effects and mechanisms of AD-2 on the lipopolysaccharide (LPS)-induced activation in HSC-T6 cells and carbon tetrachloride (CCl₄)-induced hepatic fibrosis (HF) in mice. Results showed that AD-2 significantly inhibited the LPS-induced activated HSC-T6 cells in vitro and markedly reduced the serum transaminase and hydroxyproline levels, pathological changes, and hepatic body ratio in CCl₄-induced HF mice, indicating AD-2 ameliorated liver injury and reversed HF notably. Moreover, AD-2 decreased the expression of TGF-β1, α-SMA, and MMP2, and maintained TIMP1/MMP9 in balance with the level of vitamin D (VD) and the expression of VD nuclear receptor (VDR) and Sirt3 increased. In conclusion, the anti-HF mechanism of AD-2 is related to the inhibition of HSC activation, promotion of collagen degradation, and regulation of the VD/VDR axis.