Antrodia camphorata-Derived Antrodin C Inhibits Liver Fibrosis by Blocking TGF-Beta and PDGF Signaling Pathways

Hepatic stellate cells (HSCs) play an essential role in the development of liver fibrosis. Antrodia camphorata (A. camphorata) is a medicinal fungus with hepatoprotective effect. This study investigated whether Antrodin C, an A. camphorata-fermented metabolite, could exert a protective role on liver fibrosis both in vitro and in vivo. The anti-fibrotic effect of Antrodin C was investigated in CFSC-8B cell (hepatic stellate cell) stimulated by transforming growth factor-beta 1 (TGF-beta 1) or platelet-derived growth factor-BB (PDGF-BB) in vitro and in CCl4 induced liver fibrosis in mice. Antrodin C (50 mu M) inhibited TGF-beta 1 or PDGF-BB stimulated CFSC-8B cell activation, migration and extracellular matrix (ECM) accumulation (all p < 0.05). Antrodin C (3, 6 mg/kg/d) oral administration reduced the degree of liver fibrosis induced by CCl4 in mice. Antrodin C down-regulated the expression of alpha-smooth muscle actin (alpha-SMA) and collagen I in fibrotic livers. Furthermore, Antrodin C ameliorated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation in serum (all p < 0.05). Mechanistically, Antrodin C executes its anti-fibrotic activity through negatively modulate TGF-beta 1 downstream SMAD Family Member 2 (Smad2), AKT Serine/Threonine Kinase 1 (AKT), extracellular signal-regulated kinase (ERK), and P38 MAP Kinase (P38), as well as PDGF-BB downstream AKT and ERK signaling pathways. Antrodin C ameliorates the activation, migration, ECM production in HSCs and CCl4-induced liver fibrosis in mice, suggesting that Antrodin C could serve as a protective molecule against liver fibrosis.

Automated summary

This study investigated the protective effect of Antrodin C, a fermented metabolite of Antrodia camphorata, on liver fibrosis. The results showed that Antrodin C inhibited the activation, migration, and extracellular matrix accumulation of hepatic stellate cells, and reduced the degree of CCl4-induced liver fibrosis. Antrodin C also improved the abnormal levels of liver enzymes in serum. Mechanistically, Antrodin C exerted its anti-fibrotic activity through modulation of several signaling pathways. Overall, Antrodin C could serve as a protective molecule against liver fibrosis.