CCM111 prevents hepatic fibrosis via cooperative inhibition of TGF-β Wnt and STAT3 signaling pathways

CCM111 is an aqueous extract of Antrodia cinnamomea (AC) that has exhibited anti-liver fibrosis functions. However, the detailed mechanisms of AC action against liver fibrosis have not been elucidated yet. The present research showed that CCM111 significantly lowered the levels of the hepatic enzyme markers glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT), prevented liver damage and collagen deposition, and downregulated TGF-β/Smad signaling in a dose-dependent manner compared with CCl₄ treatment alone. CCM111 markedly inhibited TGF-β Wnt and STAT3 signaling pathway-regulated downstream genes in the liver by next-generation sequencing. The antifibrotic mechanisms of CCM111 were further demonstrated in HSC-T6 cells. Our data demonstrated for the first time that CCM111 can protect against CCl₄-induced liver fibrosis by the cooperative inhibition of TGF-β-, Wnt- and STAT3-dependent proinflammatory and profibrotic mediators, suggesting that CCM111 might be a candidate for preventing and treating chronic fibrotic liver diseases.