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

In Yu Lin, Yi Shiou Chiou, Li Ching Wu, Chen Yu Tsai, Chiung Tong Chen, Wu Chang Chuang, Ming Chung Lee, Ching Che Lin, Ting Ting Lin, Ssu Ching Chen, Min Hsiung Pan, Nianhan Ma

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)184-194
Number of pages11
JournalJournal of Food and Drug Analysis
Volume27
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • Antrodia cinnamomea
  • Liver fibrosis
  • STAT3 pathway
  • TGF-β pathway
  • Wnt pathway

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