The common dietary flavonoid myricetin attenuates liver fibrosis in carbon tetrachloride treated mice

Scope: Myricetin is found in most berries, vegetables, and various medicinal herbs, which has been reported to possess various bio-activities. However, the role of myricetin on liver fibrosis remains to be elucidated. Methods and results: Hepatic stellate cell (HSC) line CFSC-8B was stimulated by transforming growth factor beta 1 (TGF-beta 1) or platelet-derived growth factor BB (PDGF-BB) to induce liver fibrosis in vitro. The results showed that myricetin significantly ameliorated TGF-beta 1- or PDGF-BB-induced HSCs activation, cell migration, and extracellular matrix production; blocked TGF-beta 1-induced phosphorylation of Smad2, P38, extracellular signal-regulated kinase (ERK), and protein kinase B (Akt); and downregulated PDGF-BB stimulated phosphorylation of extracellular signal-regulated kinase and Akt in HSCs in a dose-dependent manner. Meanwhile, the carbon tetrachloride (CCl4) induced mouse model has been used to study antifibrosis role of myricetin in vivo. Our data demonstrated that myricetin suppressed alpha-smooth muscle actin and collagen type I deposition and blocked phosphorylation of Smad2, mitogen-activated protein kinases, and Akt in CCl4-treated mice. Conclusion: Myricetin inhibits the activation of HSCs and ameliorates CCl4-induced liver fibrosis in mice and may serve as a potential therapeutic agent in the treatment of liver fibrosis.