Proliferation of hepatic stellate cells (HSCs) is central for the development of fibrosis during liver injury. Our aim in this study was to determine whether berberine could inhibit HSC proliferation in vitro and prevent experimental liver fibrosis in vivo. Activated rat hepatic stellate cells (CFSCs) were incubated with various concentrations (0—20 μg/ml) of berberine. After 48 h incubation, berberine significantly inhibited CFSC proliferation and induced cell cycle arrest in G1 phase. Real-time and Western blotting revealed that both p21 and p27 expression was markedly reduced by berberine. Berberine also decreased Akt phosphorylation and FoxO1 phosphorylation, which led to FoxO1 nuclear translocation. Berberine effectively prevented CCl4-induced liver fibrosis in mice, which was accompanied by a decrease in the number of activated HSCs. Thus, berberine was able to prevent liver fibrosis by inhibition of hepatic stellate cell proliferation.
2009 The Pharmaceutical Society of Japan