Shanghai Institute of Materia Medica, Pudong, China.
Biol Pharm Bull. 2009 Sep;32(9):1533-7. doi: 10.1248/bpb.32.1533.
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 microg/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 CCl(4)-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.
肝星状细胞（HSCs）的增殖是肝损伤时纤维化发展的核心。本研究旨在确定小檗碱是否能抑制体外 HSC 增殖并预防体内实验性肝纤维化。用不同浓度（0-20 μg/ml）的小檗碱孵育激活的大鼠肝星状细胞（CFSCs）。孵育 48 小时后，小檗碱显著抑制 CFSC 增殖，并诱导细胞周期停滞在 G1 期。实时和 Western blot 显示，小檗碱明显降低了 p21 和 p27 的表达。小檗碱还降低了 Akt 磷酸化和 FoxO1 磷酸化，导致 FoxO1 核转位。小檗碱能有效预防 CCl4 诱导的小鼠肝纤维化，同时减少激活的 HSCs 数量。因此，小檗碱通过抑制肝星状细胞增殖来预防肝纤维化。
