Inhibitory effects of Scutellaria baicalensis extract on hepatic stellate cells through inducing G2/M cell cycle arrest and activating ERK-dependent apoptosis via Bax and caspase pathway

Ethnopharmacological relevance: The bioactive components extracted from Scutellaria baicalensis Georgi (SB) have been widely used for anti-cancer, anti-oxidation, anti-inflammation and modulating the immune response. Aim of the study: The purpose of this study is to verify the inhibitory effect and the underlying mechanisms of Scutellaria baicalensis ethanol extract (SBEE) on activated hepatic stellate cells which play a central role in liver fibrogenesis. Materials and methods: Dimethylnitrosamine (DMN)-administrated rat model was applied to evaluate the anti-fibrotic effect of SBEE in vivo. Flow cytometric analysis and immunoblotting were then used to further investigate the molecular mechanisms by which Scutellaria baicalensis extract induces HSC-T6 cell death. Results: Hepatic collagen contents and alpha-smooth muscle actin levels were remarkably reduced by treating with SBEE. 100 mu g/mL SBEE-induced apoptosis of HSC-T6 cell was characterized with elevated levels of activated caspase-3, poly-(ADP-ribose) polymerase (PARP) cleavage, and release of cytochrome c into the cytosol in a time-dependent manner. A 24 h treatment of SBEE induced G(2)/M cell cycle arrest with increased expression of p21 and downregulation of cdc2 and cyclin B1 protein levels. Again, SBEE induced bax expression with concomitant decrease of bcl-2 and upregulated the p53 and MAPK signaling in HSC-T6 cells. Conclusions: These findings demonstrated that SBEE could prevent hepatic fibrosis by promoting ERK-p53 pathways which may in turn cause G(2)/M cell cycle arrest and activate caspase system resulting in final apoptosis of HSC-T6 cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.