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 relevanceThe 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 studyThe 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 methodsDimethylnitrosamine (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.ResultsHepatic collagen contents and alpha-smooth muscle actin levels were remarkably reduced by treating with SBEE. 100 μg/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 G2/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.ConclusionsThese findings demonstrated that SBEE could prevent hepatic fibrosis by promoting ERK-p53 pathways which may in turn cause G2/M cell cycle arrest and activate caspase system resulting in final apoptosis of HSC-T6 cells.

Graphical abstractSBEE could prevent hepatic fibrosis in vivo and promote ERK-p53 pathways which lead to G2/M arrest and activate caspase system resulting in apoptosis of activated HSC-T6 cells.Download high-res image (243KB)Download full-size image