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.
BACKGROUND
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.


OBJECTIVE
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.


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 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 24h 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.
School of Traditional Chinese Medicine,Chang Gung University;  Liver Research Center,Chang Gung Memorial Hospital,Taoyuan,Taiwan. pan@mail.cgu.edu.tw
Tai-Long
TL
Pan
Pei-Wen
PW
Wang
Yann-Lii
YL
Leu
Tung-Ho
TH
Wu
Tian-Shung
TS
Wu
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009130:Muscle, Smooth / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D031364:Scutellaria baicalensis; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000199:Actins; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; C499814:Scutellaria baicalensis extract; D051028:bcl-2-Associated X Protein; D003094:Collagen; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D004128:Dimethylnitrosamine