Tetrandrine inhibits activation of rat hepatic stellate cells stimulated by transforming growth factor-beta in vitro via up-regulation of Smad 7.
Tetrandrine is a bisbenzylisoquinoline alkaloid derived from the root of a Chinese herbal medicine Stephania tetrandra S. Moore, which has been used traditionally for the treatment of hepatofibrogenic disease in China for several decades. In the present study, the inhibitory effects of tetrandrine lower concentrations (0.25, 0.5, 1, 2 mg/L) on culture-activation and transforming growth factor-beta(1) (TGF-beta(1))-stimulated activation of quiescent rat hepatic stellate cells (HSCs) in vitro were assessed, and the possible relations between the underlying mechanism of these effects and TGF-beta signaling via its receptors were investigated. As shown by the examination of alpha-SMA using immunocytochemical staining or Western blot, tetrandrine inhibited both culture-activation and TGF-beta(1)-stimulated activation of HSCs. Further investigations revealed that, in this process, TGF-beta(1) mRNA expression was suppressed significantly in contrast to an up-regulation of Smad 7, while the expressions of type I and type II TGF-beta(1) receptors and Smad 3 mRNA were insignificantly changed by tetrandrine. These results suggest that tetrandrine at lower concentrations has a significant inhibiting effect on culture-activation and TGF-beta(1)-stimulated activation of rat HSCs, and that it may be due to an up-regulation of Smad 7 which in turn blocks TGF-beta(1) expression and its downstream signaling.
Chen
Yuan-wen
YW
Digestive Disease Laboratory, Xinhua Hospital, Shanghai Second Medical University, Shanghai 200092, PR China. shsmus@263.net
Li
Ding-guo
DG
Wu
Jian-xin
JX
Chen
Ying-wei
YW
Lu
Han-ming
HM
D000199:Actins / Q000096:biosynthesis; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008099:Liver / Q000166:cytology* / Q000187:drug effects*; D018517:Plant Roots / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects
D000199:Actins; D000470:Alkaloids; D044182:Benzylisoquinolines; D007202:Indicators and Reagents; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C009438:tetrandrine