Compound astragalus and salvia miltiorrhiza extract exerts anti-fibrosis by mediating TGF-beta/smad signaling in myofibroblasts

Yang, Yan, Yang, Sen, Chen, Minzhu, Zhang, Xiaoxiang, Zou, Yuhong and Zhang, Xuejun (2008) Compound astragalus and salvia miltiorrhiza extract exerts anti-fibrosis by mediating TGF-beta/smad signaling in myofibroblasts. Journal of Ethnopharmacology, 118 2: 264-270. doi:10.1016/j.jep.2008.04.012


Author Yang, Yan
Yang, Sen
Chen, Minzhu
Zhang, Xiaoxiang
Zou, Yuhong
Zhang, Xuejun
Title Compound astragalus and salvia miltiorrhiza extract exerts anti-fibrosis by mediating TGF-beta/smad signaling in myofibroblasts
Journal name Journal of Ethnopharmacology   Check publisher's open access policy
ISSN 0378-8741
Publication date 2008-07-01
Sub-type Article (original research)
DOI 10.1016/j.jep.2008.04.012
Open Access Status Not Open Access
Volume 118
Issue 2
Start page 264
End page 270
Total pages 7
Place of publication Ireland
Publisher Elsevier Ireland Ltd
Language eng
Formatted abstract
Previous studies showed that Compound Astragalus and Salvia miltiorrhiza Extract (CASE) has a protective effect against liver fibrosis. We hypothesized that CASE exerts the anti-fibrosis effect by mediating transforming growth factor-β (TGF-β)/Smad signaling pathway. To test this hypothesis, we induced fibrosis in rats by twice weekly injections of carbon tetrachloride (CCl4) and Smad2 phosphorylation was measured by immunohistochemical method; protein expression in myofibroblasts (MFBs) induced by TGF-β1 was analyzed by western blotting and plasminogen activator inhibitor type 1 (PAI-1) transcriptional activity in MFBs was evaluated. The present study showed that, in vivo, CASE has protective effects against liver fibrosis in rats generated by CCl4, and that CASE inhibits Smad2 phosphorylation at C-terminal region and expression of α-smooth muscle actin (α-SMA). Our experiment further demonstrated that, in vitro, (1) CASE inhibits TGF-β1-dependent Smad2 phosphorylation at C-terminal region and Smad2 and Smad3 phosphorylation at linker region in MFBs in a dose-dependent manner; (2) CASE decreases the level of Smad 2/3/4 complex in MFBs induced by TGF-β1 in a dose-dependent manner; (3) CASE inhibits PAI-1 transcriptional activity in MFBs induced by TGF-β1 in a dose-dependent manner; and (4) CASE markedly decreases c-Jun N-terminal kinase (JNK) phosphorylation in MFBs induced by TGF-β1. Our results suggest that CASE's anti-fibrosis effect in chronically injured liver was exerted by inhibiting TGF-β/Smads signal transduction.
Keyword Astragalus membranaceus Bunge (Leguminosae)
Compound Astragalus and Salvia miltiorrhiza Extract (CASE)
Hepatic fibrosis
Myofibroblast
Salvia miltiorhiza Bunge (Lamiaceae)
Smad
Transforming growth factor-β
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Thu, 03 Sep 2009, 19:40:44 EST by Mr Andrew Martlew on behalf of Medicine - Princess Alexandra Hospital