Compound Astragalus and Salvia miltiorrhiza Extract exerts anti-fibrosis by mediating TGF-β/Smad signaling in myofibroblasts

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• 作者：Yan Yang ; Sen Yang ; Minzhu Chen ; Xiaoxiang Zhang ; Yuhong Zou ; Xuejun Zhang
• 关键词：Compound Astragalus and Salvia miltiorrhiza Extract (CASE) ; Astragalus membranaceus Bunge (Leguminosae) ; Salvia miltiorhiza Bunge (Lamiaceae) ; Transforming growth factor-β ; Smad ; Myofibroblast ; Hepatic fibro
• 刊名：Journal of Ethnopharmacology
• 出版年：2008
• 出版时间：23 July 2008
• 年：2008
• 卷：118
• 期：2
• 页码：264-270
• 全文大小：967 K

文摘

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 -smooth muscle actin (-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.