Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-β1/Smads signaling pathway modulation

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• 作者：Yuping Zhou^a ; Xin Tong^a ; Shuang Ren^a ; Xiaoling Wang^c ; Jiamei Chen^a ; Yongping Mu^a ; Mingyu Sun^a ; Gaofeng Chen^a ; Hua Zhang^a ; Ping Liu^a ; ^b ; ^{liuliver@vip.sina.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ALT ; alanine aminotransferase ; α-SMA ; α-smooth muscle actin ; AST ; total astragalus saponins ; BDL ; bile duct ligation ; DMN ; dimethylnitrosamine ; ECM ; extracellular matrix ; GA ; glycyrrhizic acid ; GAPDH ; glyceraldehyde-3-phosphate dehydrogenase ; HSCs ; hepatic stellate cells ; Hyp ; hydroxyproline ; LDH ; lactate dehydrogenase ; TGF-β1 ; transforming growth factor-β1 ; TGF-βRI ; transforming growth factor-β receptor I ; UDCA ; ursodeoxycholic acid
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：22 August 2016
• 年：2016
• 卷：190
• 期：Complete
• 页码：83-90
• 全文大小：4118 K

文摘

Huangqi decoction (HQD) is a well-known traditional Chinese herbal formulation, It is an effective treatment for consumptive disease and chronic liver diseases. It consists of Radix Astragali (Astragalus membranceus(Fisch.) Bge. Root, Huangqi) and Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch., root and rhizome, Gancao). Total astragalus saponins (AST) is a main component of Radix Astragali and glycyrrhizic acid(GA) is a main component of Radix Glycyrrhizae. Our primary results showed that the combination of AST and GA had an obvious synergistic effect in reducing liver collagen deposition and decreasing serum alanine aminotransferase (ALT) activity in dimethylnitrosamine (DMN)-induced liver fibrosis.

Aim of the study

Through in vivo and in vitro experiments, we aimed at investigating the key anti-fibrosis signal pathway TGF-β1/Smads to further explore the synergistic mechanism of AST and GA.

Material and methods

Two hepatic fibrosis animal models, bile duct ligation-induced (BDL) and DMN-induced, were utilized. Rats were treated orally with AST, GA or AST/GA, with the effects evaluated via liver histopathology, hydroxyproline (Hyp) levels, and α-SMA expression. In the hepatic stellate cell line JS-1, cells were treated with AST/GA for 24 h, followed by a cell viability assessment using Cell Counting Kit-8(CCK-8) and Real-time PCR and Western blot analysis of α-SMA, ColⅠ and TGF-β1/Smads signaling pathway related components.

Results

The AST/GA combination attenuated liver tissue inflammation, collagen deposition, Hyp levels, and α-SMA expression in both BDL-and DMN-stimulated hepatic fibrosis rats. In vitro results showed that the AST/GA combination significantly inhibited JS-1 cell viability, significantly suppressed α-SMA, ColⅠ, TGF-β1, Smad2 and Smad3 mRNA and protein expression, as well reduced p-Smad2/3. Compared with AST or GA treatment alone, the AST/GA combination significantly reduced Smad3 mRNA expression levels and TGF-β1, Smad3, and p-Smad2/3 protein levels.

Conclusions

AST and GA synergistically alleviated both BDL-and DMN-induced hepatic fibrosis via TGF-β1/Smads signaling pathway inhibition in hepatic stellate cells.