Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-β1/Smads signaling pathway modulation.
Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-β1/Smads signaling pathway modulation.
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DOI：
10.1016/j.jep.2016.06.011
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发表时间：
2016-08
影响因子：
5.4
通讯作者：
Yuping Zhou;X. Tong;Shuang Ren;Xiaoling Wang;Jiamei Chen;Y. Mu;Mingyu Sun;Gaofeng Chen;Hua Zhang;Ping Liu
中科院分区：
文献类型：
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作者：
Yuping Zhou;X. Tong;Shuang Ren;Xiaoling Wang;Jiamei Chen;Y. Mu;Mingyu Sun;Gaofeng Chen;Hua Zhang;Ping Liu
民族药理学相关性黄芪汤是著名的传统中药方剂，是治疗虚劳性疾病和慢性肝病的有效药物。黄芪（Astragalusmembranceus（菲施.）BGE.根，黄芪）和甘草（RizhiuralensisFisch.，根和根茎，Gancao）。黄芪总皂苷（AST）是黄芪的主要成分，黄芪酸（GA）是黄芪的主要成分。我们的初步研究结果表明，AST和GA联合应用在减少二甲基亚硝胺（DMN）诱导的肝纤维化中的肝胶原沉积和降低血清丙氨酸氨基转移酶（ALT）活性方面具有明显的协同作用。我们旨在研究关键的抗纤维化信号通路TGF-β1/材料与方法采用胆管结扎（BDL）和DMN诱导的肝纤维化动物模型。以肝组织病理学、羟脯氨酸（Hyp）水平和α-SMA表达为指标，观察AST、GA或AST/GA对大鼠肝纤维化的影响。在肝星状细胞系JS-1中，用AST/GA处理细胞24 h，然后使用细胞计数试剂盒（CCK-8）和实时PCR和Western印迹分析α-SMA、ColⅠ和TGF-β1/Smads信号通路相关组分来评估细胞活力。体外实验结果显示，AST/GA联合应用可显著抑制肝纤维化大鼠肝细胞JS-1的存活率，抑制α-SMA、ColⅠ、TGF-β1、Smad 2和Smad 3的mRNA和蛋白表达，并降低p-Smad 2/3的表达。结论AST和GA通过抑制肝星状细胞TGF-β1/Smads信号通路，协同减轻BDL和DMN诱导的肝纤维化。
Ethnopharmacological relevanceHuangqi 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 (Astragalusmembranceus(Fisch.)Bge. Root, Huangqi) and Radix Glycyrrhizae (Glycyrrhiza uralensisFisch.,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 studyThroughin vivoandin vitroexperiments, 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 methodsTwo 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 evaluatedvialiver 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.ResultsThe 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 vitroresults 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.ConclusionsAST and GA synergistically alleviated both BDL-and DMN-induced hepatic fibrosisviaTGF-β1/Smads signaling pathway inhibition in hepatic stellate cells.