Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway

被引：75

作者：

Cai, Fei-Fei ^{[1
]}

Wu, Rong ^{[1
]}

Song, Ya-Nan ^{[1
]}

Xiong, Ai-Zhen ^{[2
]}

Chen, Xiao-Le ^{[1
]}

Yang, Meng-Die ^{[1
]}

Yang, Li ^{[2
]}

Hu, Yuanjia ^{[3
]}

Sun, Ming-Yu ^{[4
]}

Su, Shi-Bing ^{[1
]}

机构：

[1] Shanghai Univ Tradit Chinese Med, Res Ctr forTradit Chinese Med Complex Syst, Shanghai, Peoples R China

[2] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardizat Chinese Med, Shanghai, Peoples R China

[3] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China

[4] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Liver Dis Inst, Shanghai, Peoples R China

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

美国国家科学基金会;

关键词：

HEPATIC STELLATE CELLS; WNT/BETA-CATENIN PATHWAY; CHRONIC KIDNEY-DISEASE; TRADITIONAL USES; TUBULOINTERSTITIAL FIBROSIS; BIOMARKER IDENTIFICATION; METABOLOMICS INSIGHTS; OXIDATIVE STRESS; PODOCYTE INJURY; QUALITY-CONTROL;

D O I：

10.1038/s41598-018-33669-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Yinchenhao decoction (YCHD), comprisingYinchenhao (Artemisiae Scopariae Herba), Zhizi (Gardeniae Fructus) and Dahuang (Radix Rhei et Rhizoma), is widely used for treating various diseases. We aimed to investigate the bile acid metabolic mechanism ofYCHD in dimethylnitrosamine (DMN)-induced liver fibrosis model. Rats received DMN (10 mg/kg, intraperitoneally) for four successive weeks for liver fibrosis induction and were treated with YCHD for the last 2 weeks. Histopathological analysis showed that YCHD prevented DMN-induced histopathological changes in liver tissues. Serum liver function in YCHD group improved. Ultraperformance liquid chromatography-mass spectrometry analysis showed thatYCHD significantly restored both free and conjugated bile acid levels increased by DMN, to normal levels. RT-qPCR results showed that YCHD treatment upregulated the expression of genes related to bile acid synthesis, reabsorption, and excretion. Western blotting analysis showed that YCHD downregulated alpha-SMA,TGF-beta 1, p-Smad3, and p-ERK1/2 expression in chenodeoxycholic acid (CDCA)-activated hepatic stellate cells (HSCs). The viability of CDCA-activated HSCs significantly increased after treatment with YCHD and PD98059 (an ERK inhibitor) compared to YCHD treatment alone. Our findings suggest that YCHD alleviated DMN-induced liver fibrosis by regulating enzymes responsible for bile acid metabolism. Additionally, it inhibits CDCA-induced HSC proliferation and activation via TGF-beta 1/Smad/ERK signalling pathway.

引用

页数：11

共 59 条

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