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

• Published in: Scientific reports Vol. 8; no. 1; pp. 15367 - 11
• Main Authors: Cai, Fei-Fei, Wu, Rong, Song, Ya-Nan, Xiong, Ai-Zhen, Chen, Xiao-Le, Yang, Meng-Die, Yang, Li, Hu, Yuanjia, Sun, Ming-Yu, Su, Shi-Bing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.10.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 14/5; 692/4020/4021/1607/1605; 692/4020/4021/288/2140; 82/1; Acids; Bile; Chenodeoxycholic acid; Chenodeoxycholic Acid (CDCA); Dimethylnitrosamine; Excretion; Extracellular signal-regulated kinase; Fibrosis; Hepatic Stellate Cells (HSC); Humanities and Social Sciences; Liquid chromatography; Liver; Mass spectroscopy; Metabolism; multidisciplinary; Reabsorption; Regulates Bile Acid Metabolism; Science; Science (multidisciplinary); Signal transduction; Smad protein; Smad3 protein; Stellate cells; Toxic Bile Acids; Transforming growth factor-b1; Western blotting; Yinchenhao; Toxic Bile Acids; Hepatic Stellate Cells (HSC); Chenodeoxycholic Acid (CDCA); Yinchenhao; Regulates Bile Acid Metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-33669-4

Yinchenhao decoction (YCHD), comprising Yinchenhao ( 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 of YCHD 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 that YCHD 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 α-SMA, TGF-β1, 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-β1/Smad/ERK signalling pathway.