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

Abstract 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)-induce...

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Autores principales:	Fei-Fei Cai, Rong Wu, Ya-Nan Song, Ai-Zhen Xiong, Xiao-Le Chen, Meng-Die Yang, Li Yang, Yuanjia Hu, Ming-Yu Sun, Shi-Bing Su
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Toxic Bile Acids Yinchenhao Regulates Bile Acid Metabolism Hepatic Stellate Cells (HSC) Chenodeoxycholic Acid (CDCA) Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ef12ecebcbb74ec7bc6d968286ef2563
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spelling	oai:doaj.org-article:ef12ecebcbb74ec7bc6d968286ef25632021-12-02T15:08:52ZYinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway10.1038/s41598-018-33669-42045-2322https://doaj.org/article/ef12ecebcbb74ec7bc6d968286ef25632018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33669-4https://doaj.org/toc/2045-2322Abstract 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.Fei-Fei CaiRong WuYa-Nan SongAi-Zhen XiongXiao-Le ChenMeng-Die YangLi YangYuanjia HuMing-Yu SunShi-Bing SuNature PortfolioarticleToxic Bile AcidsYinchenhaoRegulates Bile Acid MetabolismHepatic Stellate Cells (HSC)Chenodeoxycholic Acid (CDCA)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toxic Bile Acids Yinchenhao Regulates Bile Acid Metabolism Hepatic Stellate Cells (HSC) Chenodeoxycholic Acid (CDCA) Medicine R Science Q
spellingShingle	Toxic Bile Acids Yinchenhao Regulates Bile Acid Metabolism Hepatic Stellate Cells (HSC) Chenodeoxycholic Acid (CDCA) Medicine R Science Q Fei-Fei Cai Rong Wu Ya-Nan Song Ai-Zhen Xiong Xiao-Le Chen Meng-Die Yang Li Yang Yuanjia Hu Ming-Yu Sun Shi-Bing Su Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway
description	Abstract 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.
format	article
author	Fei-Fei Cai Rong Wu Ya-Nan Song Ai-Zhen Xiong Xiao-Le Chen Meng-Die Yang Li Yang Yuanjia Hu Ming-Yu Sun Shi-Bing Su
author_facet	Fei-Fei Cai Rong Wu Ya-Nan Song Ai-Zhen Xiong Xiao-Le Chen Meng-Die Yang Li Yang Yuanjia Hu Ming-Yu Sun Shi-Bing Su
author_sort	Fei-Fei Cai
title	Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway
title_short	Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway
title_full	Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway
title_fullStr	Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway
title_full_unstemmed	Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway
title_sort	yinchenhao decoction alleviates liver fibrosis by regulating bile acid metabolism and tgf-β/smad/erk signalling pathway
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/ef12ecebcbb74ec7bc6d968286ef2563
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Yinchenhao Decoction Alleviates Liver Fibrosis by Regulating Bile Acid Metabolism and TGF-β/Smad/ERK Signalling Pathway

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