18glycyrrhetinicacidprotectsagainstalphanaphthylisothiocyanateinducedcholestasisthroughactivationofthesirt1fxrsignalingpathway

	18glycyrrhetinicacidprotectsagainstalphanaphthylisothiocyanateinducedcholestasisthroughactivationofthesirt1fxrsignalingpathway
	Shouyan Wu 1; Shichao Cui 2; Le Wang 1; Yiting Zhang 1; Xiaoxia Yan 1; Henglei Lu 1; Guozhen Xing 1; Jin Ren 1; Likun Gong 1
刊名	中国药理学报英文版
	2018
卷号	039 期号:012 页码:1865
关键词	hepatoprotective effect cholestatic liver injury 18β-glycyrrhetinic acid (18b-GA) FXR Sirt1 bile acid transporters
ISSN号	1671-4083
英文摘要	Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18β-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect. According to the results, 18b-GA markedly attenuated ANIT-induced liver injury as indicated the hepatic plasma chemistry index and histopathology examination. In addition, the expression levels of nuclear factors, including Sirt1, FXR and Nrf2, and their target efflux transporters in the liver, which mainly mediate bile acid homeostasis in hepatocytes, signi?cantly increased. Furthermore, we first revealed that 18b-GA treatment significantly activated FXR, and which can be significantly reduced by EX-527 (a potent and selective Sirt1 inhibitor), indicating that 18b-GA activates FXR through Sirt1. Taken together, 18b-GA confers hepatoprotection against ANIT-induced cholestasis by activating FXR through Sirt1, which promotes gene expression of the efflux transporter, and consequently attenuates dysregulation of bile acid homeostasis in hepatocyte compartments.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/284108]
专题	中国科学院上海药物研究所
作者单位	1.Center for Drug Safety Evaluation and Research,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences 2.中国科学院大学 3.State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences
推荐引用方式 GB/T 7714	Shouyan Wu,Shichao Cui,Le Wang,et al. 18glycyrrhetinicacidprotectsagainstalphanaphthylisothiocyanateinducedcholestasisthroughactivationofthesirt1fxrsignalingpathway[J]. 中国药理学报英文版,2018,039(012):1865.
APA	Shouyan Wu.,Shichao Cui.,Le Wang.,Yiting Zhang.,Xiaoxia Yan.,...&Likun Gong.(2018).18glycyrrhetinicacidprotectsagainstalphanaphthylisothiocyanateinducedcholestasisthroughactivationofthesirt1fxrsignalingpathway.中国药理学报英文版,039(012),1865.
MLA	Shouyan Wu,et al."18glycyrrhetinicacidprotectsagainstalphanaphthylisothiocyanateinducedcholestasisthroughactivationofthesirt1fxrsignalingpathway".中国药理学报英文版 039.012(2018):1865.