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18 beta-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway

文献类型：期刊论文

作者Wu, Shou-yan1,2; Cui, Shi-chao2,3; Wang, Le1,2; Zhang, Yi-ying1,2; Yan, Xiao-xia1,2; Lu, Heng-lei1,2; Xing, Guo-zhen1,2; Ren, Jin1,2; Gong, Li-kun1,2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2018-12-01
卷号39期号:12页码:1865-1873
关键词hepatoprotective effect cholestatic liver injury 18 beta-glycyrrhetinic acid (18b-GA) FXR Sirt1 bile acid transporters
ISSN号1671-4083
DOI10.1038/s41401-018-0110-y
通讯作者Gong, Li-kun(lkgong@cdser.simm.ac.cn)
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, 18 beta-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, significantly 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.
WOS关键词INDUCED LIVER-INJURY ; SANDWICH-CULTURED RAT ; NAPHTHYL ISOTHIOCYANATE ; GLYCYRRHETINIC ACID ; BILE-ACIDS ; GLYCYRRHIZIN ; TRANSPORTERS ; FXR ; EXPRESSION ; DELETION
资助项目National New Drug Creation Program of China[2018ZX09201017-004] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050305] ; National Natural Science Foundation of China[81403028]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000454773800006
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/290796]  
专题新药研究国家重点实验室
通讯作者Gong, Li-kun
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Shou-yan,Cui, Shi-chao,Wang, Le,et al. 18 beta-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway[J]. ACTA PHARMACOLOGICA SINICA,2018,39(12):1865-1873.
APA Wu, Shou-yan.,Cui, Shi-chao.,Wang, Le.,Zhang, Yi-ying.,Yan, Xiao-xia.,...&Gong, Li-kun.(2018).18 beta-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway.ACTA PHARMACOLOGICA SINICA,39(12),1865-1873.
MLA Wu, Shou-yan,et al."18 beta-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway".ACTA PHARMACOLOGICA SINICA 39.12(2018):1865-1873.

入库方式： OAI收割

来源：上海药物研究所

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