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Caffeic acid phenethyl ester suppresses intestinal FXR signaling and ameliorates nonalcoholic fatty liver disease by inhibiting bacterial bile salt hydrolase activity

文献类型：期刊论文

作者Zhong, Xian-Chun2,3; Liu, Ya-Meng2; Gao, Xiao-Xia1; Krausz, Kristopher W.1; Niu, Bing3; Gonzalez, Frank J.1; Xie, Cen1,2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2022-06-02
页码12
ISSN号1671-4083
关键词nonalcoholic fatty liver disease caffeic acid phenethyl ester bile salt hydrolase farnesoid X receptor ceramide gut microbiota
DOI10.1038/s41401-022-00921-7
通讯作者Gonzalez, Frank J.(gonzalef@mail.nih.gov) ; Xie, Cen(xiecen@simm.ac.cn)
英文摘要Propolis is commonly used in traditional Chinese medicine. Studies have demonstrated the therapeutic effects of propolis extracts and its major bioactive compound caffeic acid phenethyl ester (CAPE) on obesity and diabetes. Herein, CAPE was found to have pharmacological activity against nonalcoholic fatty liver disease (NAFLD) in diet-induced obese mice. CAPE, previously reported as an inhibitor of bacterial bile salt hydrolase (BSH), inhibited BSH enzymatic activity in the gut microbiota when administered to mice. Upon BSH inhibition by CAPE, levels of tauro-beta-muricholic acid were increased in the intestine and selectively suppressed intestinal farnesoid X receptor (FXR) signaling. This resulted in lowering of the ceramides in the intestine that resulted from increased diet-induced obesity. Elevated intestinal ceramides are transported to the liver where they promoted fat production. Lowering FXR signaling was also accompanied by increased GLP-1 secretion. In support of this pathway, the therapeutic effects of CAPE on NAFLD were absent in intestinal FXR-deficient mice, and supplementation of mice with C16-ceramide significantly exacerbated hepatic steatosis. Treatment of mice with an antibiotic cocktail to deplete BSH-producing bacteria also abrogated the therapeutic activity of CAPE against NAFLD. These findings demonstrate that CAPE ameliorates obesity-related steatosis at least partly through the gut microbiota-bile acid-FXR pathway via inhibiting bacterial BSH activity and suggests that propolis enriched with CAPE might serve as a promising therapeutic agent for the treatment of NAFLD.
WOS关键词FARNESOID-X-RECEPTOR ; GUT MICROBIOTA
资助项目National Key Research and Development Program of China[2021YFA1301200] ; National Natural Science Foundation of China[91957116] ; National Natural Science Foundation of China[82104261] ; China Postdoctoral Science Foundation[2020M671269] ; Shanghai Municipal Science and Technology Major Project ; Center for Cancer Research, National Cancer Institute, National Institutes of Health
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBL GROUP
WOS记录号WOS:000805103300002
源URL[http://119.78.100.183/handle/2S10ELR8/301228]  
专题新药研究国家重点实验室
通讯作者Gonzalez, Frank J.; Xie, Cen
作者单位1.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China
推荐引用方式
GB/T 7714		 Zhong, Xian-Chun,Liu, Ya-Meng,Gao, Xiao-Xia,et al. Caffeic acid phenethyl ester suppresses intestinal FXR signaling and ameliorates nonalcoholic fatty liver disease by inhibiting bacterial bile salt hydrolase activity[J]. ACTA PHARMACOLOGICA SINICA,2022:12.
APA Zhong, Xian-Chun.,Liu, Ya-Meng.,Gao, Xiao-Xia.,Krausz, Kristopher W..,Niu, Bing.,...&Xie, Cen.(2022).Caffeic acid phenethyl ester suppresses intestinal FXR signaling and ameliorates nonalcoholic fatty liver disease by inhibiting bacterial bile salt hydrolase activity.ACTA PHARMACOLOGICA SINICA,12.
MLA Zhong, Xian-Chun,et al."Caffeic acid phenethyl ester suppresses intestinal FXR signaling and ameliorates nonalcoholic fatty liver disease by inhibiting bacterial bile salt hydrolase activity".ACTA PHARMACOLOGICA SINICA (2022):12.

入库方式： OAI收割

来源：上海药物研究所

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