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Gardenia jasminoides Ellis. Polysaccharides Alleviated Cholestatic Liver Injury by Increasing the Production of Butyric Acid and FXR Activation

文献类型：期刊论文

作者Wang, Tianming2; Tian, Tian2; Zhu, Zhenyun1; Fang, Su1; Zhang, Lincong2; Peng, Xiaotian2; Shi, Rong2; Li, Yuanyuan2; Wu, Jiasheng2; Ma, Yueming2
刊名PHYTOTHERAPY RESEARCH
出版日期2024-09-05
页码13
关键词bile acid butyric acid cholestasis FXR Gardenia jasminoides Ellis. polysaccharide intestinal bacterial metabolite
ISSN号0951-418X
DOI10.1002/ptr.8326
通讯作者Wu, Jiasheng(wujiasheng@shutcm.edu.cn) ; Ma, Yueming(mayueming_117@hotmail.com)
英文摘要Gardenia jasminoides Ellis. polysaccharide (GPS) can protect against cholestatic liver injury (CLI) by regulating nuclear farnesoid X receptor (FXR).However, the mechanism via which GPS mediates the FXR pathway remains unclear. The aim of this study was to investigate the mechanism. Firstly, an alpha-naphthylisothiocyanate-induced cholestatic mouse model was administered with GPS to evaluate its hepatoprotective effects. The metabolic pathways influenced by GPS in cholestatic mice were detected by serum metabolomics. The effect of GPS on bile acid (BA) homeostasis, FXR expression, and liver inflammation were investigated. Second, the intestinal bacteria metabolites affected by GPS in vivo and in vitro were determined. The activation of FXR by sodium butyrate (NaB) was measured. Finally, the effects of NaB on cholestatic mice were demonstrated. The main pathways influenced by GPS involved BA biosynthesis. GPS upregulated hepatic FXR expression, improved BA homeostasis, reduced F4/80(+) and Ly6G(+) positive areas in the liver, and inhibited liver inflammation in cholestatic mice. Butyric acid was the most notable intestinal bacterial metabolite following GPS intervention. NaB activated the transcriptional activity of FXR in vitro, upregulated hepatic FXR and its downstream efflux transporter expression, and ameliorated disordered BA homeostasis in CLI mice. NaB inhibited the toll-like receptor 4/nuclear factor (TLR4/NF-kappa B) pathway and reduced inflammation and CLI in mice. An FXR antagonist suppressed the effects. In conclusion, GPS increased butyric acid production, which can activate hepatic FXR, reverse BA homeostasis disorder, and inhibit the TLR4/NF-kappa B inflammatory pathway, exerting protective effects against CLI.
WOS关键词GUT MICROBIOTA ; RECEPTOR FXR ; IMPACT
资助项目National Natural Science Foundation of China ; Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine[23KFL043] ; [81773871]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001307537900001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/313086]  
专题新药研究国家重点实验室
通讯作者Wu, Jiasheng; Ma, Yueming
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Analyt Res Ctr Organ & Biol Mol, State Key Lab Drug Res, Shanghai, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Sch Pharm, Dept Pharmacol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Tianming,Tian, Tian,Zhu, Zhenyun,et al. Gardenia jasminoides Ellis. Polysaccharides Alleviated Cholestatic Liver Injury by Increasing the Production of Butyric Acid and FXR Activation[J]. PHYTOTHERAPY RESEARCH,2024:13.
APA Wang, Tianming.,Tian, Tian.,Zhu, Zhenyun.,Fang, Su.,Zhang, Lincong.,...&Ma, Yueming.(2024).Gardenia jasminoides Ellis. Polysaccharides Alleviated Cholestatic Liver Injury by Increasing the Production of Butyric Acid and FXR Activation.PHYTOTHERAPY RESEARCH,13.
MLA Wang, Tianming,et al."Gardenia jasminoides Ellis. Polysaccharides Alleviated Cholestatic Liver Injury by Increasing the Production of Butyric Acid and FXR Activation".PHYTOTHERAPY RESEARCH (2024):13.

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来源：上海药物研究所

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