Tianming Wang, Tian Tian, Zhenyun Zhu, Su Fang, Lincong Zhang, Xiaotian Peng, Rong Shi, Yuanyuan Li, Jiasheng Wu, Yueming Ma
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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<sup>+</sup> and Ly6G<sup>+</sup> 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-κB) 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-κB inflammatory pathway, exerting protective effects against CLI.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Gardenia jasminoides Ellis. 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引用次数: 0
摘要
栀子多糖(GPS)可通过调节核法尼类固醇 X 受体(FXR)防止胆汁淤积性肝损伤(CLI)。本研究旨在探究其机制。首先,给α-萘基硫氰酸盐诱导的胆汁淤积小鼠模型注射GPS,以评估其保肝作用。血清代谢组学检测了GPS对胆汁淤积症小鼠代谢途径的影响。研究了GPS对胆汁酸(BA)稳态、FXR表达和肝脏炎症的影响。其次,测定了体内和体外受 GPS 影响的肠道细菌代谢物。测量了丁酸钠(NaB)对 FXR 的激活作用。最后,证明了 NaB 对胆汁淤积性小鼠的影响。受 GPS 影响的主要途径涉及 BA 的生物合成。GPS 上调肝脏 FXR 的表达,改善 BA 的平衡,减少肝脏中 F4/80+ 和 Ly6G+ 阳性区域,并抑制胆汁淤积性小鼠的肝脏炎症。丁酸是 GPS 干预后最显著的肠道细菌代谢产物。NaB 在体外激活了 FXR 的转录活性,上调了肝脏 FXR 及其下游外排转运体的表达,并改善了 CLI 小鼠体内紊乱的 BA 平衡。NaB 可抑制收费样受体 4/核因子(TLR4/NF-κB)通路,减轻小鼠的炎症和 CLI。FXR拮抗剂抑制了这种效应。总之,GPS能增加丁酸的产生,从而激活肝脏FXR,逆转BA平衡失调,抑制TLR4/NF-κB炎症通路,对CLI具有保护作用。
Gardenia jasminoides Ellis. Polysaccharides Alleviated Cholestatic Liver Injury by Increasing the Production of Butyric Acid and FXR Activation.
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-κB) 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-κB inflammatory pathway, exerting protective effects against CLI.
期刊介绍:
Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field.
Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters.
By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.