Exploring the mechanism of ursolic acid in preventing liver fibrosis and improving intestinal microbiota based on NOX2/NLRP3 inflammasome signaling pathway.

Qi Liu, Lin-Xiang Liu, Bi-Min Li, Wang Zhang, Yue Zhang, Peng Chen, Chen-Kai Huang, Yuan Nie, Xuan Zhu
{"title":"Exploring the mechanism of ursolic acid in preventing liver fibrosis and improving intestinal microbiota based on NOX2/NLRP3 inflammasome signaling pathway.","authors":"Qi Liu, Lin-Xiang Liu, Bi-Min Li, Wang Zhang, Yue Zhang, Peng Chen, Chen-Kai Huang, Yuan Nie, Xuan Zhu","doi":"10.1016/j.cbi.2024.111305","DOIUrl":null,"url":null,"abstract":"<p><p>Early-stage liver fibrosis can be reversed; however, the underlying mechanisms remain incompletely understood. The intestinal tract hosts a substantial and diverse microbiota involved in various physiological activities and is closely linked to chronic liver disease. Previous studies have indicated that ursolic acid (UA), derived from herbal plants, possesses anti-inflammatory and antifibrotic properties; however, its precise mechanism remains to be elucidated. Consequently, liver fibrosis models were constructed utilizing both the methionine/choline deficieny (MCD) diet and carbon tetrachloride (CCl4) intraperitoneal injections. 16S rRNA was conducted to analyze the intestinal microbiota. Results indicated that UA attenuated liver injury and fibrosis, reduced indices related to liver fibrosis, and decreased the expression levels of NADPH oxidase 2 (NOX2) and NOD like receptor protein 3 (NLRP3). Hepatic fibrosis was alleviated in post-model NOX2 and NLRP3 gene knockout (NOX2<sup>-/-</sup> and NLRP3<sup>-/-</sup>) mice in comparison to post-model wild-type (WT) mice. Nonetheless, neither UA treatment nor control treatment significantly improved liver fibrosis in comparison to post-model knockout mice. Furthermore, the liver of NOX2<sup>-/-</sup> mice exhibited lower levels of NLRP3 expression. Importantly, knockout mice displayed a higher diversity of intestinal microbiota, characterized by an increased presence of beneficial bacteria and a reduced presence of harmful bacteria compared to WT mice. In conclusion, UA exerts antifibrotic effects through the inhibition of the NOX2/NLRP3 inflammasome signaling pathway. UA has the potential to reverse liver fibrosis by modulating this signaling pathway, thereby enhancing the gut microbiota.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemico-biological interactions","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.cbi.2024.111305","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Early-stage liver fibrosis can be reversed; however, the underlying mechanisms remain incompletely understood. The intestinal tract hosts a substantial and diverse microbiota involved in various physiological activities and is closely linked to chronic liver disease. Previous studies have indicated that ursolic acid (UA), derived from herbal plants, possesses anti-inflammatory and antifibrotic properties; however, its precise mechanism remains to be elucidated. Consequently, liver fibrosis models were constructed utilizing both the methionine/choline deficieny (MCD) diet and carbon tetrachloride (CCl4) intraperitoneal injections. 16S rRNA was conducted to analyze the intestinal microbiota. Results indicated that UA attenuated liver injury and fibrosis, reduced indices related to liver fibrosis, and decreased the expression levels of NADPH oxidase 2 (NOX2) and NOD like receptor protein 3 (NLRP3). Hepatic fibrosis was alleviated in post-model NOX2 and NLRP3 gene knockout (NOX2-/- and NLRP3-/-) mice in comparison to post-model wild-type (WT) mice. Nonetheless, neither UA treatment nor control treatment significantly improved liver fibrosis in comparison to post-model knockout mice. Furthermore, the liver of NOX2-/- mice exhibited lower levels of NLRP3 expression. Importantly, knockout mice displayed a higher diversity of intestinal microbiota, characterized by an increased presence of beneficial bacteria and a reduced presence of harmful bacteria compared to WT mice. In conclusion, UA exerts antifibrotic effects through the inhibition of the NOX2/NLRP3 inflammasome signaling pathway. UA has the potential to reverse liver fibrosis by modulating this signaling pathway, thereby enhancing the gut microbiota.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
基于NOX2/NLRP3炎性体信号通路探索熊果酸预防肝纤维化和改善肠道微生物群的机制
早期阶段的肝纤维化是可以逆转的;然而,人们对其基本机制仍不完全了解。肠道内有大量多样的微生物群,参与各种生理活动,与慢性肝病密切相关。以往的研究表明,从草本植物中提取的熊果酸(UA)具有抗炎和抗肝纤维化的特性,但其确切机制仍有待阐明。因此,利用蛋氨酸/胆碱缺乏(MCD)饮食和腹腔注射四氯化碳(CCl4)构建了肝纤维化模型。16S rRNA用于分析肠道微生物群。结果表明,UA减轻了肝损伤和肝纤维化,降低了与肝纤维化相关的指数,并降低了NADPH氧化酶2(NOX2)和NOD样受体蛋白3(NLRP3)的表达水平。与建模后的野生型(WT)小鼠相比,NOX2 和 NLRP3 基因敲除(NOX2-/- 和 NLRP3-/-)小鼠的肝纤维化有所缓解。然而,与模型敲除后的小鼠相比,UA 治疗和对照组治疗都不能明显改善肝纤维化。此外,NOX2-/-小鼠肝脏中的NLRP3表达水平较低。重要的是,与 WT 小鼠相比,基因敲除小鼠显示出更高的肠道微生物群多样性,其特点是有益菌增多,有害菌减少。总之,UA通过抑制NOX2/NLRP3炎性体信号通路发挥抗肝纤维化作用。通过调节这一信号通路,UA 有可能逆转肝纤维化,从而增强肠道微生物群。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Exploring the mechanism of ursolic acid in preventing liver fibrosis and improving intestinal microbiota based on NOX2/NLRP3 inflammasome signaling pathway. Multiomic analysis of Lewisite exposed human dermal equivalent tissues. Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease. Elucidating the Molecular Mechanisms of Pterostilbene Against Cervical Cancer Through an Integrated Bioinformatics and Network Pharmacology Approach Neurotoxicity of Pyrethroids in exacerbating neurodegenerative diseases: From animals' models to humans’ studies
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1