Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

文献类型: 外文期刊

第一作者: Ga, Yu

作者: Ga, Yu;Wei, Yuanyuan;Zhao, Qingyu;Fan, Yimeng;Zhang, Yannan;Hao, Zhihui;Ga, Yu;Wei, Yuanyuan;Zhao, Qingyu;Fan, Yimeng;Zhang, Yannan;Hao, Zhihui;Zhang, Zhifang;Hao, Sijia;Wang, Lixia;Wang, Zhifen;Han, Jinlong;Wu, Shuang

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关键词: Ulcerative colitis; Molecular mechanisms; Pyroptosis

期刊名称:FOOD SCIENCE AND HUMAN WELLNESS ( 影响因子:7.0; 五年影响因子:8.3 )

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年卷期: 2024 年 13 卷 4 期

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收录情况: SCI

摘要: Ulcerative colitis (UC) is a common inflammatory disease of the gastrointestinal tract. Traditional Chinese medicine (TCM) has long been used in Asia as a treatment for UC and Puerariae Radix (PR) is a reliable anti-diarrheal therapy. The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt (DSS)-induced UC model in mice and identify molecular mechanisms of PR action. The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology (NP) approach were obtained to guide mouse experiments. A total of 180 peaks were identified from PR including 48 flavonoids, 46 organic acids, 14 amino acids, 8 phenols, 8 carbohydrates, 7 alkaloids, 6 coumarins and 43 other constituents. NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC. A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice. PR also alleviated intestinal mucosal shedding, inflammatory cell infiltration and mucin loss. PR treatment suppressed upregulation of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific proteases-1 (caspase-1), apoptosis-associated speck-like (ASC) and gasdermin D (GSDMD) at both the protein and mRNA expression levels. The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR. These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice. (c) 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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