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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1481273
This article is part of the Research Topic Natural Products and Immune Inflammation: Mechanistic Understanding Based on Systems Biology View all 17 articles

Zhili decoction ameliorates ulcerative colitis by modulating gut microbiota and related metabolite, and inhibiting the TLR4/NF-κB/NLRP3 pathway

Provisionally accepted
Tian Ying Tan Tian Ying Tan 1Qin Chen Qin Chen 2Ping Chen Ping Chen 3*Shuangshuang Li Shuangshuang Li 1Wenting Hu Wenting Hu 1Yingtian Jia Yingtian Jia 4*Tao Yang Tao Yang 5*
  • 1 Guizhou University of Traditional Chinese Medicine, Guiyang, China
  • 2 The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, China
  • 3 Chongqing Jiangbei District Hospital of Traditional Chinese Medicine, Chongqing, China
  • 4 The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
  • 5 The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China

The final, formatted version of the article will be published soon.

    Ethnopharmacological Importance: Zhili decoction (ZLD) is a traditional Chinese medicine prescription for ulcerative colitis (UC). However, the mechanism by which ZLD exerts its therapeutic effects in the context of UC remains unclear.The aim of this study was to investigate the effects of ZLD on the gut microbiota and related fecal metabolite levels using a mouse model of UC. In addition, we examined the underlying molecular mechanisms responsible for these effects.The major components of ZLD were detected by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). An integrated approach employing 16S rRNA and fecal metabolomics was employed to assess the potential impacts of ZLD on gut flora abundance and diversity, fecal metabolite levels, and various metabolic pathways. To further investigate the potential mechanisms of ZLD in treating UC, the expression of genes and proteins were examined by RT-qPCR, immunohistochemical staining and western blotting.Results: ZLD markedly alleviated symptoms and inflammatory injury in mice with UC.DSS induced notable alterations in the gut microbiome, and ZLD enhanced gut microbial diversity in UC mice by augmenting the abundance of Bacteroidota, Christensenella, Lactobacillus, etc., while reducing the Firmicutes/Bacteroidota ratio.ZLD treatment significantly modified the metabolic profile of mice with UC. It significantly suppressed the arachidonic acid metabolic pathway and promoted the butyric acid metabolic pathway. ZLD reduced inflammatory factors and inhibited TLR4/NF-κB/NLRP3 pathway expression. In addition, correlation analysis demonstrated a close relationship between gut microbes, fecal metabolites, and inflammatory factors.Conclusions: ZLD alleviated UC by regulating gut flora, modulating related metabolite levels, and inhibiting TLR4/NF-κB/NLRP3 pathway.

    Keywords: ulcerative colitis, Zhili decoction, gut microbiome, Metabolism, TLR4/NF-κB/NLRP3 pathway

    Received: 15 Aug 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Tan, Chen, Chen, Li, Hu, Jia and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ping Chen, Chongqing Jiangbei District Hospital of Traditional Chinese Medicine, Chongqing, China
    Yingtian Jia, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
    Tao Yang, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.