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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1495799
This article is part of the Research Topic Prevention and Treatment of Metabolic Diseases Using Bioactive Metabolites of Herbal Medicines Also Used as Foods View all 4 articles

Network analysis and experimental validation to investigate the Chenpi against functional dyspepsia through TLR4/MyD88 by regulating gut microbial structure

Provisionally accepted
Jinfang Hu Jinfang Hu 1,2Xu Wang Xu Wang 3Xiaoqiu Guo Xiaoqiu Guo 4Wen Wen Wen Wen 5Zhengzheng Liao Zhengzheng Liao 2,6*Lihua Chen Lihua Chen 1
  • 1 Key Laboratory of Modern Preparation of Traditional Chinese Medicines, Ministry of Education, Jiangxi University of Chinese Medicine, 330004, Nanchang, China, Nanchang, China
  • 2 Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
  • 3 Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China., Nanchang, China
  • 4 Department of Pharmacy, the Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi, P.R.China, Nanchang, China
  • 5 Jiangxi Center for Drug Certification and Evaluation, Nanchang Jiangxi 330029, China, Nanchang, China
  • 6 State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology, Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University., Nanchang, China

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

    Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder characterized by the absence of organic lesions, affecting nearly one-fifth of the global population. However, there is currently no specific drug for treating FD. Citri Reticulatae Pericarpium (CRP) has been utilized in China for millennia as a therapeutic agent for alleviating bloating and spleen-stomach disharmony. Nonetheless, the curative efficacy and the precise molecular mechanisms implicated in FD warrant further elucidation. This study aims to address this gap by investigating the potential mechanisms of CRP against FD using HPLC-ESI-QTOF-MS, network analysis prediction, and experimental validation. In present study, 90 metabolites in CRP were identified by HPLC-ESI-QTOF-MS. 70 common targets of CRP and FD were extracted, and the top 10 overlapped targets included MAPK1, MAPK2 and MAPK3. KEGG enrichment analysis revealed that the MAPK pathways were predominant and involved the TLR4 signaling pathway. In vivo experiments demonstrated that after 14 days of treatment, CRP improved body weight, gastric emptying rate, intestinal transit rate, and the pathological structure of gastric tissue. Serum IL-6, TNF-α, and IL-1β were downregulated, and the expression of TLR4, MyD88, p-NF-κB, and MAPKs were suppressed in gastric tissue. Besides, CRP increased the relative abundance of Patescibateria and Bacteroidota, accompanied by reduction in relative abundance of Verrucomicrobota and Proteobacteria. In brief, CRP could attenuate dyspepsia by reducing the activation of inflammation-related TLR4/MyD88 and MAPKs signaling pathways and mediating gut microbial structure and composition. This study provides a unique perspective for further research on FD treatment drugs.

    Keywords: functional dyspepsia, Citri Reticulatae Pericarpium, Inflammation, TLR4/MyD88, Gut microbe

    Received: 13 Sep 2024; Accepted: 03 Jan 2025.

    Copyright: © 2025 Hu, Wang, Guo, Wen, Liao and Chen. 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: Zhengzheng Liao, Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 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.