ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1629012
This article is part of the Research TopicAdvances in the Treatment of Acute Severe Ulcerative ColitisView all 4 articles
Mechanistic Study on the Restoration of Intestinal Barrier Integrity and Alleviation of Inflammatory Bowel Disease by Rhynchophylline via the AhR-NR4A1 Pathway
Provisionally accepted
- 1Xinjiang Medical University, Ürümqi, China
- 2Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, China
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Restoring intestinal barrier function is considered an effective strategy for the treatment of Inflammatory Bowel Disease (IBD). Rhynchophylline (Rhy), a bioactive alkaloid sourced from the traditional herbs Uncariarhynchophylla used in Chinese medicine, is known for its antihypertensive, anti-asthmatic, and antitumor properties. This study explores the pharmacological effects and molecular mechanisms of Rhy in treating IBD. In vitro results indicate that the levels of inflammatory markers-including IL-6, TNF-α, and NO-can be decreased by Rhy, demonstrating anti-inflammatory activity. It significantly lowers intestinal epithelial permeability, promotes the proliferation of intestinal epithelial cells, and upregulates the expression of tight junction proteins Claudin4, Occludin, and ZO-1. These effects improve cellular morphology and improve the robustness of the intestinal barrier. In vivo, using three types of colitis animal models, Rhy shows significant protective effects on mice with acute and chronic colitis. It markedly reduces weight loss and Disease Activity Index (DAI) scores, prevents colonic shortening, reduces intestinal permeability, and decreases serum levels of IL-6, TNF-α, CXCL1, and IL-1β. These effects restore the structural integrity of colonic tissues and alleviate symptoms of acute and chronic colitis. Additionally, using transcriptomics, gene knockout techniques, and molecular dynamics simulations, we found that Rhy activates the AhR-NR4A1 pathway. This activation upregulates Claudin4, Occludin, and ZO-1 to repair the intestinal barrier and exert anticolitic effects. These findings highlight Rhy improve the function of function and inhibits inflammation, providing dual beneficial activities in the epithelial lining of the gut to prevent and treat colitis.
Keywords: Rhynchophylline, Inflammatory Bowel Diseases, intestinal barrier integrity, AhR, Nr4a1
Received: 15 May 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Mao, Cheng, Liu and Wu. 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: Lufeng Cheng, Xinjiang Medical University, Ürümqi, China
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