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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1513020

Polydatin protects against DSS-induced ulcerative colitis via Nrf2/Slc7a11/Gpx4-dependent inhibition of ferroptosis signalling activation

Provisionally accepted
Shimin Zheng Shimin Zheng 1Jianbin Yin Jianbin Yin 2*Bingbing Wang Bingbing Wang 1*Qiujuan Ye Qiujuan Ye 3*Jialuo Huang Jialuo Huang 2*Junfeng Wu Junfeng Wu 2*Xinzhi Liang Xinzhi Liang 2Hui Yue Hui Yue 1*Ting Zhang Ting Zhang 1*
  • 1 Department of Gastroenterology,The Third Affiliated Hospital，Southern Medical University, Guangzhou, China, Guangzhou, China
  • 2 Department of Orthopedics, Third Affiliated Hospital, Southern Medical University, Guangzhou, China
  • 3 Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China

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

    Ulcerative colitis (UC), a form of inflammatory bowel disease, is characterized by a recurrent and persistent nonspecific inflammatory response. Polydatin (PD), a natural stilbenoid polyphenol with potent properties, exhibits unexpected beneficial effects beyond its welldocumented anti-inflammatory and antioxidant activities. In this study, we presented evidence that PD confers protection against dextran sodium sulfate (DSS)-induced ulcerative colitis. Our findings demonstrated that PD mitigated the DSS-induced increases in proinflammatory cytokines (IL-6, TNF-α, and IL-1β), alleviated colon length shortening, reduced morphological damage to the intestinal mucosa, and preserved tight junction proteins (TJ) occludin and Zonula occludens-1 (ZO-1) in both Caco-2 cells and murine models of colitis. Results from bulk RNA sequencing and differential gene analysis suggested a potential role for ferroptosis in the protective mechanisms of PD against UC. Further investigations revealed that PD modulated the expression levels of several ferroptosis-related proteins and transcription factors within the DSS-induced colitis model. Notably, treatment with PD enhanced nuclear translocation of Nrf2, which inhibits ferroptosis while ameliorating oxidative stress through upregulation of Slc7a11 and Gpx4 expression. Additionally, erastina known inducer of ferroptosis-reversed the protective effects conferred by PD in the DSSinduced colitis model by downregulating Slc7a11 expression. These findings underscore that PD protects against DSS-induced ulcerative colitis via the Nrf2/Slc7a11/Gpx4 signaling axis, highlighting its potential as a novel therapeutic agent for UC.

    Keywords: Polydatin, DSS-induced ulcerative colitis, ferroptosis, Nrf2, SLC7A11, GPx4

    Received: 17 Oct 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Zheng, Yin, Wang, Ye, Huang, Wu, Liang, Yue and Zhang. 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:
    Jianbin Yin, Department of Orthopedics, Third Affiliated Hospital, Southern Medical University, Guangzhou, China
    Bingbing Wang, Department of Gastroenterology,The Third Affiliated Hospital，Southern Medical University, Guangzhou, China, Guangzhou, China
    Qiujuan Ye, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
    Jialuo Huang, Department of Orthopedics, Third Affiliated Hospital, Southern Medical University, Guangzhou, China
    Junfeng Wu, Department of Orthopedics, Third Affiliated Hospital, Southern Medical University, Guangzhou, China
    Hui Yue, Department of Gastroenterology,The Third Affiliated Hospital，Southern Medical University, Guangzhou, China, Guangzhou, China
    Ting Zhang, Department of Gastroenterology,The Third Affiliated Hospital，Southern Medical University, Guangzhou, China, Guangzhou, China

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