Koumine mediates the generation of mtROS through the IP3R1-GRP75-VDAC1 complex to improve Citrinin induced intestinal inflammation

文献类型： 外文期刊

第一作者： Li, Yuanyuan

作者： Li, Yuanyuan;Liu, Xiaofang;Zhang, Qike;Jiang, Zonghan;Yang, Chenglin;Ni, Jie;Deng, Siqi;Yi, Jine;Wu, Jing;Sun, Zhiliang;Yuan, Zhihang;Zhang, Weiqing;Liang, Zengenni;Liang, Zengenni

作者机构：

关键词： Koumine; Citrinin; Inflammatory bowel disease; Pyroptosis

期刊名称：PHYTOMEDICINE （ 影响因子：8.3； 五年影响因子：8.0 ）

ISSN： 0944-7113

年卷期： 2025 年 142 卷

页码：

收录情况： SCI

摘要： Background: Citrinin (CTN) is a mycotoxin that is difficult to eliminate and easy to ingest. Chronic exposure to CTN can lead to inflammatory bowel disease (IBD). The herb Koumine has strong anti-inflammatory activity and is considered a candidate for the treatment of IBD. Purpose: To investigate the effect of Koumine on IBD induced by CTN exposure and its mechanism of action. Results: This study demonstrated that Koumine effectively attenuates CTN-induced inflammatory damage in the mouse intestine and IPEC-J2 cells. Furthermore, Koumine suppressed CTN-induced upregulation of the IP3R1-GRP75-VDAC1 complex, mitochondrial calcium overload, elevated mitochondrial reactive oxygen species (mtROS) levels, and subsequent pyroptosis. Specific overexpression of mtROS counteracted the therapeutic effect of Koumine on CTN exposure-induced pyroptosis but did not alter mitochondrial calcium levels. Silencing GRP75 ameliorated CTN-induced mitochondrial calcium overload and pyroptosis. Notably, siGRP75 addition did not further enhance the therapeutic effect of Koumine. Conclusions: Koumine ameliorates CTN-induced intestinal inflammation by mediating mtROS production via the IP3R1-GRP75-VDAC1 complex. Koumine is a potential agent for the treatment of intestinal inflammation induced by mycotoxin exposure such as CTN.

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