Li Yuanyuan, Liu Xiaofang, Zhang Qike, Jiang Zonghan, Zhang Weiqing, Yang Chenglin, Ni Jie, Deng Siqi, Yi Jine, Wu Jing, Sun Zhiliang, Liang Zengenni, Yuan Zhihang
Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China.
Dongting Laboratory, Hunan Provincial Key Laboratory for Fruits and Vegetables Storage Processing and Quality Safety, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, 410125, PR China.
Phytomedicine. 2025 Jul;142:156803. doi: 10.1016/j.phymed.2025.156803. Epub 2025 Apr 25.
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.
To investigate the effect of Koumine on IBD induced by CTN exposure and its mechanism of action.
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.
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.
桔霉素（CTN）是一种难以消除且易于摄入的霉菌毒素。长期接触CTN可导致炎症性肠病（IBD）。钩吻素子具有强大的抗炎活性，被认为是治疗IBD的候选药物。
研究钩吻素子对CTN暴露诱导的IBD的影响及其作用机制。
本研究表明，钩吻素子可有效减轻CTN诱导的小鼠肠道和IPEC-J2细胞的炎症损伤。此外，钩吻素子抑制了CTN诱导的IP3R1-GRP75-VDAC1复合物上调、线粒体钙超载、线粒体活性氧（mtROS）水平升高以及随后的细胞焦亡。特异性过表达mtROS可抵消钩吻素子对CTN暴露诱导的细胞焦亡的治疗作用，但不会改变线粒体钙水平。沉默GRP75可改善CTN诱导的线粒体钙超载和细胞焦亡。值得注意的是，添加siGRP75并没有进一步增强钩吻素子的治疗效果。
钩吻素子通过IP3R1-GRP75-VDAC1复合物介导mtROS生成，从而改善CTN诱导的肠道炎症。钩吻素子是治疗CTN等霉菌毒素暴露诱导的肠道炎症的潜在药物。
