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Updated: May 9, 2025

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Koumine mediates the generation of mtROS through the IP3R1-GRP75-VDAC1 complex to improve Citrinin induced intestinal
Yuanyuan Li1, Xiaofang Liu1, Qike Zhang1
1Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China.
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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