Curcumin alleviates DON-induced intestinal epithelial barrier disruption. - GreenMedInfo Summary

Deoxynivalenol (DON) is a pervasive ribotoxic stressor that induces intestinal epithelial barrier disruption by impairing tight junctions (TJs) and causing cellular damage. Curcumin (CUR), known for its enteroprotective properties and low toxicity, has been shown to attenuate DON-induced intestinal epithelial barrier injury. However, the underlying mechanisms are still unclear. In this study, we established in vivo and in vitro models using 30 male Kunming mice and IPEC-J2 cells to investigate the mechanisms by which CUR alleviates DON-induced intestinal epithelial barrier injury. The results showed that CUR markedly reduced DON-induced increases in intestinal permeability by restoring TJ protein expression (Claudin-4 and occludin) and preventing fiber-shaped actin (F-actin) contraction. CUR also attenuated DON-induced apoptosis by downregulating p53 and caspase activation and alleviated the G1 cell cycle arrest by reducing p21 expression. Mechanistically, CUR inhibited the activation of the ribosomal stress response (RSR)-associated p38 pathway, evidenced by decreased phosphorylation of p38, GSK3β, and ATF-2. The p38 activator dehydrocorydaline reversed CUR's protective effects. In conclusion, CUR alleviates DON-induced intestinal epithelial barrier disruption by improving RSR-associated p38 pathway-mediated TJ injury, apoptosis, and cell cycle arrest. These findings highlight the potential of CUR as a therapeutic agent for mitigating mycotoxin-induced intestinal dysfunction and suggest new avenues for drug target discovery.