Curcumin Activates the Wnt/β-Catenin/PPARD Signaling Axis to Attenuate Ochratoxin A‑Induced Enterotoxicity

Ochratoxin A (OTA), a widespread and highly toxic pollutant, frequently contaminates animal feed and poses a significant threat to human and animal health. Curcumin (CUR), a natural polyphenol with well-characterized anti-inflammatory and antioxidant chemical properties, holds promise for mycotoxin mitigation. However, the function and molecular mechanism of CUR in alleviating OTA-induced intestinal injury remain largely unknown. In this work, we explored the alleviating effect and molecular mechanism of CUR on OTA enterotoxicity by integrating in vitro and in vivo models with transcriptomic techniques and experimental validation. We first confirmed that CUR significantly ameliorated OTA-induced intestinal barrier injury and oxidative stress in porcine intestinal epithelial (IPEC-J2) cells. Transcriptomic sequencing revealed that activation of the Wnt/β-catenin/PPARD signaling axis was the key pathway mediating CUR’s protective effects, representing a novel chemical–biological cross-talk. Mechanistic studies demonstrated that CUR specifically enhanced β-catenin nuclear translocation and upregulated PPARD expression to remodel cellular signaling networks, with these protective effects being markedly attenuated upon PPARD gene perturbation. Animal experiments further validated that CUR intervention significantly alleviated OTA-induced intestinal villus atrophy in mice, while improving intestinal oxidative stress and restoring structural integrity. This study elucidates a novel molecular mechanism by which CUR mitigates OTA-induced intestinal toxicity through targeted chemical modulation of the Wnt/β-catenin/PPARD signaling axis, demonstrating its potential as a chemically safe and mechanism-based additive and providing an innovative intervention strategy to address mycotoxin contamination challenges.