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.