Caffeic acid improves intestinal barrier function integrity through activation of Nrf2 signaling pathway in weaned...

Caffeic acid (CA), a common plant polyphenol, is considered to be a potentially powerful antioxidant and plays an important role in regulating intestinal barrier function. However, the underlying mechanism of CA in improving the intestinal barrier integrity and alleviating intestinal oxidative stress damage remains unclear. The aim was to study the effects of CA on the intestinal barrier function integrity of weaned piglets and hydrogen peroxide (H₂O₂) induced porcine intestinal epithelial cells (IPEC-J2 cells), and further explore its possible mechanism. The results of in vivo experiments showed that CA could significantly improve the growth performance and intestinal antioxidant capacity of piglets, improve the integrity of the jejunal mucosa, and reduce the incidence of diarrhea. The results of in vitro experiments showed that CA treatment effectively alleviated H₂O₂ induced oxidative stress in IPEC-J2 cells and increased the expression of key molecules in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. In addition, CA reduced the H₂O₂-induced increase of lactate dehydrogenase (LDH) release, and reversed the inhibition of H₂O₂ on tight junction related-proteins expressions and cell migration and increase in epithelial permeability in IPEC-J2 cells. However, the addition of Nrf2-specific inhibitor ML385 reversed the effect of CA. Taken together, CA could improve intestinal barrier integrity in weaned piglets, and it could alleviate H₂O₂-induced intestinal epithelial cell damage by activating Nrf2 signaling pathway.