Magnolol Improves Intestinal Antioxidant Capacity and Barrier Function by Activating the Nrf2 Signaling Pathway in a Piglet Model

ABSTRACT Magnolol is a natural bioactive phenolic compound with potent antioxidant properties and plays an important role in modulating intestinal healthy. However, the underlying mechanisms of magnolol in alleviating intestinal oxidative stress damage and improving the intestinal barrier integrity remain unknown. Thus, this study aimed to evaluate the effects of magnolol on intestinal antioxidant capacity and barrier function in weaned piglets and 2,2′‐azobis (2‐methylpropionamidine) dihydrochloride (AAPH) challenged IPEC‐J2 cell models. The results showed that magnolol supplementation significantly increased ( p < 0.05) serum T‐AOC, jejunal mucosa T‐SOD and GSH‐PX, and ileal mucosa T‐SOD activities in weaned piglets. Magnolol also upregulated ( p < 0.05) the mRNA expression of antioxidant enzymes ( SOD1 , CAT , GCLM , and GR ) in the small intestine, while decreased ( p < 0.05) the MDA level in both serum and jejunum. Meanwhile, magnolol improved intestinal barrier function, as evidenced by reduced ( p < 0.05) serum diamine oxidase activity, D‐lactate acid, and endotoxin levels, while increased ( p < 0.05) villus height and jejunal and ileal protein expression of tight junction proteins (ZO‐1, occludin, and claudin‐1). It further downregulated ( p < 0.05) the proapoptosis protein (caspase‐9, caspase‐3, and Bax) and upregulated antiapoptosis protein Bcl2. In vitro studies further revealed that magnolol pretreatment effectively alleviated ( p < 0.05) AAPH‐induced oxidative stress, barrier dysfunction, and apoptosis by activating the key proteins expression in Nrf2 signaling pathway in IPEC‐J2 cells. These findings indicated that magnolol enhances intestinal antioxidant capacity and exerts antiapoptotic effects, while preserving epithelial barrier integrity, potentially via activation of the Nrf2 signaling pathway.