The mechanism by which nonylphenol induces intestinal epithelial barrier damage and the protective effect of arabinogalactan through the PI3K/AKT/mTOR signaling pathway.

Nonylphenol (NP) is known to damage the intestinal epithelial barrier (IEB), although its mechanisms remain unclear. Arabinogalactan (AG) is a natural polysaccharide with intestinal protective properties. This study explored the mechanisms of NP-induced IEB damage and evaluated the protective potential of AG in a Caco-2 cell monolayer model. The results revealed that NP induces inflammation and oxidative stress through the PI3K/AKT/mTOR signaling pathway, thereby inhibiting tight junction (TJ) gene and protein expression and ultimately leading to IEB damage. Conversely, AG enhanced TJ expression and suppressed inflammation and oxidative stress by activating the PI3K/AKT/mTOR signaling pathway, thus alleviating NP-induced IEB damage. This research provides new insights into the molecular mechanisms of NP-induced IEB damage and highlights the potential of AG as a functional food ingredient for promoting intestinal health. Moreover, our study provides a theoretical basis for supporting policies aimed at restricting NP residues in food and offers a potential dietary reference for high-risk populations exposed to NP-contaminated environments.