Hyperoside Derived from Actinidia arguta Bee Pollen Alleviates Zearalenone-Induced Hepatotoxicity and Oxidative Stress in Piglets via the PI3K/AKT Signaling Pathway

Abstract Zearalenone (ZEA) is a prevalent mycotoxin inducing hepatotoxic effects. Hyperoside (HYP), a flavonoid derived from Actinidia arguta bee pollen, exhibits hepatoprotective properties against ZEA; however, the molecular mechanisms underlying this protection remain incompletely characterized. This study integrated in vivo piglet models, in vitro porcine hepatocytes, network pharmacology, and molecular docking to characterize the molecular targets of HYP. The results demonstrated that HYP significantly attenuated ZEA-induced hepatic lesions and oxidative stress. Computational analyses pinpointed the PI3K/AKT signaling pathway as the core target of HYP. In vitro validation revealed that HYP phenocopied the AKT activator SC79 in suppressing ZEA-induced hepatocyte apoptosis, an efficacy partially abrogated by the PI3K inhibitor LY294002. Conclusively, HYP ameliorates ZEA-induced hepatotoxicity by activating the PI3K/AKT axis to mitigate oxidative stress and apoptosis, underscoring its translational potential as a functional detoxifying additive for food and feed applications.