Protective effects of genistein and its glycoside sophoricoside against H2O2-induced oxidative stress in porcine enterocytes and their beneficial effect on weaned piglets

This study systematically assessed the potential beneficial effects of genistein (GEN) and its glycoside sophoricoside (SOP) on weaned piglets. To investigate the effects of GEN and SOP in alleviating oxidative damage, a cell oxidative stress model was established by exposing porcine enterocytes to hydrogen peroxide (H 2 O 2 ). Then, 100 weaned piglets were randomly allocated to four treatment groups receiving a basal diet supplemented or not with amoxicillin, GEN, or SOP for 42 days. The results showed that GEN and SOP pretreatment significantly attenuated the production of reactive oxygen species and malondialdehyde in H 2 O 2 -induced cells ( P < 0.05). Mechanistically, this protective effect was mediated via nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. Further, GEN and SOP effectively inhibited apoptosis and upregulated junction protein expression. Dietary GEN and SOP significantly increased the body weight of weaned piglets on days 14 and 42 and on day 42, respectively ( P < 0.05). GEN markedly increased catalase and total superoxide dismutase activities, whereas SOP significantly enhanced total antioxidant capacity ( P < 0.05). Both GEN and SOP modulated the intestinal microbiota composition, selectively enriching beneficial bacteria. Overall, GEN and SOP protected porcine enterocytes from H 2 O 2 -induced oxidative damage by enhancing antioxidant defenses and improving barrier function via Nrf2 signaling activation. Dietary supplementation with GEN and SOP improved growth performance, redox balance, and gut microbiota in weaned piglets, with GEN showing superior efficacy over SOP, particularly in terms of early growth performance. • Systematically assessed the beneficial effects of genistein and its glycosides sophoricoside on weaned piglets. • Genistein and sophoricoside alleviated oxidative damage to porcine enterocytes through the Nrf2 pathway. • Dietary genistein and sophoricoside improved the growth performance and intestinal microbiota composition of weaned piglets.