Piceatannol, a natural stilbene, improves weaning piglets' growth performance through the regulation of Nrf2-mediated redox homeostasis and modulation of the related gut microbiota

Abstract Background Piglets are highly susceptible to oxidative stress, which can reduce growth performance and cause intestinal damage. Piceatannol (PIC), a natural bioactive substance enriched in Chinese rhubarb (Rheum officinale) and certain dark purple fruits, shows excellent antioxidant properties in our previous cell-based high-throughput screening. However, its effect on piglet growth performance and antioxidant capacity as well as underling mechanism has not been thoroughly investigated. Methods One hundred weaned pigs (28 d of age, 8.71 ± 0.20 kg) were randomly assigned to 4 treatments with 5 replicates of 5 pigs per replicate. The experimental diets consisted of: 1) basal diet, 2) basal diet + 100 mg/kg PIC, 3) basal diet + 200 mg/kg PIC, and 4) basal diet + 300 mg/kg PIC. On d 15 and 35, one pig from each replicate was selected for sampling. The growth performance was monitored during a 35-day trial. In addition, H₂O₂-challenged IPEC-J2 cells served as an in vitro model to investigate the antioxidant mechanisms of PIC. IPEC-J2 cells were treated with 1,000 µM H₂O₂ in the presence or absence of 10 µM PIC. Results Dietary PIC at 200 mg/kg significantly enhanced growth performance, as evidenced by increased average daily gain and feed conversion rate (P < 0.05). PIC supplementation markedly improved systemic antioxidant capacity, with elevated serum total antioxidant capacity, catalase activity, and glutathione levels, along with reduced malondialdehyde content (P < 0.05; P < 0.01). Notably, PIC modulated the gut microbiota composition, increasing the amounts of beneficial genera (e.g., Blautia and Faecalibacterium), and these microbial shifts significantly correlated with improved antioxidant indices. In vitro, PIC pretreatment effectively protected IPEC-J2 cells against H₂O₂-induced oxidative damage by reducing reactive oxygen species generation and lipid peroxidation (P < 0.01). Mechanistically, PIC exerts its antioxidant effects through Nrf2 pathway activation, upregulating endogenous antioxidant enzymes (P < 0.05; P < 0.01) while simultaneously inhibiting apoptosis via the regulation of the Bcl-2/Bax ratio and caspase-3 cleavage (P < 0.01). Conclusions PIC improved the growth performance and health status of weaned piglets through the regulation of Nrf2-mediated redox homeostasis and modulation of the related gut microbiota, offering a potential new natural antioxidants for mitigating weaning stress in piglets.