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

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, H ₂ O ₂ -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 H ₂ O ₂ 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 H ₂ O ₂ -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.