Resveratrol ameliorates Salmonella Typhimurium-induced intestinal inflammation and barrier dysfunction in chickens via COX-2 inhibition

Salmonella enterica subsp. enterica serovar Typhimurium (Salmonella Typhimurium) is a prominent foodborne pathogen that elicits considerable morbidity and mortality in poultry. This study explored the potential of resveratrol (RES) as a treatment for S. Typhimurium infection, focusing on its effects in Wenchang chickens. We tested three doses of RES (50, 100, and 200 mg/kg body weight) to assess its impact on inflammatory cytokine levels, intestinal barrier function, growth performance, and clinical signs in infected chickens. In the group treated with 200 mg/kg of RES, we observed a marked improvement in feed conversion ratio (FCR) and average daily gain (ADG) between days 7 and 14 post-infection. Both the 100 mg/kg and 200 mg/kg doses helped restore the intestinal barrier, reversing the damage caused by S. Typhimurium and normalizing the villus height-to-crypt depth (VH:CD) ratio in the jejunum. Additionally, the 200 mg/kg group showed enhanced repair of the intestinal barrier, with a significant reduction in the expression of pro-inflammatory cytokines (IL-6, TNF-α, TGF-β) and an increase in the levels of tight junction proteins (ZO-1, Occludin, Claudin-1). RES decreased COX-2 mRNA expression in intestinal epithelial cells, thereby reducing the activation of prostaglandin-related inflammatory pathways. In vitro experiments using S. Typhimurium-infected HD11 macrophages showed that RES inhibited both COX-2 enzymatic activity and the release of inflammatory cytokines (TNF-α, IL-1β, IL-6, and TGF-β) in a dose-dependent manner. In conclusion, these results highlight RES as a promising natural treatment for S. Typhimurium infection in poultry.