Dietary esculetin improves growth performance and spleen function via the NF-κB/MAPK pathway in heat-stressed broilers

This study evaluated the effects of esculetin on heat stress-induced splenic immunosuppression in broilers. Esculetin significantly reduced rectal temperature and respiratory rate in heat-stressed broilers ( P < 0.05), improved growth performance, serum biochemical parameters, and the spleen index, and attenuated heat stress-induced splenic histopathological damage and HSP70 expression. Concurrently, esculetin elevated serum levels of immunoglobulins (IgA, IgM, and IgG) and upregulated the gene expression of anti-inflammatory cytokines, while downregulating pro-inflammatory cytokine genes (IL-1β, IL-6, and TNF-α). Network pharmacology analysis, molecular docking, and in vivo validation demonstrated that the immunomodulatory effects of esculetin were primarily mediated through targeting NF-κB, TNF-α, and IL-6, thereby modulating the NF-κB/MAPK signaling pathway. These findings provide a scientific basis for the application of esculetin as a functional feed additive to alleviate heat stress-induced immune dysfunction in poultry.