Dual Immunomodulatory and Anti-Virulence Mechanisms of Curcumin Against Salmonella enterica Infection in Broilers: An Integrated Network Pharmacology and Molecular Docking Study

, a bioactive phytochemical, has shown promising antimicrobial and immunomodulatory potential; however, its precise molecular interplay with host and pathogen systems remains unclear. An integrated computational pipeline was applied, combining target prediction, host immune network construction, Salmonella virulence interaction analysis, STRING-based PPI mapping, KEGG/GO enrichment, and molecular docking validation. Host immune hub genes and Salmonella virulence regulators were identified, followed by docking of curcumin to key host (AKT1, STAT3, TNF) and pathogen proteins (invA, phoP, ssrB). Host network analysis revealed enrichment in the PI3K-AKT, NF-κB, FoxO, and IL-10 signaling pathways, indicating roles in epithelial protection, immune regulation, inflammation suppression, and antioxidant defense. Salmonella virulence hubs were primarily associated with epithelial invasion, Type III secretion, intracellular survival, and global virulence reg-ulation. Docking analysis demonstrated a strong binding affinity of curcumin toward AKT1 (-7.4 kcal/mol), STAT3 (-6.5 kcal/mol) and TNF (-5.8 kcal/mol), supporting host immunomodulation and epithelial protection. Simultaneously, curcumin showed notable affinity for phoP (-6.8 kcal/mol), invA (-6.3 kcal/mol), and ssrB (-5.8 kcal/mol), suggesting the potential suppression of virulence signaling, invasion machinery, and intracellular persistence. This integrated host-pathogen systems analysis demonstrates that curcumin exerts a dual regulatory effect by enhancing host immune protection while concurrently disrupting Salmonella virulence mechanisms. These findings provide mechanistic insight supporting curcumin as a promising natural therapeutic candidate for controlling Salmonella infection in broilers.