Abstract
Salmonella is a major zoonotic pathogen and a leading cause of foodborne illness worldwide, posing serious threats to public health and livestock production. The rapid emergence of multidrug-resistant strains underscores the urgent need for alternative anti-infective strategies. Antivirulence therapies targeting pathogen virulence factors (e.g., the type III secretion system 1, T3SS-1) have gained increasing attention because they mitigate infection and minimize resistance development. Here, we systematically evaluated the protective efficacy of Houttuynia cordata extract (HCE) in both murine and economically relevant chick infection models of Salmonella Typhimurium and Salmonella Pullorum. HCE significantly improved host pathology, alleviated intestinal barrier damage, reduced bacterial burden in target organs and modulated inflammatory responses. Mechanistically, HCE downregulated HilA, the central transcriptional regulator of T3SS-1, thereby suppressing effector protein secretion and bacterial invasion. These findings provide robust in vivo evidence supporting HCE as a low-cost, natural antivirulence candidate for the prevention and control of Salmonella infections in the poultry farming industry.