A systems pharmacology-based

Introduction: Avian salmonellosis is a major bacterial disease affecting the poultry industry. With increasing restrictions on antibiotic use in animal husbandry, alternative strategies for disease prevention are urgently required. Traditional Chinese medicine, characterized by a low risk of antimicrobial resistance, represents a promising alternative for sustainable livestock production. Methods: First of all, Pulsatillae radix‌ and six additional medicinal herbs were combined to formulate Wengxian granules, and their protective effects against avian salmonellosis were assessed. Then a systems pharmacology-based method integrating main active components screening, target prediction, network analyses, GO and KEGG analyses were used for the systematic deciphering of the mechanism of Wengxian granules in avian salmonellosis. Finally, based on systems pharmacology results, molecular docking was performed using AutoDock software. Results: Following Salmonella infection, the model group exhibited increased white and red blood cell counts and a reduced lymphocyte ratio compared with the control group. Severe detachment of the cecal mucosal layer was observed in the model group. Treatment with Wengxian granules significantly reversed these alterations by decreasing white and red blood cell counts and restoring the lymphocyte ratio, and protecting the integrity of the cecal mucosa and lamina propria. Immunological analysis showed that IgM, IgG and sIgA levels were elevated in the model group after infection, whereas Wengxian granule treatment reduced these levels. At the end of the experiment, immunoglobulin levels were significantly decreased in the model group compared with controls, whereas no significant differences were observed among the Wengxian-treated groups. Network pharmacology analysis identified 40 active compounds and 66 potential therapeutic targets associated with Wengxian granules. Kaempferol, β-sitosterol, quercetin, and hesperetin were identified as key bioactive components. KEGG pathway enrichment highlighted the Toll-like and NOD-like receptor signaling pathways as major pharmacological mechanisms involved. Molecular docking further confirmed stable interactions between core targets and active compounds. Discussion: Overall, these findings indicate that Wengxian granules exert protective effects against avian salmonellosis and provide mechanistic insights into their potential application as a non-antibiotic therapeutic strategy.