Abstract: 【Objective】 The study was aimed to decipher the mechanism of mulberry leaf (ML) and Eucommia ulmoides (EU) against infectious bursal disease (IBD) based on network pharmacology, molecular docking and molecular dynamics simulations methods, and provide new insights for development of veterinary drugs against immunosuppression and IBD.【Method】 The active ingredients and the corresponding targets of ML and EU were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and SwissTargetPrediction database, and IBD-related targets were collected through GeneCards and Gene Expression Omnibus (GEO) database.Furthermore, the component-target network diagram was constructed using Cytoscape 3.7.2.Then, the intersectional targets between the active ingredients and disease were obtained and the protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape 3.7.2.Additionally, GO function and KEGG pathway enrichment were performed based DAVID database.Finally, Molecular docking was performed using AutoDock 1.5.6 and PyMOL software and molecular dynamics simulations were performed using Gromacs 2020.6 software.【Result】 A total of 53 active ingredients of ML and EU, 423 corresponding targets, 5 949 IBD-related targets and 153 common drug-disease targets were screened for analysis.PPI showed that the key targets mainly include interleukin-6 (IL6), catenin beta-1 (CTNNB1), proto-oncogene tyrosine-protein kinase Src (SRC), IL1B, vascular endothelial growth factor A (VEGFA).The results of GO function and KEGG signaling pathway showed that ML and EU exert effects against IBD through response to IL18, interferon-gamma receptor binding, neuroactive ligand-receptor interaction and calcium signaling pathway.Finally, the molecular docking and molecular dynamics simulations results showed that core active ingredients and key targets had a good binding, and bound stably.【Conclusion】 ML and EU might played a role on IL6, CTNNB1, SRC, IL1B, VEGFA and other main targets through the key active ingredients, such as quercetin, dehydrodieugenol, icosa-11, 14, 17-trienoic acid methyl ester, kaempferol and beta-sitosterol, and exert effects against infectious bursal disease through response to IL18, calcium signaling pathway and neuroactive ligand-receptor interactions.

Key words: mulberry leaf; Eucommia ulmoides; infectious bursal disease; network pharmacology; molecular docking; molecular dynamics simulation