Abstract: 【Objective】 This study was conducted to reveal the mechanism of Lianshenzhilikeli in the treatment of swine diarrhea by network pharmacology and molecular docking.【Method】 Traditional Chinese Medicine Systems Pharmacology Database and Analysis platform (TCMSP) and Encyclopedia of Traditional Chinese Medicine (ETCM) platform were used to search for the active ingredients and targets of Coptidis Rhizoma, Pulsatilliae Radix, Sophorae flavescentis Radix, Chebulae fructus and licorice in Lianshenzhilikeli, and the network diagram of active ingredients and their targets was constructed by the Cytoscape 3.7.2 software.Swine diarrhea disease targets were obtained from NCBI, OMIM, GeneCards and MalaCards platform.The intersections of disease and ingredient targets were uploaded to the STRING 11.5 database, and the protein-protein interaction (PPI) network diagram was built by the Cytoscape 3.7.2 software.The GO function and KEGG signal pathway enrichment of the core targets in the PPI network were analyzed via microscopic letter platform.The key active ingredients and the core targets were verified by molecular docking technology.【Result】 96 active ingredients of Lianshenzhilikeli, 208 drug targets and 1 785 disease targets were obtained after screening.PPI analysis showed that the key targets of Lianshenzhilikeli directly targeting to swine diarrhea disease were Jun proto-oncogene (JUN), mitogen-activated protein kinase 14 (MAPK14), MYC proto-oncogene (MYC), NFKB inhibitor alpha (NFKBIA), NF-κB p65 (RELA), caspase-3 (CASP3), tumor necrosis factor (TNF), MAPK1, interleukin 6 (IL6), estrogen receptor 1 (ESR1) and so on.Six items of biological process, two items of cellular component and two items of molecular function were obtained from GO function screening.Biological processes included positive regulation of transcription from RNA polymerase Ⅱ promoter, positive regulation of interleukin-8 production, positive regulation of sequence-specific DNA binding transcription factor activity, cellular response to lipopolysaccharide, negative regulation of apoptotic process and regulation of transcription from RNA polymerase Ⅱ promoter.Cellular components included nucleus and cytoplasm.Molecular functions included RNA polymerase Ⅱ core promoter proximal region sequence-specific DNA binding and DNA binding.A total of 53 signal pathways were obtained from KEGG pathway enrichment analysis, and two of them closely were relating to the disease.The results of molecular docking showed that the key active ingredients of Lianshenzhilikeli had excellent binding activity to the swine diarrhea disease targets.【Conclusion】 Lianshenzhilikeli might regulate Salmonella infection disease pathway and IL17 signaling pathway by targeting to JUN, RELA, MYC, NFKBIA, MAPK14, CASP3, TNF, MAPK1 and IL6 through the active ingredients, such as formononetin, 3', 7-dihydroxy-4', 6-dimethoxyisoflavone, 3, 3'-dimethylquercetin, pinocembrin, (R)-(6-methoxy-4-quinolyl)-[(2R, 4R, 5S)-5-vinylquinuclidin-2-yl]methanol, inermine, 1-methoxyphaseollidin, 2, 4, 4'-trihydroxychalcone, so as to achieve the purpose of treating the disease.

Key words: Lianshenzhilikeli; swine diarrhea; network pharmacology; molecular docking; mechanism