关键词: 锦灯笼提取物; 传染性支气管炎; 网络药理学; UPLC-Q-TOF-MS

Abstract: 【Objective】 Based on UPLC-Q-TOF-MS technology,global natural products social molecular networking system (GNPS) and network pharmacology,the mechanism of action of extract of Physalis Calyx seu Fructus on infectious bronchitis (IB) was explored to provide theoretical basis for the treatment of IB.【Method】 The chemical ingredients in extract of Physalis Calyx seu Fructus were analyzed by UPLC-Q-TOF-MS and GNPS,and the active ingredients and the targets were screened by oral bioavailability ≥30% and drug-like properties ≥0.18 matching with TCMSPS and SwissTargetPrediction databases,and then intersection targets with IB were performed.The interaction network diagram between extract of Physalis Calyx seu Fructus and the disease targets was drawn, the degree value of each node was analyzed by using the CytoNCA plug-in in Cytoscape 3.10.1,the core protein-protein interaction (PPI) network and the active ingredient target network were constructed by using the intersecting targets,and the key targets were analyzed in terms of GO function and KEGG pathway enrichment. AutoDock Vina was used for molecular docking validation.【Result】 Ten substances were analyzed in UPLC-Q-TOF-MS in negative ion mode,and 32 substances were analyzed in positive ion mode.Luteolin and kaempferol-7-O-glucoside could be detected in both positive and negative ion modes.Among them,18 compounds met the conditions required for network pharmacology,and there were 145 intersecting targets between the action targets of these compounds and the disease targets related to IB.Based on the intersecting targets,network pharmacological analyses were carried out,and the main components in the network interactions diagram between the extract of Physalis Calyx seu Fructus and the disease targets were screened,and among the active ingredients of extract of Physalis Calyx seu Fructus those ranked in the top 10 were selected as the core components.PPI analysis revealed that tumour necrosis factor (TNF),protein kinase,cysteine-aspartate protease (CASP3) and other proteins were the core targets of extract of Physalis Calyx seu Fructus against IB.GO function enrichment analysis revealed that it mainly involved hormone response,cell activation,membrane rafts,membrane microregions,protein kinase activity,phosphotransferase activity,etc.KEGG pathway enrichment analysis revealed that the pathway of extract of Physalis Calyx seu Fructus against IB was mainly related to PI3K-Akt signaling pathway.Molecular docking revealed that the 10 core components in the active ingredients of extract of Physalis Calyx seu Fructus had strong binding energies with 9 core targets.It was found that the docking energies of TNF to cyclohexanol,prostaglandin endoperoxide synthase 2 (PTGS2) to luteolin,and matrix metalloproteinase 9 (MMP9) to luteolin were smaller,with values of －10.5,－9.4 and －10.6 kJ/mol,respectively，determined by Auto Dock Vina.【Conclusion】 Based on UPLC-Q-TOF-MS technology,GNPS,network pharmacology and molecular docking technology,this study revealed that the extract of Physalis Calyx seu Fructus might regulate the occurrence and development of IB through the action of its active components luteolin and cycloartenol on the core targets of TNF and MMP9.The result of this study provided the theoretical basis for researching the potential molecular pharmacological mechanism of the extract of Physalis Calyx seu Fructus against IB.

Key words: extract of Physalis Calyx seu Fructus; avian infectious bronchitis; network pharmacology; UPLC-Q-TOF-MS