克咳胶囊抗急性呼吸道传染病及并发咳嗽症的网络分子机制研究  

Study on the Network Molecular Mechanism of Keke Capsules against Acute Respiratory Infection and Cough Complications

作　　者：蒲健 于宁 耿丽波 肖淦辰 Pu Jian;Yu Ning;Geng Libo;Xiao Ganchen(Guizhou Yibai Pharmaceutical Co.LTD.,Guiyang 550008,China;First Affilia-ted Hospital of Guizhou University of Chinese Medicine)

机构地区：[1]贵州益佰制药股份有限公司,贵阳550008 [2]贵州中医药大学第一附属医院

出　　处：《中国药师》2022年第5期782-788,共7页China Pharmacist

基　　金：国家自然科学基金项目(编号:82074284);贵州省科技计划项目(编号:黔科合支持[2020]4Z004号)。

摘　　要：目的:探究克咳胶囊对于急性呼吸道传染病及并发症咳嗽的保护、治疗机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)、有机小分子生物活性数据库(PubChem)获取克咳胶囊的有效成分,并以口服吸收利用度、类药性对活性成分做初步筛选并获取结构成分;通过瑞士靶点预测(Swiss Target Prediction)预测潜在活性成分的靶点信息;通过基因名片数据库(GeneCards)检索汇总急性呼吸道传染病相关靶点;成分靶点和疾病靶点通过映射后导入邻近基因重复实例搜索工具(STRING)平台和生物信息学资源数据库(DAVID)平台构建蛋白互作网络(PPI)和富集分析,分析结果经生物信息分析软件Cytoscape和R进行可视化;最后将核心靶点与成分进行分子对接以初步验证靶点的可靠性。结果:筛选后共获得克咳胶囊潜在有效成分151个,急性呼吸道传染病靶点334个,咳嗽靶点1238个,映射后获得克咳胶囊抗急性呼吸道感染病24个靶点和镇咳作用10个靶点。基因本体(GO)分析结果表明,克咳胶囊可通过病毒进入宿主细胞、调控细胞增殖、病毒受体活动等过程调节机体,京都基因与基因组百科全书(KEGG)通路富集分析结果显示克咳胶囊的体内调节可能与肾素⁃血管紧张素系统(RAS)、肾素分泌、RAS信号通路等相关。PPI分析发现血管内皮生长因子A(VEGFA)、血管紧张素转化酶(ACE)、表皮生长因子受体(EGFR)为核心靶点,通过分子对接发现大部分潜在有效成分能与核心靶点结合且结合能<-5 kcal·mol^(-1)。结论:克咳胶囊可通过多途径多靶点对急性呼吸道感染病及咳嗽症状起到一定的治疗作用。Objective:To investigate the protective and therapeutic mechanism of Keke capsules against acute respiratory infection(ARI)and cough complications.Methods:The active ingredients of Keke capsules were obtained from TCMSP and PubChem databases,and the active ingredients were preliminarily screened by oral absorption and utilization and drug-like properties,and structural components were obtained.The drug targets and disease targets were mapped and then imported into STRING and DAVID platforms for PPI and enrichment analysis,and the results were visualized by Cytoscape and R.Finally,the core targets were molecular docked with the components to verify the reliability of the targets.Results:After screening,a total of 151 potential active ingredients,334 ARI targets and 1238 cough targets were obtained,24 anti-ARI targets and 10 cough suppressant targets were mapped,and the results of GO analysis showed that Keke capsules could regulate the body through the processes of virus entry into host cells,regulation of cell proliferation and viral receptor activity.PPI analysis revealed that VEGFA,ACE and EGFR were the core targets,and most of the potential active ingredients could bind to the core targets through molecular docking and the binding energy was<-5 kcal·mol^(-1).Conclusion:Keke capsules may play a therapeutic role in the treatment of ARI and cough symptoms through multiple pathways and targets.

关 键 词：克咳胶囊 急性呼吸道感染病 咳嗽 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]