摘要
目的采用网络药理学方法和分子对接技术探讨经典名方泻白散治疗肺炎潜在作用机制。方法通过检索TCMSP、BATMAN-TCM数据库获取泻白散活性成分及作用靶点,通过DisGeNET、Gene Cards数据库获取肺炎的相关靶点,筛选得到泻白散治疗肺炎的活性成分及作用靶点,采用Cytoscape 3.6.0构建药物-成分-靶点-疾病作用网络。利用STRING数据库和Cytoscape 3.6.0软件构建泻白散治疗肺炎靶点间蛋白质-蛋白质互作关系(PPI)网络并筛选得到关键靶点及其PPI网络。利用DAVID数据库对关键靶点进行基因本体(gene ontology,GO)富集分析与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。最后利用AutoDock工具对泻白散成分和靶点进行分子对接。结果本研究通过构建药物-靶点-疾病网络,发现泻白散中74个活性成分可以作用于与肺炎相关的53个靶点,其中槲皮素、血根碱、山柰酚、β-谷甾醇等成分是潜在药效成分。利用拓扑学筛选得到关键靶点9个,包括白细胞介素8(IL8)、白细胞介素6(IL6)、白细胞介素1β(IL1B)、肿瘤坏死因子(TNF)等;GO分析获得90个条目,泻白散治疗肺炎可能涉及炎症反应、免疫应答、细胞因子活性等过程,KEGG分析获得41个条目,炎症性肠病、百日咳等通路可能是泻白散治疗肺炎的潜在通路,分子对接结果显示方中主要活性成分槲皮素、血根碱、山奈酚、β-谷甾醇等与核心靶点IL8,IL6,IL4和TNF等均能实现自发结合。结论中医经典名方泻白散中槲皮素、血根碱、山奈酚等活性成分可能通过炎症性肠病、百日咳等通路实现对肺炎的防治。
Objective To investigate the potential mechanism of the classical traditional Chinese medicine(TCM)formula Xie-Bai-San(XBS)in the treatment of pneumonia using a network pharmacology approach and molecular docking technology.Methods The active ingredients and action targets of XBS were obtained by searching in the TCMSP and BATMAN-TCM databases,and the relevant targets of pneumonia were gained from DisGeNET and Gene Cards databases.Then,the active ingredients and action targets of XBS against pneumonia were filtered out and the drug-component-target-disease network was developed.The STRING database and Cytoscape 3.6.0 software were used to construct the protein-protein interaction(PPI)network of targets of XBS against pneumonia and to screen the key targets and further get their PPI networks.The DAVID database was used to perform gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of key targets.Finally,the AutoDock tool was used to accomplish molecular docking of components and targets.Results In this study,74 active ingredients of Xie-Bai-San,among which quercetin,sanguinarine,kaempferol andβ-glutamine might be the potential components of XBS against pneumonia,were found to act on 53 targets of pneumonia by developing the drugcomponent-target-disease network.9 key targets were obtained by topological screening,including interleukin 8(IL8),interleukin 6(IL6),interleukin 1β(IL1 B),tumor necrosis factor(TNF),etc.90 GO terms were obtained by GO functional enrichment analysis,and inflammatory response,immune response,and cytokine activity could be involved in the treatment of pneumonia.41 signal pathways were obtained by KEGG pathway enrichment analysis,indicating that inflammatory bowel disease(IBD)and pertussis pathways might be the main pathways of XBS to treat pneumonia.The molecular docking results showed that main active ingredients such as quercetin,sanguinarine,kaempferol,β-glutamine in XBS could spontaneously bind to the key targets like IL8,IL6,IL4 and TNF.Conlusion Quercetin,sanguinarine,and kaempferol in XBS might prevent and treat pneumonia through pathways such as inflammatory bowel disease and pertussis.
作者
向泽栋
李震
张兵
张宏萌
王少平
张加余
于海涛
代龙
高鹏
无
Xiang Zedong;Li Zhen;Zhang Bing;Zhang Hongmeng;Wang Shaoping;Zhang Jiayu;Yu Haitao;Dai Long;Gao Peng;无(College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Shandong Food and Drug Evaluation and Inspection Center,Jinan 250014,China;School of Pharmacy,Binzhou Medical University,Yantai 264003,China;Shandong Yuze Institute of Pharmaceutical and Health Industry Technology Co.,Ltd.,Dezhou 251200,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2021年第6期1812-1820,共9页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家卫健委重大科技专项课题(2018ZX09721-004):基于经方一致性评价技术的经典名方研究与开发,负责人:刘菊妍。
关键词
泻白散
经典名方
网络药理学
肺炎
Xie-Bai-San
Classical formula
Network pharmacology
Pneumonia
作者简介
通讯作者:高鹏,教授,硕士生导师,主要研究方向:中药制剂研究与新药研发。
