摘要
目的运用网络药理学探究桑白皮汤治疗慢性阻塞性肺病急性加重期的关键靶点和分子机制。方法利用中药系统药理学数据库与分析平台(TCMSP)数据库检索桑白皮汤的活性成分,预测其对应靶点;利用基因库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、药品数据与综合药物靶点信息DrugBank数据库检索慢性阻塞性肺病急性加重疾病相关靶点,利用全球蛋白质资源(Uniprot)数据库将预测靶点和疾病靶点名称标准化后筛选出交集靶点,利用Cytoscape3.6.0绘制并分析中药-成分-靶点网络图。将共同靶点导入检索互作用基因/蛋白质的搜索工具(STRING)数据库获得蛋白质相互作用网络并利用Cytoscape3.6.0 CytoNCA插件筛选出核心靶点。将共同靶点导入富集分析库(Metascape)数据库进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析,并利用自动对接工具(Auto Dock Tools)软件进行分子对接。结果桑白皮汤有效活性成分126个,预测对应靶点1351个,疾病相关靶点2296个,主要活性成分为槲皮素、木犀草素、山柰酚、汉黄芩素、β谷甾醇,核心靶点为肿瘤坏死因子(TNF)、白细胞介素6(IL-6)、肿瘤蛋白p53(TP53)、丝裂原激活蛋白激酶8(MAPK8)、MAPK14。GO富集分析共获得2720条,KEGG富集分析获得信号通路334条,分子对接结果表明主要活性成分可以和核心靶点结合,结合构象稳定。结论桑白皮汤可能通过多种有效成分、多个作用靶点和信号通路发挥抗炎、抗氧化等生物作用,进而具有治疗慢性阻塞性肺病急性加重的作用。
Objective To identify the key targets and molecular mechanisms of Sangbaipi decoction in the treatment of acute exacerbations of chronic obstructive pulmonary disease(AECOPD)by using network pharmacology.Methods The active components of Sangbaipi Decoction were searched in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database,with the corresponding targets predicted.The related targets of AECOPD were searched within gene banks,OMIM and Drugbank.The names of prediction targets and disease targets were standardized by UniProt,and the intersection targets were selected.TCM component target network diagram was drawn and analyzed by Cytoscape 3.6.0.The common targets were imported into the metascape database for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and molecular docking was carried out by using auto dock tools software.Results A total of 126 active ingredients in Sangbaipi decoction,1351 predicted corresponding targets and 2296 disease-related targets were detected.The main active ingredients include quercetin,luteolin,kaempferol,wogoninβ.The core targets of sitosterol involve tumor necrosis factor(TNF),interleukin-6(IL-6),tumor protein p53(TP53),mitogen activated protein kinase 8(MAPK8)and MAPK14.A total of 2720 signals were obtained from GO enrichment analysis and 334 signal pathways were obtained from KEGG enrichment analysis.The molecular docking results showed that the main active components can bind to the core target,at a stable the binding conformation.Conclusion Sangbaipi decoction may have anti-inflammatory,anti-oxidant and other biological effects through multiple active ingredients,multiple targets and signalpathways,thus effectively treatingAECOPD.
作者
王坤
朱慧志
杨磊
徐晴雯
任冯春
刘向国
万磊
WANG Kun;ZHU Huizhi;YANG Lei;XU Qingwen;REN Fengchun;LIU Xiangguo;WAN Lei(Key Laboratory of Xin'an Medical Ministry of Education,Anhui University of Traditional Chinese Medicine,Hefei 230031,China;Department of Internal Medicine of the First Affiliated Hospital,Anhui University of Traditional Chinese Medicine,Hefei 230031,China;Molecular Laboratory of College of Integrated Traditional Chinese and Western Medicine,Anhui University of Traditional Chinese Medicine,Hefei 230031,China)
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2023年第2期130-137,共8页
Chinese Journal of Cellular and Molecular Immunology
基金
国家自然科学基金(81973655)。
关键词
桑白皮汤
慢性阻塞性肺病急性加重
网络药理学
关键靶点
分子机制
分子对接
Sangbaipi decoction
acute exacerbation of chronic obstructive pulmonary disease
network pharmacology
key targets
molecularmechanism
moleculardocking
