世界中医药
文章摘要
引用本文:刘少姣1,刘雪梅2,傅晨2,梁晓3,曾子修1,徐榛敏1,杜琬晴1,吴艺帆1,罗超琴1,张允岭3.基于网络药理学的复方苁蓉益智胶囊治疗血管性痴呆的分子机制研究[J].世界中医药,2023,(08):.  
基于网络药理学的复方苁蓉益智胶囊治疗血管性痴呆的分子机制研究
Research on Molecular Mechanism of Compound Congrong Yizhi Capsule in Treating Vascular Dementia Based on Network Pharmacology
投稿时间:2021-05-27  
DOI:10.3969/j.issn.1673-7202.2023.08.001
中文关键词:  复方苁蓉益智胶囊  血管性痴呆  网络药理学  分子对接  作用机制  信号通路  靶点  富集分析
English Keywords:Compound Congrong Yizhi Capsule  Vascular dementia  Network pharmacology  Molecular docking  Mechanism  Signal pathway  Target  Enrichment analysis
基金项目:中央级公益性科研院所基本科研业务费专项资金资助项目(ZZ13-024-3);国家中医药管理局中医药传承与创新“百千万”人才工程(岐黄学者)——国家中医药领军人才支持计划项目(国中医药人教发[2018]12号)
作者单位
刘少姣1,刘雪梅2,傅晨2,梁晓3,曾子修1,徐榛敏1,杜琬晴1,吴艺帆1,罗超琴1,张允岭3 1 北京中医药大学研究生院北京100029 2 北京中医药大学东方医院北京100078 3 中国中医科学院西苑医院北京100091 
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中文摘要:
      目的:对复方苁蓉益智胶囊(Compound Desert Cistanche Intelligence-improving Capsule)治疗血管性痴呆(VaD)的药理作用机制进行探讨。方法:基于网络药理学和分子对接的方法,通过中药系统药理学数据库与分析平台(TCMSP)获取复方苁蓉益智胶囊中各药物的活性成分,并通过SwissTarget Prediction数据库预测药物活性成分的作用靶点;通过GeneCards、在线人类孟德尔遗传数据库(OMIM)、DrugBank数据库获取血管性痴呆的疾病靶点。通过STRING 11.0数据库和Cytoscape 3.8.2构建蛋白质相互作用(PPI)网络并挖掘网络中潜在的蛋白质功能模块及核心网络;通过DAVID数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析,采用Cytoscape 3.8.2构建“药物-活性成分-靶点-通路”网络图,采用分子对接技术对PPI网络及“药物-活性成分-靶点-通路”网络图结果进行验证。结果:筛选出35个主要活性成分,涉及134个靶点,其中主要活性成分包括亚美罂粟碱(Armepavine)、甘草素(DFV)、异鼠李素(Isorhamnetin)等;关键靶点包括淀粉样前体蛋白(APP)、磷脂酰肌醇-3-激酶催化亚单位α(PIK3CA)、酪氨酸蛋白激酶SRC(SRC)、磷脂酰肌醇3-激酶调控亚基1(PIK3R1)、促分裂原活化的蛋白激酶1(MAPK1)、肿瘤蛋白53(TP53)、促分裂原活化的蛋白激酶3(MAPK3)、原癌基因c-Jun(JUN)、丝氨酸/苏氨酸蛋白激酶(AKT1)、血管内皮生长因子A(VEGFA)、表皮生长因子受体(EGFR)、凝血酶F2(F2)等;复方苁蓉益智胶囊治疗血管性痴呆的生物学通路主要作用在癌症信号通路、Rap1信号通路、PI3K-AKT信号通路、黏着斑、Ras信号通路、神经活性配体-受体相互作用等。分子对接结果验证提示主要活性成分与靶点之间具有较好的结合能力。结论:本研究初步揭示了复方苁蓉益智胶囊治疗血管性痴呆的机制可能是通过多组分、多靶点、多途径协同发挥作用,为接下来的深入研究提供参考。
English Summary:
      To explore the pharmacological mechanism of the compound Congrong Yizhi Capsule in treating vascular dementia.Methods:Based on the method of network pharmacology and molecular docking,the active ingredients of each drug in the compound Congrong Yizhi Capsule are obtained through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and the targets of the active ingredients of the drug are predicted through the SwissTarget prediction database.The disease targets of vascular dementia are obtained through GeneCards,online Mendelian inheritance in man(OMIM),and DRUGBANK databases.A protein-protein interaction(PPI) network is constructed with STRING 11.0 database and Cytoscape 3.8.0 to explore potential protein functional modules and core networks in the network; DAVID database is used to perform gene ontology(GO) enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis,and Cytoscape 3.8.0 is adopted to construct the “drug-active ingredient-target-pathway” network diagram.In addition,molecular docking technology is employed to verify the results of the PPI network and the “drug-active ingredient-target-pathway” network diagram.Results:Thirty-five main active ingredients are screened,involving 134 targets.Among them,the main active ingredients include Armepavine,DFV,Isorhamnetin,etc.; key targets include amyloid precusor protein(APP),PIK3CA,SRC,PIK3R1,MAPK1,TP53,MAPK3,JUN,AKT1,vascular endothelial growth factor A(VEGFA),EGFR,F2,etc.; the biological pathways of compound Congrong Yizhi Capsule in treating vascular dementia act mainly in cancer signal pathway,Rap1 signal pathway,PI3K-AKT signal pathway,focal adhesion,Ras signal pathway,neuroactive ligand-receptor interaction,etc.The verification of the molecular docking results indicates that the main active ingredient has an excellent binding ability with the target.Conclusion:This study preliminarily reveals that the compound Congrong Yizhi Capsule may treat vascular dementia through multi-component,multi-target,and multi-channel cooperation,which provides a reference for the subsequent in-depth research.
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