摘要
目的探讨丹参-当归治疗缺血性脑卒中(CIS)的潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、Swiss TargetPrediction数据库获取丹参和当归的活性成分及作用靶点,并通过检索PubMed、中国知网相关文献进行补充;通过GeneCards、人类孟德尔遗传数据库(OMIM)、DisGeNET数据库获取CIS的潜在靶点;将丹参-当归治疗CIS的共有靶点导入String 11.0平台,构建活性成分与疾病靶点蛋白的蛋白相互作用(PPI)网络,利用Cytoscape 3.8.2软件构建疾病-药物-活性成分-靶点可视化网络;将共有靶点导入DAVID数据库进行基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,并利用Cytoscape 3.8.2软件构建活性成分-核心靶点-通路网络;利用AutoDock软件对疾病-药物-活性成分-靶点网络中度值排名前6的核心靶点和活性成分进行分子对接验证。结果共检索到82种活性成分,其中丹参65个、当归17个,潜在作用靶点787个,疾病靶点671个,共有靶点76个。度值排名前6的活性成分为丹参醇B、丹参新醌D、木犀草素、阿魏酸、藁本内酯、丹参酮ⅡA,核心靶点为MAPK14,MAPK1,AKT1,PTGS2,EGFR,JAK2。共获得GO功能条目2545个,其中生物学过程2244个,细胞组成128个,分子功能173个,分别涉及对脂多糖的反应、膜筏、内肽酶活性等;KEGG信号通路152条,主要涉及PI3K-Akt信号通路、脂质和动脉粥样硬化、钙信号通路等。分子对接结果证明了6种活性成分与其相应核心靶点均有较好的结合活性。结论丹参-当归治疗CIS具有多成分-多靶点-多通路的调控特点,其作用机制可能与抗炎、抗氧化应激、抗神经细胞凋亡、调节自噬功能等有关。
Objective To investigate the potential mechanism of Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix in the treatment of cerebral ischemic stroke(CIS).Methods The active ingredients and targets of Salviae Miltiorrhizae Radix et Rhizoma and Angelicae Sinensis Radix were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Swiss TargetPrediction database,and relevant literature in the PubMed and CNKI were searched for supplementary analysis.The potential targets of CIS were obtained by the GeneCards,Online Mendelian Inheritance in Man(OMIM)and DisGeNET databases.The common targets of active ingredients in Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix and CIS were imported into the String 11.0 platform to construct a protein-protein interaction(PPI)network,and a disease-drug-active ingredient-target visualization network was constructed by the Cytoscape 3.8.2 software.The common targets were imported into the DAVID database for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and an active ingredient-core target-pathway network was constructed by the Cytoscape 3.8.2 software.The top six core targets and active ingredients with high degree in the disease-drug-active ingredient-target network were selected for molecular docking verification by the AutoDock software.Results A total of 82 active ingredients(65 from Salviae Miltiorrhizae Radix et Rhizoma,17 from Angelicae Sinensis Radix),787 potential targets,671 disease targets and 76 common targets were obtained.The top six active ingredients with high degree were tanshinol B,danshenxinkun D,luteolin,ferulic acid,ligustilide and tanshinoneⅡA,the top six core targets were MAPK14,MAPK1,AKT1,PTGS2,EGFR and JAK2.A total of 2545 GO functional entries were obtained,including 2244 biological processes,128 cellular compositions and 173 molecular functions,involving response to lipopolysaccharide,membrane raft,endopeptidase activity and so on respectively.A total of 152 KEGG signaling pathways were obtained,mainly involving PI3K-Akt signaling pathway,lipid and atherosclerosis,calcium signaling pathway and so on.The molecular docking showed that six active ingredients had good binding energies with their corresponding core targets.Conclusion Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix in the treatment of CIS has the characteristics of multiple-ingredients,multiple-targets and multiple-pathways regulation.Its mechanism may be related to the anti-inflammatory,antioxidant stress,anti-neuronal apoptosis and autophagy function regulation.
作者
王红
蒋征
刘玲
付媛媛
崔永伟
瞿城
WANG Hong;JIANG Zheng;LIU Ling;FU Yuanyuan;CUI Yongwei;QU Cheng(Department of Pharmacy,The South Part of Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine·Lishui District Hospital of Traditional Chinese Medicine,Nanjing,Jiangsu,China 211200;Department of Pharmacy,The Affiliated Hospital of Yangzhou University Medical College,Nanjing,Jiangsu,China 211200;College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,Jiangsu,China 210046)
出处
《中国药业》
CAS
2024年第6期40-48,共9页
China Pharmaceuticals
基金
国家自然科学基金[82204597]
南京市中医药青年人才培养计划项目[ZYQ20059]
南京药学会-常州四药医院药学科研基金[2019YX023]
南京市中医药科技专项中医药青年人才项目[ZYQN202209]。
关键词
丹参
当归
药对
缺血性脑卒中
作用机制
网络药理学
分子对接技术
Salviae Miltiorrhizae Radix et Rhizoma
Angelicae Sinensis Radix
drug pair
cerebral ischemic stroke
mechanism
network pharmacology
molecular docking technology
