基于网络药理学和分子对接技术探讨国医大师张震疏调气机的用药机制

Discussion on the medication mechanism of TCM master ZHANG Zhen’s thought of regulating Qi activity based on network pharmacology and molecular docking technology

目的:运用网络药理学及分子对接技术探讨张震教授运用疏调气机汤治疗抑郁症的潜在作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)收集药物活性成分及靶标,利用Cytoscape 3.8.0构建“药物-活性成分-靶点”网络图;在OMIN、Genecards、Drugbank等多个数据库中以“depression”为关键词检索疾病相关靶点,利用STRING数据库获取蛋白质-蛋白质相互作用网络图并进行拓扑分析。运行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。将关键成分与核心靶点进行分子对接验证并绘制相应对接构象。结果:疏调气机汤共含233个活性成分,潜在作用靶点有258个,筛选出丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、环腺苷酸反应元件结合蛋白1(cAMP Responsive Element Binding Protein 1,CREB1)、热休克蛋白90α家族A类成员1(Heat Shock Protein 90 Alpha Family Class A Member 1,HSP90AA1)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)1等共18个核心靶标。GO富集结果共3 075条;KEGG富集结果涉及193条信号通路。分子对接结果显示,β-谷甾醇与AKT1、槲皮素与AKT1、木犀草素与HSP90AA1、异鼠李素与FOS原癌基因(Fos Proto-Oncogene,FOS)结合性能最佳。结论:疏调气机汤通过“多成分、多通路、多靶点”积极拮抗抑郁,为挖掘抗抑郁复方及化合物奠定了基础和依据。

bjective:To investigate the potential mechanism of the Shutiao Qiji decoction(疏调气机汤)of Professor ZHANG Zhen in the treatment of depression by network pharmacology and molecular docking techniques.Methods:The active components and targets of drugs were collected by TCMSP,and the drug-active component-target network diagram was constructed by Cytoscape 3.8.0.The disease-related targets were searched with depression as the key word in multiple databases such as OMIN,Genecards,Drugbank,etc.The PPI network diagram was obtained and topological analysis was performed using the String database.GO and KEGG enrichment analyses were performed to verify the molecular docking of the key components with the core targets and plot the corresponding docking conformation.Results:The Shutiao Qiji decoction contained 233 active components,258 potential targets,and 18 core targets such as AKT1,CREB1,HSP90AA1 and MAPK1.A total of 3075 GO enrichment results.KEGG results involved 193 signaling pathways.The results of molecular docking showed thatβ-sitosterol and AKT1,quercetin and AKT1,luteolin and HSP90AA1,isorhamnetin and FOS had the best binding properties.Conclusion:The Shutiao Qiji decoction can actively antagonize depression through multi-component,multi-channel and multi-target,which lays a foundation and basis for mining antidepressant compounds and compounds.