基于网络药理及分子对接技术拓扑分析人参-川芎治疗血管性痴呆的作用机制

Topological analysis of treating vascular dementia with Reushen-Chuanxiong based on network pharmacology and molecular docking technology

目的:基于网络药理学及分子对接技术拓扑分析人参-川芎药对治疗血管性痴呆的分子作用机制,为临床应用人参-川芎药对提供依据。方法:首先通过检索中药系统药理学数据库分析平台(TCMSP)数据库与相关文献查找,获得人参-川芎药对的有效活性成分及作用靶点;通过GeneCards等数据库获取血管性痴呆的疾病靶点;利用微生信在线平台将人参-川芎药对与血管性痴呆的靶点制作韦恩图取交集;借助STRING数据库构建蛋白质-蛋白质相互作用网络模型,并运用CytoScape 3.9.0软件进行拓扑分析;使用CytoScape3.9.0软件构建人参-川芎药对与血管性痴呆的“成分-靶点”网络图;应用DAVID数据库进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析;最后应用AutoDock Vina等分子对接软件验证预测结果。结果:筛选出人参-川芎活性成分26个,经拓扑分析筛选出SRC原癌基因(SRC Proto-Oncogene,SRC)、磷脂酰肌醇-3-激酶调节亚基1(Phosphoinositide-3-Kinase Regulatory Subunit 1,PIK3R1)、磷脂酰肌醇-3-激酶催化亚基α(Phosphatidylinositol-3-Kinase Catalytic Subunit Alpha,PIK3CA)、磷脂酰肌醇-3-激酶催化亚基β(Phosphatidylinositol-3-Kinase Catalytic Subunit Beta,PIK3CB)、磷脂酰肌醇-3-激酶催化亚基δ(Phosphatidylinositol-3-Kinase Catalytic Subunit Delta,PIK3CD)等20个核心靶点。KEGG分析显示靶点主要富集在神经活性配体-受体相互作用、钙离子信号通路、环磷酸腺苷(Cyclic Adenosine Monophosphate,cAMP)信号通路、癌症的途径等信号通路。最后通过分子对接技术,验证核心靶点与对应活性成分间具有良好的结合活性。结论:人参-川芎药对化合物通过多种成分、多个靶点、多条通路实现对血管性痴呆的治疗作用,为后续药对治疗血管性痴呆的运用提供研究基础。

Objective:To analyze the molecular mechanism of Renshen(Radix Ginseng)-Chuangxiong(Rhizoma Chuanxiong)in the treatment of vascular dementia(VD)based on network pharmacology and molecular docking technology topology,and to provide a basis for clinical application of Renshen-Chuanxiong.Methods:Firstly,the effective active components and targets of Renshen�Chuanxiong were obtained by searching TCMSP database and related literature.The disease targets of VD were obtained through databases such as GeneCards.Using Weishengxin online platform,the intersection of Renshen-Chuanxiong and VD target was made by Wayne diagram.The protein interaction network model was constructed by STRING database,and the topology analysis was carried out by CytoScape 3.9.0 software.CytoScape 3.9.0 software was used to construct the component-target network diagram of Renshen-Chuanxiong and VD.DAVID database was used for GO analysis and KEGG pathway enrichment analysis.Finally,AutoDock Vina and other molecular docking software were used to verify the prediction results.Results:A total of 26 active components of Renshen-Chuanxiong were screened out,and 20 core targets such as SRC,PIK3R1,PIK3CA,PIK3CB and PIK3CD were screened out by topology analysis.KEGG analysis showed that the targets were mainly enriched in neuroactive ligand-receptor interaction,calcium signaling pathway,cAMP signaling pathway,cancer pathway and other signaling pathways.Finally,molecular docking technology was used to verify that the core target had good binding activity with the corresponding active components.Conclusion:Renshen-Chuanxiong compounds achieve the therapeutic effect on VD through multiple components,multiple targets,and multiple pathways,providing a research basis for the use of subsequent drug pairs in the treatment of VD.