基于网络药理学和分子对接技术探究脑络欣通治疗缺血性脑卒中的机制

Mechanism of Naoluoxintong in Treatment of Ischemic Stroke:An Analysis Based on Network Pharmacology and Molecular Docking

目的采用网络药理学方法探究益气活血方脑络欣通治疗缺血性脑卒中(ischemic stroke,IS)的作用机制,并通过分子对接技术进行初步验证。方法通过TCMSP、ETCM、化学专业数据库及文献筛选脑络欣通活性成分及作用靶点,通过OMIM、DisGeNET、GeneCards以及Drugbank数据库挖掘IS相关靶点;将交集靶点导入STRING平台和Cytoscape 3.8.2软件构建PPI网络并通过拓扑分析获得核心靶点,同时构建“中药—活性成分—核心靶点—疾病”可视化网络图;运用R软件进行GO功能及KEGG通路富集分析。最后借助Auto Dock Tools软件以及PyMOL软件进行分子对接和可视化。结果脑络欣通的潜在活性成分78个,治疗IS的潜在作用靶点200个,核心靶点包括STAT3、JUN、MAPK1、TP53等;作用较突出的活性成分包括槲皮素、β-谷甾醇、山柰酚、木犀草素等。进一步的生物功能分析获得150条信号通路,包括PI3K-AKT信号通路、HIF-1信号通路、FoxO信号通路等关键通路。分子对接结果表明关键活性成分与核心靶点之间存在分子结合位点,并有较强的结合活性。结论益气活血方脑络欣通可能是通过多成分、多靶点协同作用于氧化应激、炎症反应、细胞凋亡、自噬等生理病理环节,从而发挥治疗IS的作用。

Objective To investigate the mechanism of the Qi-tonifying and blood-activating prescription Naoluoxintong in the treatment of ischemic stroke(IS)based on network pharmacology and molecular docking for preliminary verification.Methods TCMSP,ETCM,chemical databases,and related literature were used to screen for the active components of Naoluoxintong and their action targets,and OMIM,DisGeNET,GeneCards,and Drugbank databases were used to obtain the targets related to IS.The intersecting targets were then imported into STRING platform and Cytoscape 3.8.2 software to construct a protein-protein interaction network,and a topology analysis was performed to obtain the core targets.A traditional Chinese medicine-active component-core target-disease visualized network was also constructed.R software was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis,and AutoDockTools and PyMOL were used to perform molecular docking and visualization.Results There were 78 potential active components in Naoluoxintong and 200 potential action targets for the treatment of IS;the core targets included STAT3,JUN,MAPK1,and TP53,and the active components with a marked effect included quercetin,β-sitosterol,kaempferol,and luteolin.The biological function analysis obtained 150 signaling pathways,including the key pathways such as the PI3K-AKT signaling pathway,the HIF-1 signaling pathway,and the FoxO signaling pathway.Molecular docking showed molecular binding sites between the key active components and the core targets,with a relatively strong binding activity.Conclusion The Qi-tonifying and blood-activating prescription Naoluoxintong exerts a therapeutic effect on IS by acting on the pathological links such as oxidative stress,inflammatory response,cell apoptosis,and autophagy through a synergistic role between multiple components and targets.