基于网络药理学和分子对接探索脑栓通胶囊治疗脑梗死的潜在机制研究

Study on the potential mechanism of naoshuantong capsule in treating cerebral infarction based on network pharmacology and molecular docking

目的采用网络药理学和分子对接技术探讨脑栓通胶囊治疗脑梗死的可能作用机制。方法基于TCMSP数据库筛选得到脑栓通胶囊的主要有效成分和靶标。同时通过GeneCards、OMIM、PharmGKB、TTD和DrugBank数据库收集脑梗死相关靶标,并利用InteractiVenn平台取药物与疾病的交集靶标。利用Cytoscape软件构建“活性成分-疾病靶点”网络模型。运用STRING数据库和Cytoscape软件构建蛋白相互作用网络图,根据相互关系大小筛选核心靶标。运用R语言对交集靶点进行GO功能分析和KEGG通路富集分析。最后运用AutoDock Vina和Pymol将“活性成分-疾病靶点”网络中的活性成分与蛋白靶点进行分子对接。结果收集脑栓通胶囊活性成分23种,相关潜在靶点264个;脑梗死相关靶点2043个;取两者交集得到共同靶点149种。主要作用于JUN、TNF、IL6和NFKBIA等多个靶标,靶点主要涉及TNF信号通路、IL-17信号通路、NF-κB信号通路和细胞死亡等通路以发挥治疗脑梗死作用。分子对接结果显示,网络中药物的活性成分与靶点蛋白结合较好。结论本研究通过网络药理学、分子对接以及生物信息学分析初步揭示了脑栓通胶囊多成分、多靶点、多通路治疗脑梗死的潜在机制。

Objective To explore the possible mechanism of Naoshuantong capsule in the treatment of cerebral infarction by network pharmacology and molecular docking technology.Methods The main active ingredients and targets of Naoshuantong Capsule were screened based on the TCMSP database.At the same time,the targets related to cerebral infarction were collected through GeneCards,OMIM,PharmGKB,TTD and DrugBank databases,and the intersection targets of drugs and diseases were obtained using InteractiVenn platform.Cytoscape software was used to construct the“active ingredient-disease target”network model.STRING database and Cytoscape software were used to construct protein interaction network diagrams,and core targets were screened according to the degree.GO functional analysis and KEGG pathway enrichment analysis were performed on intersecting targets using R language.Finally,AutoDock Vina and Symol were used to molecularly dock the active components in the“active ingredient-disease target”network with protein targets.Results 23 active ingredients and 264 related potential targets of Naoshuantong Capsule were collected;2,043 targets related to cerebral infarction were also collected;149 common targets were obtained by the intersection of the two.It mainly acts on JUN,TNF,IL6,NFKBIA and so on,which mainly involve TNF signaling pathway,IL-17 signaling pathway,NF-kappa B signaling pathway and apoptosis pathway to play a role in the treatment of cerebral infarction.Molecular docking results showed that the active components of drugs in the network bind well to target proteins.Conclusion This study preliminarily revealed the potential multi-component,multi-target and multi-pathway mechanism of Naoshuantong Capsule for cerebral infarction by network pharmacology,molecular docking and bioinformatics analysis.