基于网络药理学和分子对接探讨双夏汤治疗不寐的相关作用研究

Study on the effect of the Shuangxia decoction on insomnia based on network pharmacology and molecular docking

目的:通过网络药理学和分子对接技术探讨双夏汤治疗不寐的主要活性成分及作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库获取双夏汤活性成分,通过Swiss Target Prediction数据库预测其成分的作用靶点,结合OMIM、Gencards、Drugbank数据库获取不寐的作用靶点,取二者共同作用的靶点制作韦恩图。运用Cytoscape 3.7.2软件筛选并构建“活性成分-核心靶点”网络,利用STRING数据库构建蛋白质-蛋白质相互作用网络图,筛选出核心靶点后对其进行基因本体论(GO)富集分析和京都基因与基因组学百科全书(KEGG)通路分析,最后将核心靶点与主要活性成分进行分子对接验证。结果:筛选得到双夏汤治疗不寐的22个活性成分和115个药物与疾病的共同靶点,推测丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、白细胞介素(Interleukin,IL)-6、淀粉样蛋白前体(Beta Amyloid A4 Protein,APP)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等关键靶点主要作用于G蛋白偶联受体信号通路、神经递质水平的调节、神经活性配体-受体相互作用等信号通路。分子对接结果表明,主要活性成分能够分别与核心靶点对接良好。结论:双夏汤可能通过保护中枢神经细胞,下调炎性因子表达,影响神经递质的释放和传递来发挥治疗不寐的作用。

Objective:To explore the main active components and mechanism of the Shuangxia decoction(双夏汤)in the treatment of insomnia by network pharmacology method and molecular docking.Methods:Firstly,TCMSP database was used to obtain the active ingredients of the two drugs in the Shuangxia decoction,and the target prediction of the active ingredients was carried out by Swiss Target Prediction database.Next,the targets of insomnia were obtained by combining OMIM,GenCards and Drugbank database,and then the potential targets of drug targets and disease targets acting together were selected to make the Venn diagram.Then,Cytoscape 3.7.2 software was used to screen and construct the“active component-core target”network,and the STRING database was used to construct the protein-protein interaction network,and the core targets were screened according to the magnitude of mutual relationship.Then,the GO enrichment analysis and KEGG pathway analysis of the core target were performed using R language.Finally,the core genes were verified by molecular docking with the main active ingredients.Results:In this study,a total of 22 active components of the Shuangxia decoction and 115 common targets of drugs and diseases were screened.AKT1,IL-6,APP,TNF and other key targets mainly act on G protein coupled receptor signaling pathway,regulation of neurotransmitter level,and neuroactive ligand receptor interaction.The molecular docking results showed that the main active compounds could bind to the core target and showed good affinity.Conclusion:The Shuangxia decoction may play a role in the treatment of insomnia by protecting central nerve cells,down-regulating the expression of inflammatory factors,and affecting the release and transmission of neurotransmitters.