基于网络药理学和分子对接技术探究夜交藤治疗失眠的作用机制

Discussion on the mechanism of Polygoni multiflori Caulis in treating insomnia based on network pharmacological prediction and molecular docking technology

目的:采用网络药理学方法及分子对接技术探究夜交藤治疗失眠的分子作用机制。方法:基于文献研究并结合公共数据库筛选得到夜交藤主要有效成分,对其进行靶标预测。收集失眠相关基因,构建“药物-成分-疾病-靶点”网络并进行分析。利用蛋白互作网络建立夜交藤的相互作用靶标。通过R语言和Bioconductor数据库对潜在靶点进行基因本体(Gene Ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。最后对得到的有效成分与核心靶点应用AutoDock Vina和Pymol进行分子对接。结果:筛选得到夜交藤中15个有效成分,对应靶点115个,核心靶点39个,如丝氨酸/苏氨酸蛋白激酶1(AKT Serine/Threonine Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、雌激素受体1(Estrogen Receptor 1,ESR1)、淀粉样β前体蛋白(Amyloid beta Precurs Protein,APP)等核心靶标。此外,还涉及TNF信号通路、哺乳动物雷帕霉素靶蛋白信号通路、雌激素信号通路等。分子对接结果显示有效成分与核心靶点具有较好的结合能。结论:本研究初步探讨了夜交藤治疗失眠的作用机制,有利于指导临床用药。

Objective:This study was aimed to identify the bioactive components and potential mechanisms of Polygoni multiflori Caulis for insomnia treatment by integrated network pharmacology approaches and molecular docking technology.Methods:First,based on literature research and combined with online databases,the main active components of Polygoni multiflori Caulis were screened and the target prediction of them was made.After that,collecting the targets interacting with insomnia as well as establishing a“drug-componentdisease-target”interaction network.Then,Using protein-protein interaction network,the interaction targets of Polygoni multiflori Caulis on insomnia were constructed.Gene ontology functional and Kyoto encyclopedia of genes and genomes pathways enrichment analysis were carried out using R language and Bioconductor database.Finally,AutoDock Vina and Pymol were used to conduct molecular docking between the active components and key targets.Results:After screening,we got 15 active ingredients,115 related potential targets,and 39 key targets,such as AKT1,TNF,ESR1,APP and other key targets.In addition,TNF signaling pathway,mTOR signaling pathway and Estrogen signaling pathway are also involved.The results of molecular docking show that the active components have good binding energy with these key targets.Conclusion:Network pharmacology and molecular docking method can reveal the potential mechanism of Polygoni multiflori Caulis in the treatment of insomnia,which is helpful to guide clinical medication.