基于网络药理学及分子对接技术探讨药对“茯苓-半夏”干预抑郁症的机制研究

Study on the mechanism of intervention of "tuckahoe-pinellia ternata" on depression based on network pharmacology and molecular docking technology

目的 运用网络药理学和分子对接的方法研究“茯苓-半夏”干预抑郁症的作用机制,旨在为基础研究及临床应用提供依据。方法 通过TCMSP、pubchem和pharmmapper数据库检索并筛选药对“茯苓-半夏”的活性成分以及作用靶点,利用DrugBank、GeneCards、OMIM数据库筛选抑郁症相关的疾病靶点,取两者的交集靶点;利用STRING11.5数据库获得蛋白互作关系,并通过Cytoscape3.8.2软件构建PPI网络以及构建“茯苓-半夏”-活性成分-靶点-疾病网络;运用DAVID数据库进行GO和KEGG富集分析;采用Autodock Tools1.5.6工具进行分子对接研究。结果 本文以“茯苓-半夏”作为核心药对,共筛选得到28个活性成分,其中涉及抑郁症作用靶点的中药活性成分有23个,如松柏苷、常春藤素、曲美烯酸、β-谷甾醇等,涉及抑郁症作用靶点14个,分别为ALB、MAOB、MAPK14、GSTP1、AKR1B1、CASP3、PPARG、AR、ESR1、HSD11B1、TNNC1、GBA、IMPA1、TTR。主要涉及生物学进程的信号转导(signal transduction)、对雌激素的反应(response to estrogen)、对雌二醇的反应(response to estradiol)、对甲状腺激素的反应(response to thyroid hormone)等,KEGG的通路包括癌症的途径(Pathways in cancer)、癌症中的蛋白多糖(Proteoglycans in cancer)、肌萎缩侧索硬化症(Amyotrophic lateral sclerosis)。分子对接验证结果均≤-5.0(k J/mol),表明靶点与成分的结合活性良好。结论 本文探讨了“茯苓-半夏”干预抑郁症多成分-多靶点-多通路的作用特点,其中MAOB是胺氧化酶[含黄素]B在中枢神经系统和外周组织中神经活性胺和血管活性胺的代谢中具有重要作用,MAOB优先降解苄胺和苯乙胺,可能具有直接发挥抗抑郁作用,为今后临床应用和基础研究提供了一定的思路和参考。

Objective This paper uses the methods of network pharmacology and molecular docking to study the mechanism of "tuckahoe-pinellia ternata" in the intervention of depression, in order to support basic research and clinical application.Methods TCMSP, pubChem and pharmmapper databases are used to search and screen the active components and action targets of "tuckahoe-pinellia ternata". After that, Drugbank, GeneCards and OMIM databases are used to screen the disease targets related to depression, and the intersection targets of the two are acquired;The protein-protein interaction relationship is obtained from STRING11.5 database, and the PPI network and " tuckahoe-pinellia ternata"-active ingredient-target-disease network are constructed by using Cytoscape3.8.2 software;DAVID database is used for GO(Gene Ontology) and KEGG(Kyoto Encyclopedia of genes and genes) enrichment analysis;Autodock tools1.5.6 is used for molecular docking research.Results In this paper, "tuckahoe-pinellia ternata" was selected as the main drug pair, and a total of 28 active components were screened, including 23 active components of traditional Chinese medicine related to the target of depression, such as coniferin, ivy essence, trimeric acid, β-Sitosterol, etc., involved in 14 depression targets, including ALB, MAOB, MAPK14, GSTP1, AKR1B1, CASP3, PPARG, AR, ESR1, HSD11B1, TNNC1, GBA, IMPA1 and TTR. This paper mainly involves signal transduction of biological process, response to estrogen, response to estradiol, response to thyroid hormone, etc. KEGG pathways include pathways in cancer, proteoglycans in cancer, and amyotrophic lateral sclerosis. The results of molecular docking validation were ≤-5.0(kJ/mol), indicating the good binding activity between the target and the component.Conclusion This paper discusses the features of "tuckahoe-pinellia ternata" in the depression intervention of multiple components-multiple targets-multiple pathways. It can be found that MAOB[containing flavin] plays an important role in the metabolism of neuroactive amines and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine, which may have a direct antidepressant effect. It provides some ideas and references for future clinical application and basic research, which is of great significance.