基于网络药理学与分子对接研究肉豆蔻治疗抑郁症的作用机制

Mechanism of action of Myristica fragrans in treatment of depression: A study based on network pharmacology and molecular docking

目的:基于网络药理学方法与分子对接技术研究肉豆蔻治疗抑郁症的作用机制。方法:通过中药系统药理学分析平台TCMSP,获得肉豆蔻的活性成分和作用靶点;利用Uniprot数据库构建中药-成分-靶点网络;从GeneCards、OMIM、DrugBank数据库获得抑郁症疾病靶点、肉豆蔻及抑郁症共有靶点;通过Venny 2.1.0平台、String平台进行肉豆蔻与抑郁症共同靶点相互作用分析;利用Cytoscape 3.7.2软件构建蛋白互作(PPI)网络,采用Metascape平台对核心靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析;采用分子对接技术确定肉豆蔻有效成分作用于抑郁症的核心靶点。结果:获得42个潜在作用靶点。乙酰胆碱酯酶(ACHE)、钠依赖性血清素转运体(SLC6A4)、一氧化氮合酶(NOS3)、Alpha-2A肾上腺素能受体(ADRA2A)可能是肉豆蔻治疗抑郁症的核心基因。肉豆蔻作用于抑郁症的通路涉及神经受体相互作用、钙信号通路。分子对接技术验证了肉豆蔻有效成分中的β-谷甾醇与潜在靶点ACHE和NOS3具有较好的结合活性。结论:肉豆蔻的主要活性成分β-谷甾醇可能通过作用于ACHE等多个靶点来调控神经受体相互作用、钙信号通路等多条信号通路,从而发挥抗抑郁作用。

Objective: To investigate mechanism of action of Myristica fragrans in the treatment of depression based on network pharmacology and molecular docking.Methods: TCMSP platform was used to obtain the active components and action targets of Myristica fragrans, and Uniprot database was used to establish a traditional Chinese medicine-component-target network.GeneCards, OMIM,and DrugBank databases were used to obtain the disease targets of depression and the common targets of Myristica fragrans and depression.Venny 2.1.0 platform and String platform were used to analyze the interaction between the common targets of Myristica fragrans and depression.Cytoscape 3.7.2 software was used to establish a protein-protein interaction network, and Metascape platform was used to perform gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of core targets.The molecular docking technique was used to determine the core targets for the effective constituents of Myristica fragrans to act on depression.Results: A total of 42 potential action targets were obtained.Acetylcholinesterase(ACHE),sodium-dependent serotonin transporter(SLC6 A4),nitric oxide synthase 3(NOS3),and alpha-2 a adrenergic receptor(ADRA2 A) were the core genes in the treatment of depression by Myristica fragrans.The action of Myristica fragrans on depression involved the pathways of neuroreceptor interaction and calcium signal.Molecular docking results showed that the effective constituent beta-sitosterol of Myristica fragrans had a good binding activity to the potential targets ACHE and NOS3.Conclusion: The main effective constituent beta-sitosterol of Myristica fragrans regulates multiple signaling pathways including neuroreceptor interaction and calcium signal by acting on multiple targets including ACHE,thereby exerting an antidepressive effect.