基于网络药理学探讨鱼油抗抑郁作用机制

Mechanism of Antidepressant Action of Fish Oil Based on Network Pharmacology

目的:运用网络药理学的方法探讨鱼油抗抑郁的作用机制。方法:通过PharmMapper、SwissTargetPrediction、DrugBank、GeneCards以及Disgenet等数据库获得鱼油治疗抑郁症的作用靶点;利用String网站与Cytoscape软件获得蛋白互作网络分析;通过DAVID 6.8数据库对潜在作用靶点进行富集分析;使用Cytoscape软件绘制成分靶点通路可视化网络图。结果:鱼油主要通过EPA与DHA发挥抗抑郁作用,其治疗抑郁症的相关靶点共115个,主要为MAPK3、MAPK1、CASP3、PPARG、PPARA、PTGS2、DRD2等。这些核心靶点作用于5-羟色胺能突触通路、PPAR信号通路、花生四烯酸代谢通路等信号通路、神经活性配体-受体相互作用信号通路,调节对药物的反应、类固醇激素介导的信号通路、氧化-还原过程等生物过程,发挥抗抑郁作用。结论:鱼油有助于治疗抑郁症具有多靶点、多通路的特点,可能通过5-羟色胺能突触通路、PPAR信号通路、神经活性配体-受体相互作用信号通路、花生四烯酸代谢通路等发挥抗抑郁作用。

Objective:To investigate the anti-depression mechanisms of fish oil by using network pharmacology.Methods:The targets for the treatment of depression with fish oil were obtained from databases such as the PharmMapper,SwissTargetPrediction,DrugBank,GeneCards,and Disgenet.The potential targets protein interaction network was analyzed using String website and Cytoscape software.Enrichment analysis of potential target proteins was performed using the DAVID 6.8 database.Additionally,a visual network diagram of the component-target pathway was created using Cytoscape software.Results:Fish oil exhibited anti-depression effects mainly through EPA and DHA.A total of 115 relevant targets for the treatment of depression were identified,including MAPK3,MAPK1,CASP3,PPARG,PPARA,PTGS2,DRD2,among others.These main targets play an anti-depressant role via regulating signal pathways,such as serotonergic synapse,PPAR signaling pathway,arachidonic acid metabolism,neuroactive ligand-receptor interaction and influencing biological processes,such as response to drug,steroid hormone mediated signaling pathway,oxidation-reduction process.Conclusion:Fish oil treatment for depression is characterized by its action on multiple targets and pathways,potentially involving the serotonergic synapse,PPAR signaling pathway,neuroactive ligand-receptor interaction,and arachidonic acid metabolism pathways to exert its anti-depressant effects.