基于网络药理学酸枣仁生物碱抗抑郁作用机制的研究

Study on antidepressant mechanism of Ziziphi Spinosae Semen alkaloid based on network pharmacology

目的:采用网络药理学方法预测酸枣仁生物碱抗抑郁的作用机制。方法:首先挖掘相关的数据库如TCMSP、TCMDatabase@Taiwan、Drug Bank、Pharm Mapper、DAVID等,获得酸枣仁生物碱的主要成分和生物碱抗抑郁的潜在作用靶点,并对潜在靶点进行KEGG通路和GO分析。进一步采用软件Cytoscape构建并分析“成分-靶点-通路”生物网络图,最终从整体角度预测酸枣仁生物碱抗抑郁的作用机制。结果:酸枣仁生物碱抗抑郁的主要成分包括荷叶碱(nuciferine)、原荷叶碱(nornuciferine)、右旋衡州乌药碱(coclaurine)、木兰花碱(magnoflorine),主要作用于钙调蛋白(CALM1)、表皮生长因子受体(EGFR)、糖原合成酶激酶-3β(GSK3B)、视黄酸受体(RXRA)等靶点,涉及并影响磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)、钙离子等信号通路以及丝裂原活化蛋白激酶(MAPK)级联、蛋白结合等生物进程,发挥抗抑郁作用。结论:初步预测获得酸枣仁生物碱抗抑郁作用机制,多成分-多靶点-多通路的特点符合中医整体综合作用理念。

Objective:To explore the anti-depression mechanism of total alkaloids from Ziziphi Spinosae Semen(ZSS)based on network pharmacology.Methods:First,major components and potential anti-depressant targets of ZSS alkaloids were obtained by mining relevant databases such as TCMSP,TCMDatabase@Taiwan,Drug Bank,Pharm Mapper,DAVID,etc.KEGG pathway and GO analysis were performed on the potential targets.Furthermore,the software Cytoscape was used to construct and analyze the biological network diagram of"component-target-pathway".Finally,the anti-depressive mechanism of ZSS alkaloids was predicted from an overall perspective.Results:It was predicted that the main anti-depressant components of ZSS alkaloids included nuciferine,nornuciferine,coclaurine and magnoflorine,which played an anti-depressant role mainly by acting on the targets of calmodulin-1(CALM1),epidermal growth factor receptor(EGFR),glycogen synthase kinase-3 beta(GSK3B)and retinoic acid receptor RXR-alpha(RXRA),influencing phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt)and calcium signaling pathways as well as mitogen-activated protein kinase(MAPK)cascade and protein binding biological processes.Conclusion:The antidepressant mechanism of ZSS alkaloids is preliminarily predicted,and the characteristics of multi-component,multi-target and multi-pathway are consistent with the concept of integrated action of traditional Chinese medicine.