基于网络药理学探讨阿朴菲类生物碱抗抑郁的作用机制  

Exploring the antidepressant mechanism of aporphine alkaloids based on network pharmacology

作　　者：王志慧 乔卫[1] WANG Zhi-hui;QIAO Wei(Department of Natural Medicines,College of Pharmacy,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学药学院天然药物学系,天津300070

出　　处：《天津医科大学学报》2022年第6期591-597,共7页Journal of Tianjin Medical University

摘　　要：目的:采用网络药理学结合分子对接的方法预测阿朴菲类生物碱抗抑郁作用机制。方法:首先通过CNKI、Pubmed、CAS、Swiss Target Prediction等数据库获得阿朴菲类生物碱代表性成分和生物碱抗抑郁的潜在作用靶点。对生物碱成分与抑郁症交集靶点进行GO和KEGG分析。采用Cytoscape软件构建蛋白相互作用(PPI)网络图和成分-靶点-通路网络图并利用分子对接进一步验证其相互作用。结果:阿朴菲类生物碱代表性成分主要包括莲碱(roemerine)、蝙蝠葛林碱(menisperine)、无根藤新碱(cassythicine)等,作用于N-甲基-D-天冬氨酸受体亚基基因(GRIN1)、5-羟色胺(5-HT)转运蛋白(SLC6A4)、儿茶酚氧位甲基转移酶基因(COMT)等靶点。涉及神经活性配体-受体相互作用信号通路、5-羟色胺能突触以及cAMP信号通路等发挥抗抑郁作用。结论:初步预测了阿朴菲类生物碱抗抑郁作用机制,揭示了其多靶点、多通路整合作用的结果。Objective:Network pharmacology combined with molecular docking method was used to predict the antidepressant mechanism of aporphinealkaloids.Methods:First,the representative constituents and potential anti-depressant targets of aporphine alkaloids were obtained through databases such as CNKI,Pubmed,CAS and Swiss Target Prediction.GO analysis and KEGG pathway analysis were performed on the intersection targets of alkaloid components and depression.The protein interaction(PPI)network diagram and component-target-pathway network diagram were constructed by Cytoscape software,and molecular docking was used to further verify their interactions.Results:The representative components of the aporphine alkaloids mainly include roemerine,menisperine,and cassiythicine,which act on targets such as N-methyl-D-aspartate receptor subunit gene(GRIN1),5-hydroxytryptamine(5-HT)transporter(SLC6A4),catechol oxygen methyltransferase gene(COMT).Pathways involved in neuroactive ligand-receptor interaction,serotonergic synapse,and cAMP signaling pathway exert antidepressant effects.Conclusion:The antidepressant mechanism of aporphine alkaloids is initially predicted and the results of its multi-target and multi-pathway integrative effects are revealed.

关 键 词：网络药理学 阿朴菲类生物碱 抗抑郁 通路分析 

分 类 号：R971.43[医药卫生—药品]