基于网络药理学和分子对接技术探讨茯苓-酸枣仁药对治疗广泛性焦虑障碍的作用机制  

Mechanism of action of Poria cocos-Semen Ziziphi Spinosae drug combination in treatment of generalized anxiety disorder:A study based on network pharmacology and molecular docking

作　　者：赵俊霞 赵睿婷 朱应怀 张科[2] 袁恒杰[1,2] ZHAO Junxia;ZHAO Ruiting;ZHU Yinghuai;ZHANG Ke;YUAN Hengjie(Tianjin Medical University General Hospital Airport Hospital,Tianjin 300308,China;Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院空港医院,天津300308 [2]天津医科大学总医院,天津300052

出　　处：《湖南中医杂志》2024年第11期165-173,共9页Hunan Journal of Traditional Chinese Medicine

摘　　要：目的:利用网络药理学和分子对接技术探讨茯苓-酸枣仁药对治疗广泛性焦虑障碍(GAD)的作用机制。方法:以化合物的口服生物利用度(OB)和类药性(DL)为标准,依据中药药理学技术平台(TCMSP)数据库、小分子靶点预测平台(SwissTargetPrediction)预测和筛选茯苓、酸枣仁的活性成分和靶点,利用GeneCards数据库筛选治疗GAD的作用靶点,并通过Cytoscape 3.7.2软件构建茯苓-酸枣仁的蛋白质-蛋白质相互作用(PPI)网络,筛选核心靶点,使用Metascape数据库进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,推断其作用机制。运用AutoDock Vina和PyMOL软件对茯苓-酸枣仁药对主要活性成分和关键靶点进行分子对接验证。结果:共筛选出15个茯苓活性成分,9个酸枣仁活性成分,与GAD有85个交集靶点,筛选出多巴胺-2受体,5-羟色胺等10个关键靶点;参与调节神经活性配体-受体相互作用、5-羟色胺能突触、多巴胺能突触等关键代谢通路;参与信号传导、内分泌代谢、循环系统调节等多种生物过程。分子对接结果显示,筛选出的4位活性成分与关键靶点对接结果均≤-4.25 kcal/mol,提示药物活性成分与关键交集靶点有较好的结合活性。结论:茯苓-酸枣仁可能通过调控DRD2,ESR1,HTR2A等靶点,调节神经活性配体-受体相互作用等通路发挥抗焦虑的作用,为茯苓-酸枣仁配伍治疗GAD作用机制的研究提供参考。Objective:To investigate the mechanism of action of Poria cocos-Semen Ziziphi Spinosae drug combination in the treatment of generalized anxiety disorder(GAD)based on network pharmacology and molecular docking.Methods:With oral bioavailability and drug-likeness as the standard,TCMSP database and SwissTarget Prediction platform were used to predict and identify the active components and targets of Poria cocos and Semen Ziziphi Spinosae,and GeneCards database was used to identify the action targets for the treatment of GAD.Cytoscape 3.7.2 software was used to establish a protein-protein interaction network for Poria cocos-Semen Ziziphi Spinosae and identify the core targets.Metascape database was used to perform GO functional enrichment a-nalysis and KEGG pathway enrichment analysis and predict the mechanism of action of the drug combination.AutoDock Vina and PyMOL were used to perform molecular docking validation for the main active components and key targets of the Poria cocos-Semen Ziziphi Spinosae drug combination.Results:A total of 15 active compo-nents of Poria cocos and 9 active components of Semen Ziziphi Spinosae were obtained,with 85 intersecting targets with GAD,and 10 key targets were obtained,including dopamine-2 receptor and 5-hydroxytryptamine,which were involved in the key metabolic pathways for regulating neuroactive ligand-receptor interaction,5-hydroxytryptamine synapses,and dopaminergic synapses,as well as various biological processes for signal transduction,endocrinology and metabolism,and circulatory system regulation.Molecular docking showed a binding energy of≤-4.25 kcal/mol between the 4 active components and the key targets obtained,suggesting that there was a relatively good bind-ing activity between the active components of drugs and the key intersecting targets.Conclusion:Poria cocos-Semen Ziziphi Spinosae exerts a therapeutic effect on anxiety by regulating the targets such as DRD2,ESR1,and HTR2A and the pathways such as neuroactive ligand-receptor interaction,which provides a referen

关 键 词：广泛性焦虑障碍 茯苓-酸枣仁 网络药理学 分子对接技术 作用机制 

分 类 号：R277.79[医药卫生—中医学]