蒙药安神补心六味丸抗抑郁作用网络药理学机制研究

Mechanism of antidepressant effect of Ansheng Buxin Liuwei pills based on network pharmacology

目的应用网络药理学、分子对接技术、体外实验技术,预测以及验证蒙药安神补心六味丸的抗抑郁药理作用机制。方法TCMSP数据库及文献挖掘获取安神补心六味丸的活性成分,SwissTargetPrediction预测成分相关靶点信息,Cytoscape构建药材-成分-靶点网络。通过GeneCards、Drugbank、OMIM等数据库检索抑郁症靶点。STRING数据库获取蛋白相互作用关系网络信息。DAVID数据库进行GO生物过程富集分析和KEGG信号通路富集分析。Autodock vina软件进行分子对接验证。BV2小胶质细胞建立体外损伤模型,CCK-8法检测细胞活力,qPCR法检测相关核心靶点mRNA表达量。结果筛选出安神补心六味丸活性成分34个,涉及140个潜在作用靶点,筛选核心靶点59个,共涉及99条信号通路;分子对接结果显示桦木酸、豆甾醇、β-谷固醇、槲皮素等10种活性成分与AKT1、APP、ALB、MAPK3、VEGFA、MAPK1靶点均拥有良好的结合能力。体外实验结果表明,经给药后,BV2细胞活力较模型组明显上升。安神补心六味丸可调节各核心靶点mRNA的表达。结论安神补心六味丸可能主要通过羟色胺突触等信号通路以及相关核心靶点来发挥抗抑郁作用。

Aim To apply network pharmacology,molecular docking,and in vitro experimental techniques to predict as well as verify the antidepressant pharmacological mechanisms of Mengyao Anshen Buxin Liuwei pills.Methods TCMSP database and literature mining were used to obtain the active ingredients of Anshen Buxin six flavor pills,SwissTargetPrediction was applied to predict the ingredient related target information,and Cytoscape was employed to construct a medicinal herb ingredient target network.Depression targets were retrieved through GeneCards,Drugbank,OMIM and other databases.STRING database was used to obtain protein interaction relationship network information.DAVID database was used for GO biological process enrichment analysis and KEGG signaling pathway enrichment analysis.Autodock vina software was applied for molecular docking validation.In vitro injury model was established in BV2 microglial cells,cell viability was assessed by CCK-8 assay,and the mRNA expression of relevant core targets was assessed by qPCR.Results A total of 34 active components of Anshen Buxin Liuwei pills were screened,involving 140 potential targets and 59 core targets,involving 99 signaling pathways.Molecular docking results showed that betulinic acid,stigmasterolβ-stiosterol 10 active components such as sitosterol and quercetin had good binding ability with AKT1,APP,ALB,MAPK3,VEGFA and MAPK1 targets.The results in vitro showed that the activity of BV2 cells increased significantly compared with the model group.Anshen Buxin Liuwei pills could regulate the mRNA expression of each core target.Conclusion Anshen Buxin Liuwei pills may play an antidepressant role mainly through serotonin synaptic and other signaling pathways and related core targets.