运用网络药理学探讨开心散治疗抑郁症的作用机制

Using Network Pharmacology Model to Explore the Mechanism of Kai-Xin-San in Treating Depression

目的本研究旨在运用网络药理学方法,预测开心散活性成分的抗抑郁药理作用机制。方法通过TCMSP、ETCM获取开心散的成分和靶点,运用Genecard、OMIM筛选抑郁症相关的蛋白,通过STRING构建蛋白相互作用网络,使用Cytoscape进行靶点的拓扑分析、MCODE聚类分析,使用R语言进行GO和KEGG通路富集分析,最后使用MOE软件进行分子对接验证。结果网络分析表明,开心散中25个活性成分与其发挥抗抑郁作用密切相关,该机制涉及到51个靶点(包括ACHE、HTR3A、DRD2等)以及24条通路;分子对接结果显示化合物aposcopolamine、perlolyrine、hederagenin与PPARG、ACHE、SLC6A4、DRD2靶点均具有较好的结合能力。结论开心散可能主要通过神经活性受体配体相互作用、羟色胺突触、cAMP通路等相关靶标起到抗抑郁的功效,该研究为一步揭示开心散治疗抑郁症的潜在活性成分及其可能的作用机制提供了思路。

Objective To predict the anti-depressant pharmacological mechanism of Kai-Xin-San(KXS)active ingredients by network pharmacology.Methods The components and targets of KXS were obtained by TCMSP and ETCM,and the proteins related to depression were screened by Genecard and OMIM.The protein interaction network(PPI)was constructed by STRING.Topological attribute analysis and MCODE cluster analysis of the target were performed by Cytoscape.R language was performed to conduct GO and KEGG path enrichment analysis.Finally,MOE software was applied for molecular docking verification.Results Network analysis showed that the 25 active ingredients in KXS were closely related to its anti-depressant effect.The mechanism involved 51 targets(ACHE,HTR3 A,and DRD2,etc.)and 24 pathways.The molecular docking showed that aposcopolamine,perlolyrine,and hederagenin had good docking activity with PPARG,ACHE,SLC6 A4,and DRD2,respectively.Conclusion KXS may exert anti-depressant effects through pathway-related targets such as neuroactive receptor-ligand interactions,serotonin synapses,and c AMP pathways efficacy.This study provides an idea for the study of the potential active components of KXS in the treatment of depression and its possible mechanism of action.