基于网络药理学和分子对接探讨参芪五味子胶囊治疗焦虑症的机制

Exploration of the mechanism of Shenqi Wuweizi Capsule in treating anxiety disorder based on network pharmacology and molecular docking

关键词:  参芪五味子胶囊  焦虑症  网络药理学  分子对接  机制研究

Key words:  Shenqi Wuweizi Capsule  anxiety disorder  network pharmacology  molecular docking  mechanism study

摘要:

[目的] 通过网络药理学和分子对接技术探讨参芪五味子胶囊治疗焦虑症的作用机制。[方法] 利用中药系统药理学数据库与分析平台（TCMSP）预测和筛选参芪五味子胶囊的主要生物活性成分及其靶点，与GeneCards、OMIM、DisGeNET、TTD数据库检索筛选出的焦虑症疾病靶点交集整合；借助String平台绘制蛋白质相互作用（PPI）网络，并开展基因本体（GO）注释功能与京都基因与基因组百科全书（KEGG）通路富集分析；依托Cytoscape软件绘制“药物-成分-靶点”以及“成分-靶点-通路”的网络关系图；采用Autodock分子对接技术将关键靶点与参芪五味子胶囊中关键活性成分进行验证。[结果] 获得成分靶点238个，疾病靶点919个，交集靶点62个，通过CytoNCA插件筛选出19个核心靶点；GO分析表明，主要涉及信号转导、基因表达正调控、同种蛋白结合、细胞外配体门控离子通道活性、苯二氮卓类受体活性等；KEGG分析表明，主要富集通路涵盖AGE-RAGE信号通路、神经活性配体-受体相互作用通路、流体剪切应力和动脉粥样硬化通路等；分子对接显示，36组关键靶点与活性成分组合结合能均小于-20.92 kJ/mol，证明结合良好。[结论] 参芪五味子胶囊可通过多成分-多靶点-多通路发挥治疗焦虑症的作用，为后续探究参芪五味子胶囊治疗焦虑症提供研究思路。

Abstract:

[Objective] To explore the mechanism of Shenqi Wuweizi Capsule in the treatment of anxiety disorder through network pharmacology and molecular docking technology. [Methods] TCMSP database was used to predict and screen the main bioactive ingredients and their targets of Shenqi Wuweizi Capsule，and integrate with the targets of anxiety disorders which were selected by GeneCards，OMIM，DisGeNET and TTD database. The protein-protein interaction（PPI） network was mapped with String platform，and the gene ontology（GO） annotation function and the Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were carried out. Make the network diagram of “drug-composition-target” and “composition-target-pathway” based on Cytoscape software；The Autodock molecular docking technique was used to verify the key target and the key active ingredients in Shenqi Wuweizi Capsule. [Results] The 238 component targets，919 disease targets and 62 intersection targets were obtained，and 19 core targets were selected by CytoNCA plug-in. GO analysis showed that it mainly involved in signal transduction，positive regulation of gene expression，isoprotein binding，extracellular ligand-gated ion channel activity，benzodiazepine receptor activity，etc. KEGG analysis showed that the main enrichment pathways included AGE-RAGE signaling pathway，neuroactive ligand-receptor interaction pathway，fluid shear stress and atherosclerosis pathway. Molecular docking showed that the binding energy of 36 groups of key targets and active ingredients was less than -20.98 kJ/mol，which proved that the binding was good. [Conclusion] Shenqi Wuweizi Capsule can play a role in the treatment of anxiety disorder through multi-component，multi-target and multi-pathway，providing research ideas for the follow-up study of Shenqi Wuweizi Capsule in the treatment of anxiety disorder.