基于网络药理学和分子对接技术对木香顺气丸治疗抑郁症的作用机制分析

Mechanism Analysis of Muxiang Shunqi Pills in Treating Depression Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：运用网络药理学和分子对接技术分析木香顺气丸的有效化学成分、作用靶点来揭示相关的信号通路产生抗抑郁效果的作用机制。方法：利用中药系统药理学数据库与分析平台(TCMSP)和中药分子机制生物信息学分析工具库(BATMAN-TCM)获取木香顺气丸的有效成分及靶点信息，从PharmGKB、Genecards、OMIM、TTD和DrugBank五个疾病数据库中获取抑郁症的关键基因靶点，再通过Uniport数据库对靶点基因名进行校对，获得药物–疾病共有靶点，采用String数据库构建蛋白互相作用网络(PPI)，Cytoscape3.8.0软件构建成分–靶点–疾病网络，进行可视化及拓扑学分析，筛选出木香顺气丸治疗抑郁症的核心靶点。应用DAVID数据库和R Studio软件对药物和疾病的交集靶点进行GO富集和KEGG通路分析，再根据网络分析结果筛选活性成分和关键靶点，最后利用AutoDock Tools分子对接软件对活性成分与关键抗抑郁靶点进行结果验证。结果：最终筛选出木香顺气丸有效化学成分250个，对应的药物靶点1838个，药物–疾病共有靶点426个。从构建的PPI网络和模块分析中发现AKT1、INS、ALB、BDNF、TP53、IL6、TNF、VEGFA、IL1B和ESR1这10个基因靶点可能是关键靶点。通过GO富集分析和KEGG通路分析发现木香顺气丸发挥抗抑郁作用的主要通路有神经活性配体受体相互作用信号通路、癌症通路、神经退行性变的途径——多种疾病、cAMP信号通路和钙信号通路。最后通过分子对接显示，ALB和白桦脂醇、ALB和槲皮素、BDNF和槲皮素以及BDNF和伞形酮的结合能力最好，这也说明ALB、BDNF可能与白桦脂醇、槲皮素、伞形酮结合产生抗抑郁的效果。结论：可以初步预测木香顺气丸具有一定的抗抑郁功效，并且是通过多成分、多靶点、多通路共同作用的分子机制来治疗抑郁症，为深入探究木香顺气丸抗抑郁的作用特点以及阐明其药理机制提供依据。

Abstract: Objective: To analyze the active chemical composition and action target of Muxiang Shunqi Pills by network pharmacology and molecular docking technology to reveal the mechanism of action of the relevant signaling pathways to produce antidepressant effect. Methods: The active ingredients and targets of Muxiang Shunqi Pills were obtained by using the Chinese Medicine Sys-tem Pharmacology Database and Analysis Platform (TCMSP) and the Molecular Mechanism Bioin-formatics Analysis Tool Library of Chinese Medicines (BATMAN-TCM), and the key gene targets of depression were obtained from the five disease databases of PharmGKB, Genecards, OMIM, TTD and Drug Bank, the gene names of the targets were then proofread through the Uniport database, and the drug-disease common targets were obtained, and the String database was used to construct the protein interaction network (PPI), and the Cytoscape3.8.0 software was used to construct the com-ponent-target-disease network, visualize and topology analysis, and the core targets of muxiang-shunqi pills for the treatment of depression were screened. The DAVID database and RStudio soft-ware were used to conduct GO enrichment and KEGG pathway analysis for the intersection targets of drugs and diseases. And then active ingredients and key targets were screened according to net-work analysis results. Finally, AutoDock Tools molecular docking software was used to verify the results of the active ingredient and key antidepressant targets. Results: Finally, 250 active chemical components of Muxiang Shunqi Pills were screened, 1838 corresponding drug targets, and 426 drug-disease targets. From the analysis of the built PPI network and module, it was found that the 10 gene targets of AKT1, INS, ALB, BDNF, TP53, IL6, TNF, VEGFA, IL1B and ESR1 may be key targets. Through GO enrichment analysis and KEGG pathway analysis, it was found that the main pathways for Muxiang Shunqi pills to exert antidepressant effects were neuroactive ligand receptor interac-tion signaling pathway, cancer pathway, neurodegenerative pathway—a variety of diseases, cAMP signaling pathway and calcium signaling pathway. Finally, through molecular docking, it was shown that ALB and Betulin, ALB and quercetin, BDNF and quercetin and BDNF and Umbelliferone had the best binding capacity, which also said that ALB and BDNF could be combined with Betulin, quercetin, and Umbelliferone to produce antidepressant effects. Conclusion: It can be preliminarily pre-dicted that Muxiang Shunqi Pills has a certain antidepressant effect, and it is treated by the molec-ular mechanism of multi-component, multi-target and multi-pathway interaction, which provides a basis for in-depth exploration of the antidepressant characteristics of Muxiang Shunqi Pills and elu-cidating its pharmacological mechanism.