基于网络药理学和分子对接技术分析逍遥散治疗斑秃的作用机制

Analysis of the Action Mechanism of Xiaoyao San in the Treatment of Alopecia Areata Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学及分子对接的方法研究逍遥散治疗斑秃的作用机制。方法：于TCMSP数据库中，根据ADME筛选，得到逍遥散中8味中药柴胡、当归、白芍、薄荷、茯苓、白术、生姜、甘草的有效成分及作用靶点，以Pharm Mapper补充预测相关靶点，从OMIM、Genecards、Drugbank、TTD数据库中获取斑秃相关靶点，得到二者共有靶点，使用Cytoscape3.9.1软件构建药物成分-靶点网络图。基于STRING数据库构建蛋白质相互作用(PPI)网络，利用Cytoscape3.9.1进行可视化分析。利用Metascape数据库对靶点进行富集分析并进行可视化。将得到的关键成分及靶点利用Autodockvina 1.2.3进行分子对接验证。结果：得到逍遥散作用于斑秃的核心成分104个，包括槲皮素、木犀草素、山奈酚、阿卡西汀、刺芒柄花素、芦荟大黄素、异鼠李素、甘草查尔酮B等；核心靶点36个，包括PTGS2、NOS2、CDK2、TNF、IL6、IL1B、IFNG、CXCL8等；蛋白相互作用共涉及2958个生物学过程，157条通路，分子对接验证提示连接度最高的前8位核心成分与靶点蛋白结合性能良好。结论：逍遥散治疗斑秃的机制可能通过PTGS2、NOS2、CDK2、TNF、IL6、IL1B、IFNG、CXCL8等关键蛋白起效，过程涉及免疫调节。

Abstract: Objective: To investigate the mechanism of action of Xiaoyao San in the treatment of alopecia areata (AA) based on network pharmacology and molecular docking methods. Methods: The active ingredients and action targets of eight Chinese herbs, namely Chai Hu, Dang Gui, Bai Shao, Bo He, Fu Lin, Bai Zhu, Sheng Jiang and Gan Cao, were obtained from the TCMSP database based on ADME screening, and the relevant targets were predicted by Pharm Mapper supplementation. The AA’s targets were obtained from OMIM, Genecards, Drugbank and TTD databases to obtain the targets common to both, and the drug component-target network map was constructed using Cytoscape 3.9.1 software. Construct a protein interaction (PPI) network based on the STRING database and use Cytoscape 3.9.1 for visualisation and analysis. Enrichment analysis of targets was performed and visualised using the Metascape database. The key components and targets obtained were validated by molecular docking using Autodock vina1.2.3. Results: 104 core components were obtained for the action of prolotherapy in AA, including quercetin, lignan, kaempferol, acacetin, prickly mangosteen, aloe rhodopsin, isorhamnetin and glycyrrhiza chalcone B. 36 core targets were obtained, including PTGS2, NOS2, CDK2, TNF, IL6, IL1B, IFNG, CXCL8; the protein interactions involved a total of 2958 biological processes and 157 pathways were involved in the protein interactions. The molecular docking validation indicated that the top 8 core components with the highest degree of connectivity had good binding performance to the target proteins. Conclusion: The mechanism of Xiaoyao San for AA may work through key proteins such as PTGS2, NOS2, CDK2, TNF, IL6, IL1B, IFNG and CXCL8, and the process involves immune regulation.