基于网络药理学与分子对接技术探讨散偏汤治疗偏头痛的作用靶点与分子机制

Exploring the targets and molecular mechanisms of San Miguel Tang in the treatment of migraine based on network pharmacology and molecular docking techniques

关键词:  散偏汤  偏头痛  网络药理学  靶点  信号通路  分子对接

Key words:  San Miguel Tang  migraine  network pharmacology  target  signaling pathway  molecular docking

摘要:

[目的] 运用网络药理学方法与分子对接技术预测散偏汤治疗偏头痛(migraine)的作用机制。[方法] 利用TCMSP数据库对散偏汤进行活性成分筛选。通过STRING 11.5数据库构建蛋白互作网络,并得到药物靶向基因;通过OMIM、GeneCards数据库筛选偏头痛的疾病靶点基因;利用Rx64 4.1.1软件构建韦恩图,得到散偏汤治疗偏头痛的潜在靶点,进行GO及KEGG富集分析并制作气泡图,相关结果用Cytoscape 3.7.1构建"药物-成分-疾病-通路"网络,并进行可视化研究。利用 PyMOL和AutoDock Vina等软件对散偏汤活性成分与核心靶蛋白进行分子对接。[结果] 散偏汤治疗偏头痛的核心活性成分为槲皮素、木犀草素、山奈酚等,潜在治疗靶点主要包括PTGS2、MAPK1、MAPK3、GSK3β、AKT1、HSP90AA1、ESR1等,主要涉及脂质和动脉硬化、AGE-RAGE、PI3K-Akt、IL-17、TNF、MAPK等信号通路。分子对接结果显示,槲皮素、木犀草素和山奈酚与关键核心靶点PTGS2、MAPK1、MAPK3有较好的结合力。[结论] 通过网络药理学研究,初步预测了散偏汤治疗偏头痛的作用机制可能主要与调节炎症因子,改善神经源性炎症相关,也能够起到调节免疫功能与激素水平、维持血管稳态等作用,体现了中药方剂"多成分-多靶点-多通路"的药效作用特点,为后续临床应用与研究提供理论参考。

Abstract:

[Objective] Predicting the mechanism of action of San Miguel Tang in the treatment of migraine using network pharmacology methods and molecular docking techniques.[Methods] Screening of active ingredients in San Miguel Tang using the TCMSP database. Constructing protein interaction networks and obtaining drug-targeted genes from the STRING 11.5 database. Screening for disease target genes in migraine through OMIM,GeneCards databases. Using Rx64 4.1.1 software to construct Venn diagrams and obtain potential targets for the treatment of migraine with San Miguel Tang,GO and KEGG enrichment analyses were performed and bubble maps were created,and the related results were used to construct a "drug-component-disease-pathway" network using Cytoscape 3.7.1 and visualized. Molecular docking of the active ingredients of San Miguel Tang to the core target proteins was performed using software such as PyMOL and AutoDock Vina.[Results] The core active ingredients of San Miguel Tang for the treatment of migraine are quercetin,lignan and kaempferol. The potential therapeutic targets mainly include PTGS2,MAPK1,MAPK3,GSK3β,AKT1,HSP90AA1 and ESR1,which are mainly involved in lipid and atherosclerosis,AGE-RAGE,PI3K-Akt,IL-17,TNF,MAPK and other signalling pathways. Molecular docking results showed that quercetin,lignan and kaempferol bound well to the key core targets PTGS2,MAPK1 and MAPK3.[Conclusion] Through the network pharmacological study,it was initially predicted that the mechanism of action of San Miguel Tang in the treatment of migraine might be mainly related to the regulation of inflammatory factors and improvement of neurogenic inflammation,as well as the regulation of immune function and hormone levels and the maintenance of vascular homeostasis,reflecting the "multi-component-multi-target-multi-pathway" pharmacological characteristics of the Chinese medicine formula,providing theoretical reference for subsequent clinical application and research.