网络药理学结合分子对接技术揭示芹菜籽抑制痛风的潜在分子机制

Potential molecular mechanism of celery seed in gout treatment of network pharmacology with molecular docking

目的:运用网络药理学和分子对接研究芹菜籽抑制或治疗痛风的分子机制。方法:利用TCMSP数据库等在线靶点筛选平台收集芹菜籽主要成分潜在靶点,并利用Cytoscape3.9.0软件构建芹菜籽化合物—靶点网络图。在GeneCard数据库、OMIM数据库收集痛风相关靶点,与芹菜籽主要成分靶点取交集并导入STRING数据库进行蛋白质—蛋白质相互作用(protein-protein interaction,PPI)分析,得到核心作用靶点,将核心靶点导入DAVID数据库进行GO功能富集及KEGG通路富集。最后,应用AutoDock软件对芹菜籽关键成分与痛风靶点蛋白进行分子对接验证。结果:通过数据库收集到芹菜籽主要成分16个,对应202个活性成分靶点,经过韦恩图取与痛风交集靶点69个,经过拓扑分析表明,芹菜籽通过槲皮素、芹菜素、木犀草素、柯伊利素、芹菜甲素5种核心成分与10个痛风关键靶点TNF、MAPK14、IL4、CXCL8、LYN、PDGFRβ、HCK、VEGFA、ITGA、IL2密切关联发挥抑制或治疗痛风的作用。GO及KEGG分析结果显示,芹菜籽核心成分通过调控细胞凋亡过程、增殖、迁移等生物过程,通过PI3K-Akt信号通路、IL-17信号通路、MAPK信号通路、NF-κB信号通路等多条通路发挥作用。分子对接结果表明,5种核心成分与10个痛风疾病靶点蛋白对接结合紧密,可信度高,验证了网络药理学预测结果的准确性。结论:芹菜籽通过调控多靶点、多途径抑制或治疗痛风的作用。

Objective:To study the molecular mechanism of celery seed inhibiting or treating gout by using network pharmacology and molecular docking.Methods:TCMSP database and the network maps were constructed with Cytoscape3.9.0 software.Gout-related targets were collected in GeneCard database and OMIM database,crossed with the main component targets of celery seed and imported into STRING database for protein-protein interaction(protein-protein interaction,PPI)analysis,core targets were obtained,core targets were introduced into DAVID,and GO function enrichment and KEGG pathway enrichment were performed in the database.Finally,AutoDock software was used to verify the key components with key targets.Results:There were 16 main components of celery seeds,69 common targets.After topological analysis,quercetin,apigenin,luteolin,celery,five core components and 10 key targets of gout TNF,MAPK14,IL4,CXCL8,LYN,PDGFRβ,HCK,VEGFA,ITGA,IL2,were closely involved in inhibiting or treating gout.The results of GO and KEGG analysis showed that the core components of celery seed acted through regulating biological processes such as apoptosis,proliferation and migration,and through PI3K-Akt signaling pathway,IL-17 signaling pathway,MAPK signaling pathway,and NF-κB signaling pathway.The molecular docking results showed that the five core components were closely bound to the 10 key target proteins with high confidence,verifying the accuracy of the network pharmacology prediction results.Conclusion:This study reveals the role of celery seed in inhibiting or treating gout,and lays a foundation for the development of single Chinese herbal medicine and the study of"medicine and food homology"to control metabolic diseases.