基于网络药理学和分子对接研究广藿香治疗胃癌的作用机制★

Mechanism of Pogostemon cablin in treatment of gastric cancer based on network pharmacology and molecular docking★

摘要:

目的 基于网络药理学和分子对接技术探讨广藿香治疗胃癌的活性成分及潜在的作用机制。方法 经TCMSP平台筛选和文献挖掘收集广藿香的主要活性成分，通过GeneCards数据库筛选出胃癌的靶点，利用R语言编程将化合物作用靶点与疾病靶点映射，构建化合物-靶点网络图。应用String数据库、R语言编程结合Cytoscape 软件构建胃癌靶点蛋白相互作用网络并进行分析。应用Metascape网站进行基因本体论（GO）功能富集和京都基因与基因组百科全书（KEGG）通路富集分析。应用DS软件对广藿香活性成分与胃癌靶点进行分子对接验证。结果 广藿香中含有7个主要活性成分，对应胃癌的143个靶点，主要通过AKT1、IL-6、EGFR、MMP9、VEGFA、CASP3、MARK1等关键靶点发挥疗效，主要作用途径为癌症途径、IL-17信号通路、铂耐药、NF-κB信号通路、癌症中的转录失调、血管内皮生长因子信号通路等。至少有5个活性成分可与核心靶点AKT1相互作用，其中槲皮素7-O-β-D-葡萄糖苷与AKT1的结合最为稳定。结论 广藿香治疗胃癌具有多靶点和多通路的潜在作用机制。

Abstract:

Objective To study the active components and potetial mechanism of Pogostemon cablin in the treatment of gastric cancer based on network pharmacology and molecular docking.Methods The main active components of Pogostemon cablin were collected through TCMSP platform screening and literature mining. The targets of gastric cancer were screened through GeneCards database. The active components were mapped to the disease targets by R programming language, and the interaction network of gastric cancer targeting proteins was constructed and analyzed by String database, R programming language and Cytoscape software. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) enrichment were conducted on Metascape website. The molecular docking between the active components of Pogostemon cablin and gastric cancer targets was verified by DS software.Results There were 7 active components in Pogostemon cablin, corresponding to 143 targets of gastric cancer. They acted mainly through AKT1, IL-6, EGFR, MMP9, VEGFA, CASP3, MARK1 and other key targets, via pathways in cancer, IL-17 signaling pathway, platinum resistance, NF-κB signaling pathway, transcription disorders in cancer, vascular endothelial growth factor signaling pathway, etc. At least five active components could be successfully docked with the core target AKT1, and the quercetin 7-O-β-D-glucoside could be bound to AKT1 the most stably.Conclusion Pogostemon cablin could inhibit the gastric cancer through multi-compound, multi-target, and multi-pathway.