基于网络药理学探讨鹅不食草治疗鼻咽癌的作用机制

Mechanism of action of Centipeda minima in treatment of nasopharyngeal carcinoma:A study based on network pharmacology

目的:应用网络药理学与分子对接技术探讨鹅不食草治疗鼻咽癌(NPC)的作用机制。方法:从TCMSP、Batman-TCM、ETCM数据库获取鹅不食草的活性成分和作用靶点;利用OMIM、GeneCards、TTD、Pharmgkb数据库筛选NPC相关靶点;使用Venny 2.0.1平台筛选药物与疾病作用的交集靶点;采用Cytoscape 3.8.0软件构建“药物-成分-靶点-疾病”网络;利用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络;将所获得的交集靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析;使用AutoDock Vina对鹅不食草的核心活性成分及NPC的关键靶点进行分子对接。结果:获得鹅不食草化学成分17种,相关靶点420个,NPC疾病相关靶点共2332个,鹅不食草-NPC交集靶点140个。鹅不食草主要活性成分包括槲皮素、豆甾醇、谷甾醇等。治疗NPC的关键靶点包括蛋白激酶B1(AKT1)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)等,主要涉及凋亡等生物过程及癌症、炎症、凋亡等信号通路。分子对接结果验证了主要活性成分及核心靶点均具有较好的结合能力。结论:鹅不食草通过多成分-多靶点-多通路治疗NPC,本研究为进一步深入研究其治疗NPC的作用机制奠定了的基础。

Objective:To investigate the mechanism of action of Centipeda minima in the treatment of nasopharyngeal carcinoma(NPC)based on network pharmacology and molecular docking.Methods:TCMSP,BatmanTCM,and ETCM databases were used to obtain the active components and action targets of Centipeda minima,and OMIM,GeneCards,TTD and Pharmgkb databases were used to obtain the targets associated with NPC.Venny 2.0.1 platform was used to obtain the intersecting targets of the drug and the disease,and Cytoscape 3.8.0 was used to construct a drug-component-target-disease network.STRING database was used to construct a protein-protein interaction(PPI)network,and gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for the intersecting targets obtained.AutoDock Vina was used to perform molecular docking between the core active components of Centipeda minima and the key targets of NPC.Results:A total of 17 chemical components and 420 related targets were obtained for Centipeda minima,and 2332 targets were obtained for NPC,with 140 intersecting targets between Centipeda minima and NPC.The main active components of Centipeda minima included quercetin,stigmasterol,and sitosterol.The key targets in the treatment of NPC included protein kinase B1(AkT1),tumor necrosis factor(TNF),and interleukin-6(IL-6),mainly involving the biological process of apoptosis and the signaling pathways of cancer,inflammation,and apoptosis.Molecular docking showed good binding capacity between the main active components and the core targets.Conclusion:Centipeda minima exerts a therapeutic effect on NPC through multiple components,targets,and pathways,and this study lays a foundation for further research on the mechanism of action of Centipeda minima in the treatment of NPC.