基于网络药理学探索扶正抑瘤汤治疗胶质瘤的作用机制

Network Pharmacology Analysis of the Anti-Glioma Pharmacological Mechanisms of Fuzheng Yiliu Decoction

摘要: 目的：探索扶正抑瘤汤治疗胶质瘤的关键有效成分和作用机制。方法：基于网络药理学方法利用TCMSP、DisGeNET、GeneCards等数据库收集相关靶基因；分别通过Venny平台、String数据库、DAVID数据库、KEGG数据库分析数据，获得扶正抑瘤汤治疗胶质瘤的交集基因、蛋白互作图，GO分析结果和KEGG通路；最后使用GraphPad Prism8和Cytoscape3.8.2软件CytoHubba插件绘图实现数据可视化。结果：本次研究发现方剂治疗胶质瘤的关键有效成分为红芪所含槲皮素、柚皮素、芒柄花黄素，方剂治疗胶质瘤关键靶基因分别是肿瘤抑制蛋白质p53 (p53)、原癌基因蛋白质c-akt (AKT1)、N-Myc原癌基因蛋白质(MYC)、丝裂原活化蛋白激酶1 (MAPK1)、血管内皮生长因子A (VEGFA)，主要通过PI3K/Akt通路、Ras-Raf-MAPK通路、p53通路、VEGF通路等多条通路发挥功效。结论：扶正抑瘤汤以红芪为方剂之首，四组分合理配伍；以黄酮类化合物为有效成分之首，多成分协同增效；通过AKT1、MAPK、p53、VEGF、MYC等多条靶基因相关通路综合发挥胶质瘤治疗作用。

Abstract: Objective: To clarify the mechanism of Fuzheng Yiliu Decoction in the treatment of glioma and ex-plore the key effective components and key target genes. Methods: Collected the target genes re-lated to Fuzheng Yiliu Decoction and glioma based on the network pharmacology methods; Ob-tained the protein-protein interaction network, gene ontology analysis results and metabolic path-ways by analyzing prescription and disease intersection genes; Used Cytoscape3.8.2 and GraphPad Prism8 softwares to realize data visualization. Results: It was found that quercetin, naringin and formononetin contained in Hongqi of Fuzheng Yiliu Decoction were the key active components in the treatment of glioma. The key target genes of glioma treated by prescription are Tumor Suppressor Protein p53 (p53), Proto-Oncogene Proteins c-akt (Akt1), N-Myc Proto-Oncogene Protein (Myc), Mi-togen-Activated Protein Kinase 1 (MAPK1), Vascular Endothelial Growth Factor A (VEGFA), respec-tively. Prescription exerted effects mainly through PI3K/Akt pathway, Ras-RAF-MAPK pathway, p53 pathway, VEGF pathway etc. Conclusion: Four components of Fuzheng Yiliu Decoction are rea-sonably compatible which Hongqi is the most important. Flavones as the most effective components play synergistic effect with multiple components. Fuzheng Yiliu Decoction comprehensively through multiple target gene-related pathways such as Akt1, MAPK, p53, VEGF and MYC treats glioma.