基于网络药理学和分子对接分析豆根管食通口服液治疗食管癌的分子机制  

Molecular Mechanism of Dou Gen Guan Shi Tong Oral Liquid in Treatment of Esophageal Cancer Based on Network Pharmacology and Molecular Docking

作　　者：邝玉慧 陈欣菊[2] 徐方飚 陈晓琦[2] 郑玉玲[2] KUANG Yuhui;CHEN Xinju;XU Fangbiao;CHEN Xiaoqi;ZHENG Yuling(Henan University of Chinese Medicine,Zhengzhou Henan China 450046;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou Henan China 450000)

机构地区：[1]河南中医药大学,河南郑州450046 [2]河南中医药大学第一附属医院,河南郑州450000

出　　处：《中医学报》2022年第2期383-390,共8页Acta Chinese Medicine

基　　金：国家自然科学基金青年项目(81804063);中国博士后科学基金面上项目(2019M662500);河南省中医药研究专项课题项目(2018ZY2032)。

摘　　要：目的:通过网络药理学和分子对接技术分析豆根管食通口服液治疗食管癌的分子机制。方法:检索多个数据库并筛选豆根管食通口服液有效活性成分和其作用于食管癌(esophageal carcinoma,EC)的相关靶点,并采用Cytoscape软件分别构建"药物-活性成分-靶点""靶点-通路"网络图;采用CytoHubba插件中多种算法筛选豆根管食通口服液治疗EC关键靶点,并采用R软件对关键靶点进行基因本体(gene discovery,GO)生物功能富集分析和京都基因与基因组百科全书(kyoto encyclopodia of genes and genomes,KEGG)信号通路富集分析;采用分子对接技术对有效活性化合物和靶蛋白的结合能力进行验证。结果:从豆根管食通口服液方中药中共筛选出59种活性成分,治疗EC靶点106个,其中关键靶点21个。KEGG信号通路富集分析发现,关键靶点主要富集在白细胞介素-17(interleukin 17,IL-17)信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路等107个通路;GO生物功能富集分析发现,关键靶点主要涉及DNA结合转录因子活性的调节、细胞对氧化应激的反应等1341个生物过程,丝裂原活化蛋白激酶(mitogen activated protein kinases,MAPK)活性、生长因子活性等59个分子功能,细胞定位在囊泡腔、膜区等26个细胞组分。分子对接提示药物活性成分β-谷甾醇、山柰酚、槲皮素与表皮生长因子受体和MAPK3靶点对接良好。结论:豆根管食通口服液治疗EC具有多成分、多途径、多靶点的优势。Objective:Analyze the molecular mechanism of Dou Gen Guan Shi Tong Oral Liquid in treatment of esophageal cancer through network pharmacology and molecular docking technology.Methods:Search through multiple databases and screen the effective active ingredients of Dou Gen Guan Shi Tong Oral Liquid and its related targets for esophageal carcinoma(EC),and use Cytoscape software to construct"drug-active ingredient-target"and"target-pathway"network diagrams.Using multiple algorithms in the Cyto Hubba plug-in to screen the key targets of Dougenguan Shitong Oral Liquid for the treatment of EC.And use R software to conduct gene ontology(GO)biological function enrichment analysis and Kyoto encyclopodia of genes and genomes(KEGG)pathway enrichment analysis for key targets.Furthermore,molecular docking technology is used to verify the binding ability of the effective active compound and the target protein.GO biological positive energy enrichment analysis found that the key targets mainly involved 1341 significant biological processes such as the regulation of DNA binding transcription factor activity and cell response to oxidative stress,59 significant molecular functions such as MAP kinase activity and growth factor activity,and 26 significant differences in vesicle cavity and membrane region.Molecular docking suggested that the active components ofβ-sitosterol,kaempferol,and quercetin docked well with EGFR and MAPK3 targets.Conclusion:Dou Gen Guan Shi Tong Oral Liquid has the advantages of multiple components,multiple pathways,and multiple targets in the treatment of EC.

关 键 词：豆根管食通口服液 食管癌 网络药理学 分子对接 作用机制 

分 类 号：R285.6[医药卫生—中药学]