基于网络药理学的健脾复胃颗粒防治胃癌作用机理探究

Study on Mechanism of Jianpifuwei Granules in Treatment of Gastric Cancer Based on Network Pharmacology

目的运用网络药理学探究健脾复胃颗粒在胃癌治疗中的作用机制。方法通过TCMSP数据库,根据ADME筛选出健脾复胃颗粒中君臣药成分(白术、半夏、陈皮、党参、茯苓、甘草、黄芪)及其靶点,运用Uniprot数据库,检索靶点相对应的人类基因命名;通过GeneCards、DrugBank、TTD、OMIM数据库获取胃癌主要靶点,绘制维恩图得到药物活性成分作用靶点与胃癌的主要交集靶点;Perl软件整理数据,采用Cytoscape 3.7.2软件,建立“健脾复胃颗粒中药成分-胃癌靶点”网络;利用String平台分析蛋白质间的相互作用,建立蛋白质相互作用(PPI)网络,探索网络中可能的蛋白质功能模块;采用Metascape平台进行GO富集和KEGG富集分析。结果通过TCMSP将健脾复胃颗粒君臣药经ADME筛选后共获得白术7种、半夏13种、党参21种、甘草92种、陈皮5种、茯苓15种、黄芪20种活性成分,根据Uniprot数据库,排除无对应基因名部分,排除靶点重复部分,获得靶点271个;以“gastric cancer”为检索词,搜索GeneCards数据库、OMIM数据库、DrugBank数据库以及TTD数据库中的疾病可能的作用靶点,排除重复部分,得到胃癌的潜在作用靶点6511个,利用Venny 2.1.0绘制韦恩(Venn)图,得到疾病-活性成分共同靶点213个;核心靶点有蛋白激酶B(protein kinase B,AKT1)、肿瘤抑制因子(tumor protein P53,TP53)、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素(interleukin,IL)-6、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、原癌基因JUN等。健脾复胃颗粒君臣药中关键活性成分槲皮素、柚皮素、豆甾醇、β-谷甾醇与疾病关键靶点AKT1、TP53、TNF、IL-6对接,结合能均<-5 kcal·moL^(-1),结合稳定,验证了网络药理学。结论健脾复胃颗粒在胃癌治疗中的作用机制具有多成分、多靶点、多途径的特点,为后续研究提供了思路与方法。

Objective To explore the mechanism of Jianpifuwei granules in the treatment of gastric cancer by using network pharmacology.Methods Through TCMSP database,the drug components(atractylodes macrocephala,pinellia,tangerine peel,dangshen,fuling,licorice,astragalus)and its targets were selected by ADME.GeneCards,DrugBank,TTD and OMIM databasethe main intersection target of drug active component target and gastric cancer was drawn.Perl software was used to collate the data,and Cytoscape 3.7.2 software was used to establish a network of“components of Jianpifuwei granules-gastric cancer target”.Protein interaction using String platform was analyzed,PPI network was established,and possible protein function modules in the network was explored.GO and KEGG enrichment analysis was performed.Results Through TCMSP,seven active ingredients of atractylodes macrocephala,13 pinellia ternata,21 codonopsis pilosula,92 licorice,5 tangerine peel,15 poria cocos,and 20 astragalus were obtained from the Junchen drugs of Jianpifuwei granules after screening by ADME.According to the Uniprot database,the part without corresponding gene name was excluded,and the duplicate part of target was excluded,with 271 targets.With the key word of“gastric cancer”,we searched the GeneCards database,OMIM database,DrugBank database and TTD database for possible targets of action in diseases,excluded the duplicate parts,and obtained 6511 potential targets of action in gastric cancer.Using Venny 2.1.0 to draw Venn map,we obtained 213 common targets of disease-active components;The core targets include protein kinase B(AKT1),tumor protein P53(TP53),tumor necrosis factor(TNF),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),and JUN proto-oncogene.Quercetin,naringenin,stigmasterol,andβ-sitosterol,the key active ingredients in the Junchen medicine of Jianpifuwei granules,were docked with AKT1,TP53,TNF,and IL-6,which were all<-5 kcal·moL^(-1).Combined with stability,the network pharmacology was verified.Conclusion According to the mechanism of action of Jianpifuwei granules in the treatment of gastric cancer,which has the characteristics of multi-component,multi-target and multi-channel,this paper provides ideas and methods for follow-up research.