基于网络药理学和分子对接分析姚乃礼教授健脾祛湿解毒通络方治疗幽门螺杆菌感染的机制

Mechanism of Jianpi Qushi Jiedu Tongluo Decoction Applied by Professor YAO Naili in Treatment of Helicobacter Pylori Infection Based on Network Pharmacology and Molecular Docking

[目的]基于网络药理学和分子对接方法,挖掘姚乃礼教授健脾祛湿解毒通络方治疗幽门螺杆菌(Helicobacter pylori,Hp)感染的作用机制。[方法]应用中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP),检索并获取健脾祛湿解毒通络方药物的活性成分及靶点,通过人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)、人类基因综合数据库(Human Gene Comprehensive Database,GeneCards)和DrugBank数据库获取Hp感染相关靶点,对药物靶点与疾病靶点取交集,作为健脾祛湿解毒通络方治疗Hp感染的潜在作用靶点。采用Cytoscape 3.7.0软件构建药物-成分-共有靶点网络,通过STRING网站构建蛋白互作(protein protein interaction,PPI)网络,通过Metascape平台进行基因本体(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。利用AutoDock软件,对核心靶点和度值前5位的主要活性成分进行分子对接。[结果]健脾祛湿解毒通络方治疗Hp感染有126个靶点,涉及118个活性成分,Cytoscape 3.7.0软件筛选出槲皮素、β-谷甾醇、金合欢素、山柰酚、豆甾醇等主要活性成分,PPI网络分析后得到肿瘤蛋白P53(tumor protein p53,TP53)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、转录因子p65(transcription factor p65,RELA)、丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、酪氨酸蛋白激酶B1(threonine protein kinase B1,AKT1)、MAPK1、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)等核心靶点,参与对脂多糖的反应、对外来刺激的反应等生物过程,涉及癌症相关通路、叉头框转录因子O(forkhead box protein O,FOXO)、缺氧诱导因子-1(hypoxia induced factor-1,HIF-1)、核因子-κB(nuclear factor-κB,NF-κB)信号通路等多条通路。分子对接结果表明,健脾祛湿解毒通络方主要活性成分与核心靶点结合能力较强,验证了上述预测结果。[结论]健脾祛湿解毒通络方中多种成分可作用于Hp感染相关靶点,通过多条通路发挥作用,为深入研究健脾祛湿解毒通络方治疗Hp感染提供了参考。

[Objective]To explore the mechanism of Jianpi Qushi Jiedu Tongluo Decoction applied by Professor YAO Naili in treatment of Helicobacter pylori(Hp)infection by network pharmacology and molecular docking.[Methods]The active components and targets of Jianpi Qushi Jiedu Tongluo Decoction were retrieved and obtained by the Traditional Chinese Medicine Systems Pharmacology(TCMSP),Gene targets related to Hp were acquired through Online Mendelian Inheritance in Man(OMIM),Human Gene Comprehensive Database(GeneCards)and DrugBank database.To acquire the intersection of drug targets and disease targets as the potential targets of Jianpi Qushi Jiedu Tongluo Decoction in the treatment of Hp infection,the cytoscape 3.7.0 software was used for construction of drug-componentcommon target network,the STRING website was used to build protein protein interaction(PPI)network,the Metascape platform was used for gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.AutoDock software was used to perform molecular docking between the core targets and the main active components in the top five degrees.[Results]Jianpi Qushi Jiedu Tongluo Decoction has 126 targets in the treatment of Hp infection,involving 118 active ingredients,the main active ingredients were screened such as quercetin,beta-sitosterol,Acacetin,kaempferol and stigmasterol by cytoscape 3.7.0,the core targets such as tumor protein P53(TP53),signal transducer and activator of transcription 3(STAT3),transcription factor p65(RELA),mitogen activated protein kinase 3(MAPK3),threonine protein kinase 1(AKT1),MAPK1,tumor necrosis factor(TNF)and interleukin-6(IL-6)were obtained from PPI network analysis.It involved biological processes such as response to lipopolysaccharide and xenobiotic stimulus,and pathways such as cancer related pathway,forkhead box protein O(FOXO),hypoxia induced factor-1(HIF-1),nuclear factor-κB(NF-κB)signaling pathway.Molecular docking showed that the main active components of Jianpi Qushi Jiedu Tongluo Decoction had strong binding ability to core targets,which verified the above prediction results.[Conclusion]Various components of Jianpi Qushi Jiedu Tongluo Decoction have effects on Hp infection related targets through multiple pathways,providing reference for further research on Jianpi Qushi Jiedu Tongluo Decoction in the treatment of Hp infection.