基于网络药理学和分子对接技术探讨儿脾醒颗粒治疗小儿厌食症的作用机制  

Mechanism of Erpixing Granules in treatment of infantile anorexia based on network pharmacology and molecular docking technology

作　　者：董亚闻 郭圣璇 蔡秋晗 DONG Ya-wen;GUO Sheng-xuan;CAI Qiu-han(Tianjin Children’s Hospital,Tianjin University Children's Hospital,Tianjin 300134,China;Clinical Trials Centre,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300193,China)

机构地区：[1]天津市儿童医院天津大学儿童医院,天津300134 [2]天津中医药大学第一附属医院临床试验中心,天津300193 [3]国家中医针灸临床医学研究中心,天津300193

出　　处：《现代药物与临床》2023年第2期308-316,共9页Drugs & Clinic

摘　　要：目的采用网络药理学和分子对接技术探讨儿脾醒颗粒治疗小儿厌食症的潜在作用机制。方法通过检索中药系统药理学数据库与分析平台(TCMSP)数据库获取儿脾醒颗粒的主要活性成分及对应靶点;检索GeneCards、OMIM、DrugBank、TTD数据库得到小儿厌食症相关靶点基因;取药物靶点与疾病靶点的交集,得出儿脾醒颗粒治疗小儿厌食症的有效靶点并绘制Venn图;运用Cytoscape 3.9.0软件构建药物与小儿厌食症疾病靶点互作网络图;利用STRING数据库绘制蛋白质相互作用(PPI)的可视化网络图,并进行网络拓扑分析;通过Bioconductor数据库和R语言对交集靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,了解儿脾醒颗粒治疗小儿厌食症可能的生物过程及通路;最后运用SYBYL-x2.0软件实现分子对接验证。结果获得儿脾醒颗粒主要活性成分46个、药物靶点蛋白236个;检索小儿厌食症疾病相关靶点共1372个,活性成分与疾病交集靶点118个;发现儿脾醒颗粒通过作用于转录因子AP-1(JUN)、V-Rel网状内皮增生病毒癌基因同源物A(RELA)、肿瘤坏死因子(TNF)、白细胞介素(IL)、磷脂酰肌醇3-激酶/蛋白激酶(PI3K/Akt)等13个关键靶点发挥着治疗小儿厌食症的药理作用;GO和KEGG富集分析结果显示,潜在作用靶点涉及2521条生物学功能、181条信号通路;分子对接结果显示儿脾醒颗粒有效成分与多个疾病靶点蛋白具有较高结合力。结论儿脾醒颗粒可能通过调节JUN、RELA、TNF、IL、PI3K/Akt等关键靶点发挥多成分–多靶点–多通路作用机制,为进一步的机制研究及临床广泛应用提供参考。Objective To explore the potential mechanism of Erpixing Granules in treatment of infantile infantile anorexia by using network pharmacology and molecular docking.Methods The active components and corresponding targets in Erpixing Granules were retrieved from the TCMSP database.Infantile anorexia related target genes were obtained by searching GeneCards,OMIM,DrugBank,and TTD databases.The drug target and the disease target were intersected to obtain the effective targets of Erpixing Granules in treatment of infantile anorexia,and the drug disease Venn diagram was drawn.Cytoscape 3.9.0 software was used to construct a network diagram of drug-disease target interaction.The protein-protein interaction(PPI)network was constructed by using STRING database,and the network topology was analyzed.Through Bioconductor database and R language,GO and KEGG enrichment analysis of relevant targets were conducted to understand the possible biological processes and pathways of Erpixing Granules in reatment of infantile anorexia.Finally,molecular docking verification is carried out by using SYBYL-x2.0 software.Results 46 Active components and 236 drug targets of Epixing Granules were screened.A total of 1372 targets related to anorexia were retrieved,and 118 targets were common between active ingredients and diseases.13 Key targets such as JUN,RELA,TNF,IL,and PI3K-Akt were found to play an important role in treatment of infantile anorexia with Erpixing Granules.GO and KEGG enrichment analysis showed that 2521 biological functions and 181 signaling pathways were involved in the potential targets.The results of molecular docking showed that the active compounds of Erpixing Granules had high binding ability to several key disease targets.Conclusion Erpixing Granules may play a multi-component,multi-target and multi-pathway mechanism by regulating JUN,RELA,TNF,IL,PI3K-Akt and other key targets,which provides reference for further mechanism research and clinical application.

关 键 词：儿脾醒颗粒 小儿厌食症 网络药理学 分子对接 槲皮素 山柰酚 转录因子AP-1 V-Rel网状内皮增生病毒癌基因同源物A 

分 类 号：R985[医药卫生—药品]