基于网络药理学探讨白及治疗消化性溃疡的活性成分及作用机制

Exploring the active ingredients and action mechanism of Baiji in treating peptic ulcer based on network pharmacology

目的:基于网络药理学探讨白及治疗消化性溃疡的活性成分及作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)搜索白及活性成分及药物靶点信息,通过GeneCards、OMIM、DrugBank、TTD数据库查询消化性溃疡疾病的基因靶点信息。使用Perl软件、R语言、Cytoscape、STRING数据库、PMV-1.5.6软件进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,构建中药白及-活性成分-靶点-通路网络图。结果:从TCMSP数据库中筛选出9种白及活性成分,检索出223个白及靶蛋白,利用CMD分析出77个与消化性溃疡关系密切的靶蛋白。通过GeneCards、OMIM、DrugBank、TTD数据库筛选出717个消化性溃疡靶点。利用Venny 2.1软件筛选,白及治疗消化性溃疡可能通过一氧化氮合酶2(Nitric Oxide Synthase 2,NOS2)、前列腺素氧化环化酶1(Prostaglandin-Endoperoxide Synthase1,PTGS1)、雌激素受体1(Estrogen Receptor 1,ESR1)、雄激素受体(Androgen Receptor,AR)、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator Activated Receptor Gamma,PPARG)、前列腺素氧化环化酶2(Prostaglandin-Endoperoxide Synthase2,PTGS2)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、丝裂原活化蛋白激酶14(Mitogen-Activated Protein Kinase 14,MAPK14)、周期蛋白依赖激酶2(Cyclin Dependent Kinase 2,CDK2)、凝血因子Ⅶ(Coagulation FactorⅦ,F7)靶点蛋白促进炎性细胞因子渗出、减少氧化应激反应,促进溃疡愈合,从而保护消化道黏膜,达到抗溃疡的作用。结论:白及药理作用及临床应用广泛,但制剂多为中药复方或散剂,制剂较为粗糙,缺乏其药理活性成分的研究,作用机制及活性靶点尚未明确。本研究反映了白及通过多成分、多靶点、多途径治疗消化性溃疡疾病,阐述其作用机制,为新药研发以及时效性提供理论依据。

Objective:To explore the active components and action mechanism of Baiji(Bletilla striata)in treating peptic ulcer based on network pharmacology.Methods:The active ingredients of Baiji and medicine targets information were searched by TCMSP,and the gene targets information of peptic ulcer disease was searched by GeneCards,OMIM,DrugBank and TTD databases.Perl software,R language software,Cytoscape database,STRING database and PMV-1.5.6 software were used to carry out Go enrichment analysis and KEGG pathway enrichment analysis,and construct the network diagram of Baiji-active component-target-pathway.Results:9 active components of Baiji were screened from TCMSP database,223 target proteins of Baiji were retrieved,77 target proteins closely related to peptic ulcer were analyzed by CMD.717 peptic ulcer targets were screened through GeneCards,OMIM,Drugbank and TTD database.The results of Venny diagram showed that Baiji may promote inflammatory cytokine exultation,reduce oxidative stress response,promote ulcer healing,and protect the mucosa of the digestive tract through NOS2,PTGS1,ESR1,AR,PPARG,PTGS2,EGFR,MAPK14,CDK2 and F7 target proteins,thereby gaining anti-ulcer efficacy,and playing the role of treating peptic ulcer.Conclusion:The pharmacological action and clinical application of Baiji are extensive,but the preparation is mostly Chinese medicine compound or powder.The preparations are relatively rough,lack of research on its pharmacological active components,and the action mechanism and active targets are not yet clear.This study reflects that Baiji can treat peptic ulcer disease through multi-component,multi-target and multi-pathway,and expounds its action mechanism,so as to provide a theoretical basis for new medicine research and timeliness.