菊花-密蒙花药对治疗角膜损伤的作用机制

Study on the Mechanism of Chrysanthemum-Buddleja Officinalis Herb Pair in the Treatment of Corneal Injury Based on Network Pharmacology and Molecular docking

目的:基于网络药理学与分子对接探讨菊花-密蒙花药对治疗角膜损伤的作用机制。方法:选用中草药系统药理学数据库与分析平台(TCMSP)筛选出菊花-密蒙花的有效活性成分及相关作用靶点;在Genecards、OMIM、PharmGkb、DrugBank等疾病数据库检索出角膜损伤的靶点基因;再利用R软件将疾病的靶点基因与菊花-密蒙花的靶点基因进行交集分析并绘制韦恩图;运用Cytoscape构建“药物-成分-靶点”网络图;通过STRING网络平台和cytoscape软件构建蛋白质互相作用网络(PPI),并用插件CytoNCA筛选核心靶点;利用metascape平台对角膜损伤治疗关键靶点进行GO(Gene Ontology)和KEGG(KyotoEncyclo pediaof Genesand Genomes)富集分析。通过PyMOL和Auto DockVina等软件,将菊花-密蒙花药对的活性成分和核心靶点进行分子对接,并根据其结合能判断亲和力大小。结果:共收集17个有效成分及586个药物靶点;角膜损伤疾病靶点2797个;药物成分和疾病的共有靶点146个;最终得到14个核心靶点:JUN、TP53、MYC、MAPK14、MAPK3、RELA、MAPK1、ESR1、FOS、NFKBIA、AKT1、RB1、CCND1、CDKN1A。GO功能富集分析得到共1949条,其中生物过程主要与无机物的反应、激素的反应、细胞因子的反应、细胞对脂质的反应及细胞对氮化合物的反应等相关。KEGG富集分析结果显示,作用机制主要涉及糖尿病并发症中的AGE-RAGE信号通路、PI3K-Akt信号通路、IL-17信号通路、TNF信号通路、细胞衰老等信号通路。分子对接显示木犀草素及槲皮素与4个关键靶点均<-5.0,表明核心活性成分和关键靶点蛋白均有较好的结合能力,该药对可能通过以上靶点作用于角膜损伤的治疗。结论:菊花-密蒙花药对可能通过涉及糖尿病并发症中的AGE-RAGE信号通路、PI3K-Akt信号通路、IL-17信号通路、TNF信号通路、细胞衰老等信号通路参与调节炎症反应及细胞的增殖、分化与凋亡,从而起到防治角膜损伤的作用,这为后续角膜损伤治疗的深入探讨提供一定的参考。

Objective:Based on network pharmacology and molecular docking,to explore the mechanism of action of chrysanthemum-Buddha anthers on corneal injury.Methods:The Chinese Herbal Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to screen out the active ingredients and related targets of Chry-santhemum-Buddha Budisma;the target genes of corneal damage were retrieved from Genecards,OMIM,PharmGkb,DrugBank and other disease databases;and then use R software to conduct intersection analysis of disease target genes and chrysanthemum-buddleia target genes and draw a Venn diagram;use Cytoscape to build a“drug-ingredient-target”network diagram;through the STRING network platform and cytoscape The software constructs the protein interaction network(PPI),and uses the plug-in CytoNCA to screen the core targets;uses the metascape platform to perform GO(Gene Ontology)and KEGG(KyotoEncyclo pediaof Genesand Genomes)enrichment analysis on the key targets of corneal injury treatment.Through PyMOL and Auto DockVina and other software,the active components of the chrysanthemum-Buddha anther pair and the core target were molecularly docked,and the affinity was judged according to their binding energy.Results:A total of 17 active ingredients and 586 drug targets were collected;2797 corneal injury disease targets;146 common targets of drug ingredients and diseases;finally 14 core targets were obtained:JUN,TP53,MYC,MAPK14,MAPK3,RELA,MAPK1,ESR1,FOS,NFKBIA,AKT1,RB1,CCND1,CDKN1A.GO functional enrichment analysis obtained a total of 1949 items,among which biological processes were mainly related to the response of inorganic substances,hormones,cytokines,cells to lipids,and cells to nitrogen compounds.The results of KEGG enrichment analysis showed that the mechanism of action mainly involves AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,IL-17 signaling pathway,TNF signaling pathway,cell senescence and other signaling pathways in diabetic complications.Molecular docking showed that luteolin and quercetin were all<-5.0 with the four key targets,indicating that the core active ingredients and key target proteins have good binding ability,and the drug pair may act on corneal damage through the above targets Treatment.Conclusion:The chrysanthemum-Buddha anther pair may be involved in the regulation of inflammatory response and cell growth through the AGE-RAGE signaling pathway,PI3KAkt signaling pathway,IL-17 signaling pathway,TNF signaling pathway,cell senescence and other signaling pathways involved in diabetic complications.Proliferation,differentiation and apoptosis,so as to prevent and treat corneal injury,which provides a certain reference for the subsequent in-depth discussion of corneal injury treatment.