基于网络药理学和分子对接探讨班氏促卵助孕汤治疗卵巢储备功能低下的研究

Study on the Mechanism of Treating Diminished Ovarian Reserve with Ban’s Culuan Zhuyun Tang Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接探讨班氏促卵助孕汤对卵巢储备功能低下的影响。方法:通过中药系统药理学(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中药分子机制分析中药综合数据库(traditional Chinese medicine integrative database for herb molecular mechanism analysis,TCMID)、借助中药分子机理的生物信息学分析工具(bioinformatics analysis tool for molecular mechanism of traditional chinese medicine,BATMAN-TCM)检索班氏促卵助孕汤的活性成分以及作用靶点;通过GeneCards、OMIM数据库获取卵巢储备功能低下的相关靶标。由Cytoscape软件和STRING数据库建立药物-化合物-靶标网络、靶标蛋白互作PPI网络。R语言的cluster Profiler工具包对于核心靶点展开基因本体(gene ontology,GO)功能富集以及基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。最后,对药物活性成分与疾病靶点进行分子对接验证。结果:根据筛选条件得到245个化合物和250个药物相应靶点。PPI核心网络包含80个蛋白,关键蛋白涉及INS、IL6、APP、VEGFA、EGFR、MAPK8等。GO功能富集分析取得1296个条目(P<0.05),其中生物过程(biological process,BP)1094个,细胞组成(cell composition,CC)88个,分子功能(molecular function,MF)114个;KEGG通路富集有63条通路与卵巢储备功能低下相关(P<0.05),涉及cAMP信号通路、HIF-1信号通路、雌激素信号通路、催乳激素信号通路等。分子对接结果表明,班氏排卵促孕汤的主要活性成分槲皮素、山柰酚、β-谷甾醇与核心靶点INS、IL6、APP具有较好的结合活性。结论:班氏促卵助孕汤中的活性化合物可通过多靶点、多通路治疗卵巢储备功能低下。

Objective:To explore the effects of Ban′s Culuan Zhuyun Tang on diminished ovarian reserve(DOR)based on network pharmacology and molecular docking.Methods:The active ingredients and targets of Ban′s Culuan Zhuyun Tang were searched via TCMSP,TCMID and BATMAN-TCM;the related targets of DOR were obtained by GeneCards and OMIM databases.Drug-compound-target networks,and target protein interaction PPI network were established via Cytoscape software and STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of the core targets were performed by using cluster Profiler tool kit of R language.Finally,active ingredients of the drug was validated by molecular docking with the disease target.Results:According to the screening conditions,245 compounds and 250 corresponding targets of the drugs were obtained.PPI core network contained 80 proteins,and key proteins involved INS,IL6,APP,VEGFA,EGFR,MAPK8 and others.GO functional enrichment analysis yielded 1296 entries(P<0.05),among them,1094 BP,88 CC and 114 MF;KEGG pathway enrichment found 63 pathways related to DOR(P<0.05),involving cAMP signaling pathway,HIF-1 signaling pathway,estrogen signaling pathway and prolactin signaling pathway.The results of molecular docking presented that the main active ingredients in Ban′s Culuan Zhuyun Tang were quercetin,kaempferol,β-sitosterol,which showed good binding activity with core targets INS,IL6 and APP.Conclusion:The active ingredients in Ban′s Culuan Zhuyun Tang could treat DOR through multiple targets and pathways.