基于网络药理学和分子对接探讨大补元煎治疗早发性卵巢功能不全的作用机制

Mechanism of Dabuyuan Decoction in Treatment of Premature Ovarian Insufficiency based on Network Pharmacology and Molecular Docking

目的通过网络药理学和分子对接的方法初步探讨大补元煎治疗早发性卵巢功能不全(POI)的作用机制。方法在TCMSP数据库中检索大补元煎8味中药名得出其活性成分及靶点的相关信息,检索GeneCards和OMIM数据库,得到POI疾病靶点的相关信息,筛选出大补元煎与POI的共同基因靶点信息,利用Cytoscape软件构建大补元煎治疗POI的活性成分-靶点网络图。利用STRING数据库进行共同基因靶点信息的蛋白质互作(PPI)网络构建;利用Metascape数据库对共同基因靶点进行生物信息学分析,包括基因本体(GO)功能富集和京都基因和基因组百科全书(KEGG)通路富集相关分析。应用AutoDock和Py Mol软件进行活性成分及关键靶点之间的分子对接验证。结果将获得的8味中药共176个活性成分和282个靶点与POI的1284个疾病靶点取交集,得到71个交集靶点。进行PPI分析得到核心靶点基因:蛋白激酶B(Akt)1、白细胞介素-6、血管内皮生长因子A、肿瘤蛋白53、雌激素受体1等,通过GO功能和KEGG通路富集分析显示,核心靶点基因的GO分析主要参与生物过程,主要富集在癌症、磷脂酰肌醇-3-激酶/Akt、促分裂原活化的蛋白激酶、Janus激酶-信号转导及转录活化因子、叉头框转录因子O、卵巢类固醇激素生成等信号通路。分子对接结果显示,肿瘤坏死因子(TNF)-豆甾醇、TNF-山柰酚、TNF-刺芒柄花素、TNF-槲皮素、TNF-β-谷甾醇、Akt1-刺芒柄花素等均具有较高的结合性。结论大补元煎可能通过多种有效成分作用于共同核心靶点影响卵巢功能、炎性衰老、葡萄糖代谢等,发挥治疗POI的作用。

Objective To preliminarily explore the mechanism of Dabuyuan decoction in the treatment of premature ovarian insufficiency(POI)through the method of network pharmacology and molecular docking.Methods The active ingredients and target information of 8 traditional Chinese herbal medicines were retrieved in the TCMSP database,the GeneCards and OMIM databases were searched to obtain the relevant information of POI disease targets and screen out the common gene target information of Dabuyuan decoction and POI,and Cytoscape software was used to construct the active ingredient target network diagram of Dabuyuan decoction for treating POI.A protein-protein interaction(PPI)network with common gene target information was constructed using the STRING database;the Metascape database was used for bioinformatics analysis of common gene targets,including gene ontology(GO)function enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment correlation analysis.AutoDock and PyMol software were used to verify the molecular docking between active ingredients and key targets.Results A total of 176 active ingredients and 282 targets from the 8 Chinese herbal medicines obtained were intersected with 1284 disease targets of POI,resulting in 71 intersected targets.Through PPI analysis,core target genes were obtained:protein kinase B(Akt)1,interleukin-6,vascular endothelial growth factor A,tumor protein 53,estrogen receptor 1,etc.Through GO function and KEGG pathway enrichment analysis,it was found that GO analysis of core target genes was mainly involved in the biological process,mainly enriched in signal pathways such as cancer,phosphatidylinositol-3-kinase/Akt,mitogen activated protein kinase,Janus kinase signal transduction and transcription activation factors,forkhead box transcription factor O and ovarian steroid hormone production.The results of molecular docking showed that tumor necrosis factor(TNF)-stigmasterol,TNF-kaempferol,TNF-formononetin,TNF-quercetin,TNF-β-glutosterol,Akt1-formononetin,etc.all have high binding capacity.Conclusion Dabuyuan decoction may affect ovarian function,inflammatory aging,glucose metabolism,etc.through a variety of active ingredient acting on common core targets,and play a role in treating POI.