基于网络药理学和分子对接探讨丹参-郁金治疗多囊卵巢综合征的作用机制

Mechanism of Radix Salviae Miltiorrhizae-radix Curcumae in the Treatment of Polycystic Ovary Syndrome Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学和分子对接探究丹参-郁金治疗多囊卵巢综合征(PCOS)的作用机制。方法:获取丹参、郁金的中药活性成分及其作用靶点,检索PCOS疾病相关靶点,将二者取交集后利用Cytoscape 3.7.2构建“药物-成分-共同靶点”网络。并将共同靶点导入string数据库构建蛋白质-蛋白质相互作用(PPI)网络图。再将共同靶点基因导入DAVID数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。最后根据活性成分、作用靶点的相关节点参数进行排序,使用AutoDock Tools将核心活性成分和筛选出的靶基因编码的蛋白进行分子对接。结果:丹参、郁金共筛选出潜在活性成分80个,其中木犀草素、丹参酮Ⅱa、β谷甾醇等19种为主要活性成分,活性成分的作用靶点共157个。PCOS疾病相关靶点1847个,交集靶点为93个,PPI网络及拓扑学分析显示AKT1、TP53、IL6、VEGFA、MAPK3、MAPK1是丹参、郁金治疗PCOS的核心靶点。GO功能富集分析显示丹参-郁金主要参与RNA信号转导、酶的调控等生物过程,KEGG通路富集分析得到了癌症信号通路、PI3K/AKT、FoxO、HIF-1等20条相关性最高的通路。将核心靶点编码的蛋白作为靶点分别与对应的药物核心活性成分对接,结果良好。结论:通过网络药理学研究及分子对接验证,显示丹参-郁金可通过多靶点、多信号通路对PCOS的疾病发生及进展起到一定的治疗、干预作用。

Objective:To explore the mechanism of Radix Salviae Miltiorrhizae-Radix Curcumae in the treatment of polycystic ovary syndrome(PCOS)based on network pharmacology and molecular docking.Methods:The active components of Radix Salviae Miltiorrhizae and Radix Curcumae and their targets were obtained,and PCOS-related targets were searched.The targets of active components of Radix Salviae Miltiorrhizae-Radix Curcumae and the PCOS-related targets were intersected,and Cytoscape 3.7.2 was used to construct the drug-component-common target network.The common targets were imported into String to construct protein-protein interaction(PPI)network diagram.Then Gene Ontology(GO)and Kyoto Gene and Genome Encyclopedia(KEGG)enrichment analyses were performed on the genes of the common targets in DAVID.Finally,according to the relevant node parameters of active components and targets,AutoDock Tools was used to dock the core active components with the proteins encoded by the screened target genes.Results:A total of 80 potential active components were screened out,among which 19,including luteolin,tanshinone ⅡA,and β-sitosterol,were considered as the key active components,and 157 targets of the drug pair were found.There were 1847 PCOS-related targets,and 93 intersected targets.The PPI network and topological analysis indicated that serine/threonine kinase 1(AKT1),tumor protein P53(TP53),interleukin 6(IL6),vascular endothelial growth factor A(VEGFA),mitogen-activated protein kinase 3(MAPK3)and MAPK1 were the core targets of Radix Salviae Miltiorrhizae-Radix Curcumae in the treatment of PCOS.GO enrichment analysis showed that Radix Salviae Miltiorrhizae-Radix Curcumae was mainly involved in RNA signal transcription,enzyme regulation and other biological processes.The 20 pathways with highest correlation were obtained from KEGG pathway enrichment analysis,including cancer,phosphatidylinositol-3-kinase/Akt(PI3 K/Akt),forkhead box O(FoxO),and hypoxia inducible factor-1(HIF-1)signaling pathways.The molecular docking revealed good results.Conclusion:Through network pharmacology and molecular docking verification,it was found that Radix Salviae Miltiorrhizae-Radix Curcumae played a certain therapeutic intervention role in the occurrence and progress of PCOS via multi-targets and multi-signaling pathways.