基于网络药理学和分子对接研究加减蠲痰方治疗多囊卵巢综合征的作用机制

Mechanism of action of modified Juantan Prescription in treatment of polycystic ovary syndrome:A study based on network pharmacology and molecular docking

目的:基于网络药理学和分子对接研究加减蠲痰方治疗多囊卵巢综合征(PCOS)的作用机制。方法:通过TCMSP数据库获取加减蠲痰方的药物有效成分及作用靶点;利用GeneCards、OMIM等数据库筛选PCOS相关靶点;通过微生信平台获得加减蠲痰方与PCOS的交集靶点。利用Cytoscape 3.7.1软件构建药物、靶点与疾病之间的关系网络。应用STRING数据库构建交集靶点的蛋白质-蛋白质相互作用(PPI)网络,并运用Metascape数据库进行基因本体(GO)功能、京都基因与基因组百科全书(KEGG)通路富集分析。利用分子对接技术验证关键成分与核心靶点的对接能力。结果:获得山柰酚、豆甾醇、异鼠李素、汉黄芩、柚皮素等96种活性成分,有丝分裂激活蛋白激酶3(MAPK3)、细胞肿瘤抗原p53(TP53)、有丝分裂激活蛋白激酶1(MAPK1)、转录因子AP-1、蛋白激酶B1等126个交集靶点以及磷脂酰肌醇3-激酶/蛋白激酶B、丝裂原激活的蛋白激酶、肿瘤坏死因子、转录因子、糖尿病并发症中的晚期糖基化终产物及其受体(AGE-RAGE)信号通路。槲皮素与9个关键靶点均可良好结合,结果排前3位的靶点为MAPK3、TP53、MAPK1。结论:加减蠲痰方治疗PCOS具有多成分、多靶点、多通路的特点,可能通过改善胰岛素抵抗、抑制颗粒细胞自噬并促进卵泡发育、减轻排卵障碍、促进细胞凋亡、调控血糖稳态、调节激素水平、抗炎等药理作用来调治PCOS,为后期进一步研究提供理论依据。

Objective:To investigate the mechanism of action of modified Juantan Prescription in the treatment of polycystic ovary syndrome(PCOS)based on network pharmacology and molecular docking.Methods:TCMSP database was used to obtain the effective constituents of the drugs in modified Juantan Prescription and their action targets;databases such as GeneCards and OMIM were used to obtain the targets associated with PCOS;Weishengxin platform was used to obtain the intersecting targets of modified Juantan Prescription and PCOS.Cytoscape 3.7.1 was used to construct a network of drugs,targets,and disease.STRING database was used to construct a protein-protein interaction network for the intersecting targets,and Metascape database was used to perform the gene ontology(GO)functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Molecular docking was used to validate the docking capability between key components and core targets.Results:A total of 96 active components were obtained,including kaempferol,stigmasterol,isorham-netin,wogonin,and naringenin;a total of 126 intersecting targets were obtained,including MAPK3,TP53,MAPK1,transcription factor AP-1,and protein kinase B1;the pathways obtained included the PI3K/AKT signaling pathway,the MAPK signaling pathway,the tumor necrosis factor signaling pathway,the transcription factor signaling pathway,and the AGE-RAGE signaling pathway.Quercetin bound well bound to 9 key targets,with the top 3 targets of MAPK3,TP53,and MAPK1.Conclusion:Modified Juantan Prescription has the features of multiple components,targets,and pathways in the treatment of PCOS and can exert regulatory and therapeutic effects on PCOS through the pharmacological actions such as improving insulin resistance,inhibiting granulosa cell autophagy and promoting follicular development,alleviating ovulatory dysfunction,promoting cell apoptosis,regulating blood glucose homeostasis and hormone levels,and anti-inflammation,which provides a theoretical basis for further research.