基于网络药理学和分子对接探讨褪黑素治疗多囊卵巢综合征的作用机制

Mechanism of melatonin in treatment of polycystic ovary syndrome based on network pharmacology and molecular docking

目的基于网络药理学方法和分子对接技术探讨褪黑素治疗多囊卵巢综合征的作用机制。方法使用PubChem、Swiss Target Prediction、Pharm Mapper、DrugBank、TCMSP数据库筛选褪黑素作用靶点,GeneCards、OMIM、DisGeNET数检索多囊卵巢综合征相关靶点,使用韦恩图工具取交集,获得褪黑素与多囊卵巢综合征的共同靶点。构建靶点蛋白互相作用(PPI)网络,并筛选核心靶点,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,使用Cytoscape 3.7.1构建褪黑素治疗多囊卵巢综合征的“靶点–信号通路”网络图。选择主要靶标与褪黑素进行分子对接评价结合性。结果褪黑素中109个有效靶点作用于多囊卵巢综合征,关键核心靶点为SRC、PIK3R1、PIK3CA、EGFR、HRAS、RHOA、ERBB2、IGF1、MET、JAK2。富集的GO生物过程主要包括腺体发育、磷脂酰肌醇介导信号素、蛋白激酶B信号传导等,富集的KEGG通路主要包括黏着斑、胰岛素信号通路、趋化因子信号通路、孕酮–介导卵母细胞成熟等。分子对接结果显示,褪黑素与核心靶点PIK3R1、PIK3CA、EGFR、HRAS、RHOA、ERBB2、MET、JAK2结合较好。结论褪黑素可能通过抗凋亡、调节代谢、抑制炎症反应、抗氧化应激等作用改善多囊卵巢综合征。

Objective To explore the mechanism of melatonin in treatment of polycystic ovary syndrome based on network pharmacology and molecular docking technology.Methods PubChem,Swiss Target Prediction,Pharm Mapper,DrugBank,TCMSP were used to screen melatonin targets.GeneCards,OMIM,DisGeNET databases were used to obtain polycystic ovary syndrome related targets.The Venn diagram tool was used to obtain the common target of melatonin and polycystic ovary syndrome.The target protein interaction(PPI)network was constructed,and the core targets were screened,and the gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed.Cytoscape 3.7.1 was used to construct the“target-signaling pathway”network map of melatonin treatment in polycystic ovary syndrome.The main target and melatonin were selected for molecular docking evaluation.Results 109 Effective targets of melatonin act on polycystic ovary syndrome,and the key core targets are SRC,PIK3R1,PIK3CA,EGFR,HRAS,RHOA,ERBB2,IGF1,MET,and JAK2.The enriched GO biological processes mainly included gland development,phosphtidylinositol mediated signaling hormone,protein kinase B signaling,etc.The enriched KEGG pathways mainly included adhesion plaque,insulin signaling pathway,chemokine signaling pathway,progesterone-mediated oocyte maturation,etc.Molecular docking results showed that melatonin binds well to the core targets PIK3R1,PIK3CA,EGFR,HRAS,RHOA,ERBB2,MET,and JAK2.Conclusion Melatonin may improve polycystic ovary syndrome by anti-apoptosis,regulating metabolism,inhibiting inflammation and anti-oxidative stress.