基于网络药理学和分子对接技术探究青蒿素对多囊卵巢综合征的潜在治疗机制

Exploration on the potential therapeutic mechanism of artemisinin in polycystic ovary syndrome based on network pharmacology and molecular docking technology

目的应用网络药理学和分子对接技术探索青蒿素对多囊卵巢综合征(polycystic ovary syndrome,PCOS)的潜在作用机制。方法通过Pubchem、Swiss Target Prediction、PharmMapper数据库预测青蒿素作用靶点,利用GeneCard、DisGeNET数据库获取与PCOS有关靶点;应用韦恩图分析青蒿素与PCOS的交集靶点;利用String软件对交集靶点进行PPI蛋白网络互作分析,并利用Cytoscape软件进行核心靶点筛选;应用DAVID数据库进行基因本体(gene ontology,GO)功能、京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析,并借助在线软件对分析结果进行可视化;通过Chemdraw、PyMol、Auto Dock Tools软件及RCSB PDB数据库对青蒿素及核心靶蛋白进行分子对接。结果得到青蒿素靶点229个,PCOS靶点1292个,韦恩图分析交集靶点90个,潜在核心靶点5个,分别为丝氨酸/苏氨酸蛋白激酶(serine/threonine-protein kinase,AKT1)、雌激素受体(estrogen receptor 1,ESR1)、基质金属蛋白酶(matrix metalloprotein 9,MMP9)、过氧化物酶体增殖激活受体(peroxisome proliferator-activated receptor gamma,PPARγ)、基质金属蛋白酶(matrix metalloprotein 2,MMP2),主要涉及磷脂酰肌醇-3-激酶(phosphoinositide 3-kinase,PI3K)-蛋白激酶B(protein kinase B,Akt)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、Ras、内分泌抵抗等信号通路。分子对接结果显示青蒿素与对应核心靶蛋白之间存在分子结合位点。结论初步预测分析青蒿素可能通过多靶点、多机制对PCOS发挥治疗作用。

Objective To explore the potential mechanism of artemisinin in the treatment of polycystic ovary syndrome(PCOS)by network pharmacology and molecular docking technology.Methods The corresponding targets of natural product artemisinin were obtained from PubChem,Swiss Target Prediction and PharmMapper databases,targets related to PCOS were obtained through GeneCards and DisGeNET databases;the intersection target genes of Artemisinin and PCOS were screened by Draw Venn diagram.Then the protein-protein interaction network(PPI)was constructed according to the intersection target genes through the STRING Database,and the core targets were screened by Cytoscape.Besides,gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis was performed by DAVID Database,and finally the data were analyzed visually by the online platform.Molecular docking of artemisinin and core targets were performed by Chemdraw,Pymol,Auto Dock Tools and RCSB PDB database.Results A total of 229 targets of artemisinin and 1292 targets of PCOS were screened out,90 overlapping targets were obtained by Draw Venn diagram,and 5 potential core targets,AKT1,ESR1,MMP9,PPARG,MMP2,were mainly act on PI3K Akt,MAPK,RAS,endocrine resistance and other signal pathways.Molecular docking results showed that there were molecular binding sites between artemisinin and core targets.Conclusion It is preliminarily analyzed that artemisinin may play a therapeutic role in PCOS through multiple targets and mechanisms.