The Preventive Effects of Quercetin on Preterm Birth Based on Network Pharmacology and Bioinformatics
The Preventive Effects of Quercetin on Preterm Birth Based on Network Pharmacology and Bioinformatics
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基于网络药理学和生物信息学的槲皮素对早产的预防作用
DOI：
10.1007/s43032-021-00674-4
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发表时间：
2021-07-06
影响因子：
2.9
通讯作者：
Zhang，Weishe
中科院分区：
文献类型：
--
作者：
Zhang，Jiejie;Peng，Qiaozhen;Zhang，Weishe
我们以前的研究表明，槲皮素预防脂多糖诱导的早产。本研究旨在阐明槲皮素预防早产的潜在作用靶点和生物学机制。我们使用生物信息学数据库收集槲皮素和早产的候选靶标。通过基因本体论和京都基因百科全书和基因组途径富集分析，分析交叉靶点的生物学功能和富集途径。然后，通过cytoscape插件cytoHubba从蛋白质-蛋白质相互作用网络中识别中心靶标。我们获得了105个槲皮素预防早产的靶点。交叉靶点的生物学过程主要涉及甾体代谢过程、药物代谢过程、氧化还原过程、omega-羟化酶P450通路、细胞迁移的正向调节、凋亡过程的负向调节和细胞增殖的正向调节。高度富集的途径是类固醇激素的生物合成，通过细胞色素P450代谢外源性物质，蛋白多糖在癌症中，粘着斑，和花生四烯酸代谢。槲皮素在预防早产中的10个中心靶点是AKT丝氨酸/苏氨酸激酶1、促分裂原活化蛋白激酶3、表皮生长因子受体、胰高血糖素-内过氧化物合酶2、促分裂原活化蛋白激酶1、雌激素受体1、热休克蛋白90 α家族A类成员1、促分裂原活化蛋白激酶8、雄激素受体和基质金属肽酶9。分子对接分析表明，这些蛋白质与槲皮素之间有良好的结合。总之，这些发现突出了槲皮素预防早产的关键靶点和分子机制。
Our previous study has shown that quercetin prevented lipopolysaccharide-induced preterm birth. This study aims to clarify the potential targets and biological mechanisms of quercetin in preventing preterm birth. We used bioinformatics databases to collect the candidate targets for quercetin and preterm birth. The biological functions and enriched pathways of the intersecting targets were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein-protein interaction network. We obtained 105 targets for quercetin in preventing preterm birth. The biological processes of the intersecting targets are mainly involved in steroid metabolic process, drug metabolic process, oxidation-reduction process, omega-hydroxylase P450 pathway, positive regulation of cell migration, negative regulation of apoptotic process, and positive regulation of cell proliferation. The highly enriched pathways were steroid hormone biosynthesis, metabolism of xenobiotics by cytochrome P450, proteoglycans in cancer, focal adhesion, and arachidonic acid metabolism. The ten hub targets for quercetin in preventing preterm birth were AKT serine/threonine kinase 1, mitogen-activated protein kinase 3, epidermal growth factor receptor, prostaglandin-endoperoxide synthase 2, mitogen-activated protein kinase 1, estrogen receptor 1, heat shock protein 90 alpha family class A member 1, mitogen-activated protein kinase 8, androgen receptor, and matrix metallopeptidase 9. Molecular docking analysis showed good bindings between these proteins and quercetin. In conclusion, these findings highlight the key targets and molecular mechanisms of quercetin in preventing preterm birth.