The Preventive Effects of Quercetin on Preterm Birth Based on Network Pharmacology and Bioinformatics.

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.