Uncovering the Mechanism of Quercetin in the Treatment of Premature Ovarian Failure: A Multi-Faceted Approach Integrating Network Pharmacology, Bioinformatics Analysis and Experimental Validation.

Quercetin, a well-recognized antioxidant, has shown potential benefits for treating premature ovarian failure (POF). This study explores the effects of quercetin on POF using network pharmacology, differential expression genes (DEGs) analysis, and in vitro experiments. Firstly, we identified quercetin targets from the TCMSP database and retrieved POF-related targets from GeneCards, OMIM, PharmGKB, and Drugbank databases. We then identified common targets and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Additionally, we explored the DEGs of GSE193136 and its potential signaling pathways. In vitro experiments were conducted to examine the effect of quercetin pretreatment on cell proliferation and the PI3K/AKT signaling pathway in an H(2)O(2)-induced model. Network pharmacological analysis revealed that quercetin shares 113 common targets with POF, and GO and KEGG analyses suggested that the anti-POF effects of quercetin may be associated with the PI3K/AKT signaling pathway and oxidative stress response. The enrichment analysis of DEGs in the GSE193136 dataset further corroborated these findings. In vitro experiments demonstrated that quercetin significantly alleviated H(2)O(2)-induced apoptosis in KGN cells by inhibiting the expression of TP53, Caspase3, and Caspase9, followed by the enhancement of the phosphorylated expression of PI3K and AKT. This study indicates that quercetin inhibits KGN cell apoptosis by activating the PI3K/AKT signaling pathway, showing potential therapeutic benefits for POF, and may provide a theoretical basis for the application of quercetin in POF therapy.