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In the present study, the anti-T. gondii effects of the natural flavonoid quercetin were evaluated using in vitro, ex vivo, and in silico models. Cell viability and intracellular proliferation of the parasite were determined via colorimetric assays. The lipid droplet assay was analyzed using Nile Red staining, the antioxidant and oxidative stress parameters were determined by biochemical assays, and the cytokine levels were quantified by immunoassays. Our results demonstrated that non-cytotoxic concentrations of quercetin (CC50 &gt; 100 \u03bcM) significantly inhibited parasite proliferation (IC50 = 14.10 \u00b1 2.83 \u03bcM; SI &gt; 7.09) in an irreversible manner. Quercetin impairs parasite adhesion, invasion, and reinfection capacity. In parallel, quercetin reduced lipid droplet accumulation, restored antioxidant balance by modulating redox biomarkers, and regulated cytokine production, notably increasing IL-4, IL-6, and IL-8 levels. Corroborating the in vitro findings, quercetin significantly reduced T. gondii proliferation in human placental villous explants while preserving tissue architecture and viability. In silico analyses revealed that quercetin binds to the active site of T. gondii hypoxanthine-guanine phosphoribosyltransferase (TgHGPRT) and exhibits favorable pharmacokinetic and drug-likeness properties.<\/jats:p>","DOI":"10.3390\/ijms27136054","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin Reduces Toxoplasma gondii Infection in In Vitro and Ex Vivo Placental Models"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5649-9645","authenticated-orcid":false,"given":"Muriel Pereira","family":"Souto","sequence":"first","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-317, 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