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Current therapies for congenital toxoplasmosis are limited by toxicity, long treatment regimens, and suboptimal efficacy, highlighting the urgent need for safer and more effective alternatives. In this study, we evaluated the antiparasitic effects of crude ethanolic extract of Brazilian Red Propolis (BRP) and its isolated compounds, focusing on 7-O-methylvestitol, in human trophoblast (BeWo) cells and third-trimester placental explants. Both BRP and 7-O-methylvestitol significantly reduced T. gondii adhesion, invasion, and intracellular replication, without compromising host cell viability. Ultrastructural analyses revealed irreversible parasite damage, and cytokine profiling demonstrated immunomodulatory effects, with enhanced production of interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF) in BeWo cells and downregulation of IL-6, MIF, and tumor Necrosis Factor (TNF) in infected placental villi. Notably, 7-O-methylvestitol reproduced and, in some assays, surpassed the antiparasitic activity of BRP, suggesting it as a key bioactive constituent responsible for the therapeutic potential of the extract. These findings support the identification of 7-O-methylvestitol as a promising lead compound for structure-based drug design and repositioning strategies, advancing the development of novel, safe, and targeted therapies against congenital toxoplasmosis.<\/jats:p>","DOI":"10.3390\/microorganisms13081937","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"1937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Brazilian Red Propolis and Its Active Constituent 7-O-methylvestitol Impair Early and Late Stages of Toxoplasma gondii Infection in Human Placental Models"],"prefix":"10.3390","volume":"13","author":[{"given":"Samuel Cota","family":"Teixeira","sequence":"first","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberl\u00e2ndia, Campus Umuarama, Av. 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Par\u00e1, 1720, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-2045","authenticated-orcid":false,"given":"Nagela Bernadelli Sousa","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Antimicrobial Testing, Institute of Biomedical Science, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-319, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6886-281X","authenticated-orcid":false,"given":"Joed Pires","family":"de Lima Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberl\u00e2ndia, Campus Umuarama, Av. 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Par\u00e1, 1720, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryani Felixa Fajardo","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberl\u00e2ndia, Campus Umuarama, Av. Par\u00e1, 1720, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3835-1925","authenticated-orcid":false,"given":"Marcos Paulo Oliveira","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberl\u00e2ndia, Campus Umuarama, Av. 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