{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:04:03Z","timestamp":1787061843591,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prince of Songkla University Ph.D. Scholarship, Faculty of Medicine at Prince of Songkla University, Thailand"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ellagic acid (EA) is a phenolic phytochemical found in many plants and their fruits. Vaginal epithelial cells are the first line of defense against pathogen invasion in the female reproductive tract and express antimicrobial peptides, including hBD2 and SLPI. This study investigated the in vitro effects of EA (1) on vaginal innate immunity using human vaginal epithelial cells, and (2) on HPV16 pseudovirus infection. Vaginal cells were cultured in the presence or absence of EA, and the expression of hBD2 and SLPI was determined at both transcriptional and translational levels. In addition, secretion of various cytokines and chemokines was measured. Cytotoxicity of EA was determined by CellTiter-blue and MTT assays. To investigate the ability of EA to inhibit HPV16 infection, EA was used to treat HEK-293FT cells in pre-attachment and adsorption steps. We found significant increases in both hBD2 mRNA (mean 2.9-fold at 12.5 \u00b5M EA, p &lt; 0.001) and protein (mean 7.1-fold at 12.5 \u00b5M EA, p = 0.002) in response to EA. SLPI mRNA also increased significantly (mean 1.4-fold at 25 \u00b5M EA, p = 0.01), but SLPI protein did not. Secretion of IL-2 but not of other cytokines\/chemokines was induced by EA in a dose-dependent manner. EA was not cytotoxic. At the pre-attachment step, EA at CC20 and CC50 showed a slight trend towards inhibiting HPV16 pseudovirus, but this was not significant. In summary, vaginal epithelial cells can respond to EA by producing innate immune factors, and at tested concentrations, EA is not cytotoxic. Thus, plant-derived EA could be useful as an immunomodulatory agent to improve vaginal health.<\/jats:p>","DOI":"10.3390\/molecules29153630","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T17:16:49Z","timestamp":1722446209000},"page":"3630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Ellagic Acid on Vaginal Innate Immune Mediators and HPV16 Infection In Vitro"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2618-4939","authenticated-orcid":false,"given":"Aornrutai","family":"Promsong","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Princess of Naradhiwas University, Narathiwat 96000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-7050","authenticated-orcid":false,"given":"Jureeporn","family":"Chuerduangphui","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-211X","authenticated-orcid":false,"given":"Claire N.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0375-2764","authenticated-orcid":false,"given":"Florian","family":"Hladik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-7463","authenticated-orcid":false,"given":"Surada","family":"Satthakarn","sequence":"additional","affiliation":[{"name":"Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-8858","authenticated-orcid":false,"given":"Wipawee","family":"Nittayananta","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Thammasat University, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"da Silva, R.L., da Silva Batista, Z., Bastos, G.R., Cunha, A.P.A., Figueiredo, F.V., de Castro, L.O., Dos Anjos Pereira, L., da Silva, M., Vidal, F.C.B., and Barros, M.C. 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