{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:01:18Z","timestamp":1792101678171,"version":"4.4.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["5R03DE031190-02"],"award-info":[{"award-number":["5R03DE031190-02"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Syzigium aromaticum<\/jats:italic> essential oil (EO), eugenol, and \u03b2-caryophyllene were evaluated regarding antifungal, antibiofilm, and <jats:italic>in vitro<\/jats:italic> toxicity. Additionally, <jats:italic>in vivo<\/jats:italic> toxicity of EO was observed. Anti-<jats:italic>Candida<\/jats:italic> activity was assessed through broth microdilution assay for all compounds. Time-kill assay (0, 1, 10, 30 min, 1, 2, and 4 h) was used to determine the influence of EO and eugenol on <jats:italic>Candida<\/jats:italic> Growth kinetics. Thereafter, both compounds were evaluated regarding their capacity to act on a biofilm formation and on mature biofilm, based on CFU\/ml\/g of dry weight. Cell Titer Blue Viability Assay was used for <jats:italic>in vitro<\/jats:italic> cytotoxicity, using oral epithelial cells (TR146) and human monocytes (THP-1). Lastly, <jats:italic>Galleria mellonella<\/jats:italic> model defined the EO <jats:italic>in vivo<\/jats:italic> acute toxicity. All compounds, except \u03b2-cariofilene (MIC &gt; 8000 \u03bcg\/ml), presented antifungal activity against <jats:italic>Candida<\/jats:italic> strains (MIC 500\u20131000 \u03bcg\/ml). The growth kinetics of <jats:italic>Candida<\/jats:italic> was affected by the EO (5xMIC 30 min onward; 10xMIC 10 min onward) and eugenol (5xMIC 10 min onward; 10xMIC 1 min onward). Fungal viability was also affected by 5xMIC and 10xMIC of both compounds during biofilm formation and upon mature biofilms. LD<jats:sub>50<\/jats:sub> was defined for TR146 and THP1 cells at, respectively, 59.37 and 79.54 \u03bcg\/ml for the EO and 55.35 and 84.16 \u03bcg\/ml for eugenol. No sign of toxicity was seen <jats:italic>in vivo<\/jats:italic> up to 10mg\/ml (20 x MIC) for the EO. <jats:italic>S<\/jats:italic>. <jats:italic>aromaticum<\/jats:italic> and eugenol presented antifungal and antibiofilm activity, with action on cell growth kinetics. <jats:italic>In vivo<\/jats:italic> acute toxicity showed a safe parameter for the EO up to 10 mg\/ml.<\/jats:p>","DOI":"10.1371\/journal.pone.0305405","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T17:32:02Z","timestamp":1718731922000},"page":"e0305405","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Syzygium aromaticum essential oil and its major constituents: Assessment of activity against Candida spp. and toxicity"],"prefix":"10.1371","volume":"19","author":[{"given":"Priscilla Guimar\u00e3es Silva","family":"Vasconcelos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Flores","family":"Abuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanda Paolla","family":"Raimundo e Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josean Fechine","family":"Tavares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edja Maria Melo de Brito","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8478-6981","authenticated-orcid":true,"given":"Ramiro Mendon\u00e7a","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"pone.0305405.ref001","first-page":"554","article-title":"Denture-related stomatitis in new complete denture wearers and its association with Candida species colonization: a prospective case-series","volume":"51","author":"MA Mousa","year":"2020","journal-title":"Quintessence Int (Berl)"},{"key":"pone.0305405.ref002","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1590\/1807-3107bor-2018.vol32.0092","article-title":"A single-center 18-year experience with oral candidiasis in Brazil: a retrospective study of 1,534 cases","volume":"32","author":"LC Reinhardt","year":"2018","journal-title":"Braz Oral Res"},{"key":"pone.0305405.ref003","doi-asserted-by":"crossref","first-page":"95","DOI":"10.17219\/dmp\/112861","article-title":"Current perspectives and the future of Candida albicans-associated denture stomatitis treatment","volume":"57","author":"MM Gad","year":"2020","journal-title":"Dent Med Probl"},{"key":"pone.0305405.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3402\/jom.v3i0.5771","article-title":"Pathogenesis and treatment of oral candidosis","volume":"3","author":"D Williams","year":"2011","journal-title":"J Oral Microbiol"},{"key":"pone.0305405.ref005","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/sj.bdj.2017.886","article-title":"Diagnosis and management of oral candidosis","volume":"223","author":"MAO Lewis","year":"2017","journal-title":"Br Dent J"},{"key":"pone.0305405.ref006","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.prosdent.2019.07.014","article-title":"The effect of overnight storage conditions on complete denture colonization by Candida albicans and dimensional stability: A systematic review","volume":"124","author":"V Verhaeghe T","year":"2020","journal-title":"J Prosthet Dent"},{"key":"pone.0305405.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/jof7020079","article-title":"Candida albicans-the virulence factors and clinical manifestations of infection","volume":"7","author":"J Talapko","year":"2021","journal-title":"J Fungi"},{"key":"pone.0305405.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/jof6010015","article-title":"Oral candidiasis: A disease of opportunity","volume":"6","author":"T Vila","year":"2020","journal-title":"J Fungi"},{"key":"pone.0305405.ref009","first-page":"20","article-title":"Management of Chronic Atrophic Candidiasis (Denture Stomatitis)-A Narrative Review","author":"E Abuhajar","year":"2023","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0305405.ref010","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"DJ Newman","year":"2020","journal-title":"J Nat Prod"},{"key":"pone.0305405.ref011","first-page":"10","article-title":"Syzygium aromaticum l. 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