{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:37:09Z","timestamp":1789263429236,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o\u2014FAPEMA\/CAPES","award":["ACT-05691\/21"],"award-info":[{"award-number":["ACT-05691\/21"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o\u2014FAPEMA\/CAPES","award":["ACT-01784\/21"],"award-info":[{"award-number":["ACT-01784\/21"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o\u2014FAPEMA\/CAPES","award":["financial code 001"],"award-info":[{"award-number":["financial code 001"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o\u2014FAPEMA\/CAPES","award":["317186\/2023-0"],"award-info":[{"award-number":["317186\/2023-0"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o\u2014FAPEMA\/CAPES","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]},{"name":"CAPES\u2014Coordination for the Improvement of Higher Education Personnel","award":["ACT-05691\/21"],"award-info":[{"award-number":["ACT-05691\/21"]}]},{"name":"CAPES\u2014Coordination for the Improvement of Higher Education Personnel","award":["ACT-01784\/21"],"award-info":[{"award-number":["ACT-01784\/21"]}]},{"name":"CAPES\u2014Coordination for the Improvement of Higher Education Personnel","award":["financial code 001"],"award-info":[{"award-number":["financial code 001"]}]},{"name":"CAPES\u2014Coordination for the Improvement of Higher Education Personnel","award":["317186\/2023-0"],"award-info":[{"award-number":["317186\/2023-0"]}]},{"name":"CAPES\u2014Coordination for the Improvement of Higher Education Personnel","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["ACT-05691\/21"],"award-info":[{"award-number":["ACT-05691\/21"]}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["ACT-01784\/21"],"award-info":[{"award-number":["ACT-01784\/21"]}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["financial code 001"],"award-info":[{"award-number":["financial code 001"]}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["317186\/2023-0"],"award-info":[{"award-number":["317186\/2023-0"]}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Antifungal resistance to azoles, coupled with the increasing prevalence of Candida\u00a0albicans infections, represents a significant public health challenge and has driven the search for new natural compounds that can act as alternatives or adjuvants to the current antifungals. Ellagic acid (EA) has demonstrated antifungal activity; however, its effects are not fully understood. In this study, we investigated the in vitro anti-Candida activity of EA and its ability to potentiate the effects of fluconazole (FLZ) on C. albicans.\u00a0Methods: The Minimum Inhibitory Concentration (MIC) of EA was determined by broth microdilution and its interaction with FLZ was assessed using a checkerboard assay. Additionally, we examined the effects of EA on yeast-to-hypha transition, inhibition of biofilm formation, time\u2013kill kinetics, hemolytic activity, and cytotoxicity in HeLa ATCC\u00ae CCL-2\u2122 cells. Results: EA exhibited MIC values ranging from 250 to 2000 \u00b5g\/mL and showed synergistic and additive interactions with FLZ, resulting in a marked reduction in the MIC values of FLZ (up to 32-fold) and EA (up to 16-fold). In the time\u2013kill assay, the most effective combinations were 4\u00d7 EA MIC, 2\u00d7 EA MIC, and FIC EA + FLZ, which showed fungicidal activity. Furthermore, EA did not show hemolytic activity and demonstrated low and dose-dependent cytotoxicity in HeLa cells, with no cytotoxic effects observed in combination with FLZ. EA and the synergistic combination of EA and FLZ interfered with both the yeast-to-hypha transition process in C. albicans cells and biofilm formation. In addition to its antifungal efficacy, EA demonstrated a favorable safety profile at the concentrations used. Conclusions: This study presents promising results regarding the potential use of EA in combination with FLZ for the treatment of C. albicans infections.<\/jats:p>","DOI":"10.3390\/antibiotics13121174","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T04:47:22Z","timestamp":1733287642000},"page":"1174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ellagic Acid Potentiates the Inhibitory Effects of Fluconazole Against Candida albicans"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-996X","authenticated-orcid":false,"given":"Amanda Graziela Gon\u00e7alves","family":"Mendes","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-0662","authenticated-orcid":false,"given":"Carmem Duarte Lima","family":"Campos","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-3831","authenticated-orcid":false,"given":"Jos\u00e9 Lima","family":"Pereira-Filho","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-1973","authenticated-orcid":false,"given":"Aleania Polassa Almeida","family":"Pereira","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-9290","authenticated-orcid":false,"given":"Gabriel Silva Abrantes","family":"Reis","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9281-2676","authenticated-orcid":false,"given":"\u00c1rlon Wendel de Marinho Silva","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3879-5326","authenticated-orcid":false,"given":"Pablo de Matos","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4721-6824","authenticated-orcid":false,"given":"Fl\u00e1via Castello Branco","family":"Vidal","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4185-4577","authenticated-orcid":false,"given":"Silvio Gomes","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Fernandes","family":"da Silva Figueiredo","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Curitiba 80250-060, PR, Brazil"},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Biotecnologia Aplicada \u00e0 Sa\u00fade da Crian\u00e7a e do Adolescente, Faculdades Pequeno Pr\u00edncipe, Curitiba 80230-020, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-2514","authenticated-orcid":false,"given":"Elizabeth Soares","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Curitiba 80250-060, PR, Brazil"},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Biotecnologia Aplicada \u00e0 Sa\u00fade da Crian\u00e7a e do Adolescente, Faculdades Pequeno Pr\u00edncipe, Curitiba 80230-020, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-1101","authenticated-orcid":false,"given":"Cristina de Andrade","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Departamento de Biologia, Instituto Federal do Maranh\u00e3o, Av. Get\u00falio Vargas n\u00ba 2158\/2159, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2868-1314","authenticated-orcid":false,"given":"Val\u00e9rio","family":"Monteiro-Neto","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1021\/acs.chemrev.0c00199","article-title":"Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond","volume":"121","author":"Lee","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_2","unstructured":"WHO (2022). 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