{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:35:16Z","timestamp":1790436916324,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004482","name":"Kuwait University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004482","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp;amp; Exp Dental Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Antifungal drug resistance poses a major challenge in treating oral\n                      <jats:italic>Candida<\/jats:italic>\n                      infections. This study aimed to evaluate the antifungal activity of Honokiol, alone and combined with Fluconazole, against oral\n                      <jats:italic>Candida<\/jats:italic>\n                      isolates, and to investigate its mechanism of action via ergosterol biosynthesis inhibition and cell wall disruption.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      Susceptibility testing was performed using CLSI (M27\u2010A3) methodology on 16 oral\n                      <jats:italic>Candida<\/jats:italic>\n                      isolates, 8 endodontic isolates, and the reference strain ATCC 24433. Minimum inhibitory concentrations (MICs) of Honokiol and Fluconazole were determined alone and in combination. Ergosterol inhibitory assays and scanning electron microscopy (SEM) were used to assess cell wall integrity and morphological changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Honokiol exhibited MICs of 16\u201364\u2009\u00b5g\/mL (oral isolates), 16\u2009\u00b5g\/mL (endodontic isolates), and 32\u2009\u00b5g\/mL (ATCC 24433). In combination with Fluconazole, Honokiol's MICs decreased 4\u2010fold (4\u201316\u2009\u00b5g\/mL), while Fluconazole's MICs dropped 2\u2010 to 4\u2010fold (1\u201332\u2009\u00b5g\/mL). Synergy was confirmed by a 95.61% reduction in fungal growth (OD600) compared to controls. SEM revealed severe cell wall distortion, rupture, and cytoplasmic leakage. Honokiol significantly inhibited ergosterol biosynthesis, disrupting cellular integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Honokiol demonstrates potent antifungal activity against oral\n                      <jats:italic>Candida<\/jats:italic>\n                      isolates by targeting ergosterol biosynthesis and compromising cell wall integrity. Its synergistic enhancement of Fluconazole's effect suggests clinical potential as an adjunct therapy, potentially reducing resistance and lowering required drug doses in oral and endodontic candidiasis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cre2.70251","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:49:19Z","timestamp":1769694559000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic Antifungal Effects of Honokiol and Fluconazole Against Oral\n                    <i>Candida<\/i>\n                    : Implications for Managing Drug\u2010Resistant Infections"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8927-6617","authenticated-orcid":false,"given":"Maribasappa","family":"Karched","sequence":"first","affiliation":[{"name":"Oral Microbiology Laboratory, Department of Bioclinical 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