{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:58:35Z","timestamp":1792432715294,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Introduction:<\/jats:bold>\n Despite the rising concern with fungal resistance, a myriad of molecules has yet to be explored. Geraniol, linalool, and citronellal are monoterpenes with the same molecular formula (C\n 10<\/jats:sub>\n H\n 18<\/jats:sub>\n O), however, neither the effect of these compounds on inflammatory axis induced by\n Candida<\/jats:italic>\n spp. nor the antibiofilm Structure-Activity Relationship (SAR) have been well-investigated. Herein we analyzed geraniol, linalool and citronellal antifungal activity, cytotoxicity, and distinctive antibiofilm SAR, also the influence of geraniol on\n Candida<\/jats:italic>\n spp induced dysregulated inflammatory axis, and\n in vivo<\/jats:italic>\n toxicity.\n <\/jats:p>\n \n Methods:<\/jats:bold>\n Minimal inhibitory (MIC) and fungicidal (MFC) concentrations against\n Candida<\/jats:italic>\n spp were defined, followed by antibiofilm activity (CFU\u2013colony forming unit\/mL\/g of dry weight). Cytotoxic activity was assessed using human monocytes (THP-1) and oral squamous cell (TR146). Geraniol was selected for further analysis based on antifungal, antibiofilm and cytotoxic results. Geraniol was tested using a dual-chamber co-culture model with TR146 cells infected with\n C. albicans<\/jats:italic>\n , and THP-1 cells, used to mimic oral epithelium upon fungal infection. Expression of\n Candida<\/jats:italic>\n enzymes (phospholipase\u2013PLB and aspartyl proteases\u2013SAP) and host inflammatory cytokines (interleukins: IL-1\u03b2, IL-6, IL-17, IL-18, IL-10, and Tumor necrosis factor\u2013TNF) were analyzed. Lastly, geraniol\n in vivo<\/jats:italic>\n toxicity was assessed using\n Galleria mellonella<\/jats:italic>\n .\n <\/jats:p>\n \n Results:<\/jats:bold>\n MIC values obtained were 1.25\u20135\u00a0mM\/mL for geraniol, 25-100\u00a0mM\/mL for linalool, and 100\u2013200\u00a0mM\/mL for citronellal. Geraniol 5 and 50\u00a0mM\/mL reduced yeast viability during biofilm analysis, only 500\u00a0mM\/mL of linalool was effective against a 72\u00a0h biofilm and no biofilm activity was seen for citronellal. LD\n 50<\/jats:sub>\n for TR146 and THP-1 were, respectively: geraniol 5.883 and 8.027\u00a0mM\/mL; linalool 1.432 and 1.709\u00a0mM\/mL; and citronellal 0.3006 and 0.1825\u00a0mM\/mL. Geraniol was able to downregulate expression of fungal enzymes and host pro-inflammatory cytokines IL-1\u03b2, IL-6, and IL-18. Finally, safety\n in vivo<\/jats:italic>\n parameters were observed up to 20\u00a0mM\/Kg.\n <\/jats:p>\n \n Discussion:<\/jats:bold>\n Despite chemical similarities, geraniol presented better antifungal, antibiofilm activity, and lower cytotoxicity when compared to the other monoterpenes. It also showed low\n in vivo<\/jats:italic>\n toxicity and capacity to downregulate the expression of fungal enzymes and host pro-inflammatory cytokines. Thus, it can be highlighted as a viable option for oral candidiasis treatment.\n <\/jats:p>","DOI":"10.3389\/fphar.2024.1394053","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T06:34:56Z","timestamp":1721370896000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Monoterpene antifungal activities: evaluating geraniol, citronellal, and linalool on Candida biofilm, host inflammatory responses, and structure\u2013activity relationships"],"prefix":"10.3389","volume":"15","author":[{"given":"Priscilla Guimar\u00e3es Silva","family":"Vasconcelos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Flores","family":"Abuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edja Maria Melo Brito","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro Mendon\u00e7a","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.3390\/molecules28093669","article-title":"Potential effects of geraniol on cancer and inflammation-related diseases: a review of the recent research findings","volume":"28","author":"Ammar","year":"2023","journal-title":"Molecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.pestbp.2019.05.008","article-title":"Antimicrobial and antioxidant activities of hydrocarbon and oxygenated monoterpenes against some foodborne pathogens through in vitro and in silico studies","volume":"158","author":"Badawy","year":"2019","journal-title":"Pestic. 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