{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T01:45:49Z","timestamp":1786671949896,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/08730-6"],"award-info":[{"award-number":["2016\/08730-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Commensal yeast from the genus Candida is part of the healthy human microbiota. In some cases, Candida spp. dysbiosis can result in candidiasis, the symptoms of which may vary from mild localized rashes to severe disseminated infections. The most prevalent treatments against candidiasis involve fluconazole, itraconazole, miconazole, and caspofungin. Moreover, amphotericin B associated with prolonged azole administration is utilized to control severe cases. Currently, numerous guidelines recommend echinocandins to treat invasive candidiasis. However, resistance to these antifungal drugs has increased dramatically over recent years. Considering this situation, new therapeutic alternatives should be studied to control candidiasis, which has become a major medical concern. Limonene belongs to the group of terpene molecules, known for their pharmacological properties. In this study, we evaluated in vitro the limonene concentration capable of inhibiting the growth of yeast from the genus Candida susceptible or resistant to antifungal drugs and its capacity to induce fungal damage. In addition, intravaginal fungal infection assays using a murine model infected by Candida albicans were carried out and the fungal burden, histopathology, and scanning electron microscopy were evaluated. All of our results suggest that limonene may play a protective role against the infection process by yeast from the genus Candida.<\/jats:p>","DOI":"10.3390\/jof6030183","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T09:40:56Z","timestamp":1600767656000},"page":"183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["In Vitro and In Vivo Inhibitory Activity of Limonene against Different Isolates of Candida spp."],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4495-7077","authenticated-orcid":false,"given":"Juli\u00e1n E.","family":"Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Studies in Translational Microbiology and Emerging Diseases Research Group (MICROS), School of Medicine and Health Sciences, Universidad del Rosario, Bogot\u00e1 D.C 111221, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1385-1501","authenticated-orcid":false,"given":"Diego C. P.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biomedical Sciences Institute, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7297-0784","authenticated-orcid":false,"given":"Daniela L.","family":"Jabes","sequence":"additional","affiliation":[{"name":"N\u00facleo Integrado de Biotecnologia, Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes-SP 08780-911, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-2307","authenticated-orcid":false,"given":"David Aciole","family":"Barbosa","sequence":"additional","affiliation":[{"name":"N\u00facleo Integrado de Biotecnologia, Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes-SP 08780-911, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda F. M.","family":"Cunha","sequence":"additional","affiliation":[{"name":"N\u00facleo Integrado de Biotecnologia, Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes-SP 08780-911, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9619-269X","authenticated-orcid":false,"given":"Luiz R.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias Naturais e Humanas, Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09210-580, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise C.","family":"Arruda","sequence":"additional","affiliation":[{"name":"N\u00facleo Integrado de Biotecnologia, Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes-SP 08780-911, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-9809","authenticated-orcid":false,"given":"Carlos","family":"Pelleschi Taborda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biomedical Sciences Institute, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-060, Brazil"},{"name":"Laboratory of Medical Mycology, Institute of Tropical Medicine of S\u00e3o Paulo-LIM53\/Medical School, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S1473-3099(10)70218-8","article-title":"Emerging opportunistic yeast infections","volume":"11","author":"Miceli","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alvarez-Moreno, C., Cortes, J., and Denning, D. (2018). Burden of Fungal Infections in Colombia. J. Fungi, 4.","DOI":"10.3390\/jof4020041"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vila, T., Sultan, A.S., Montelongo-Jauregui, D., and Jabra-Rizk, M.A. (2020). Oral candidiasis: A disease of opportunity. J. Fungi, 6.","DOI":"10.3390\/jof6010015"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1128\/MMBR.00045-10","article-title":"Regulatory circuitry governing fungal development, drug resistance, and disease","volume":"75","author":"Shapiro","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1128\/AAC.49.5.1679-1687.2005","article-title":"Antileishmanial Activity of the Terpene Nerolidol","volume":"49","author":"Arruda","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7949","DOI":"10.1016\/j.bmc.2009.10.019","article-title":"Antiprotozoal, anticancer and antimicrobial activities of dihydroartemisinin acetal dimers and monomers","volume":"17","author":"Slade","year":"2009","journal-title":"Bioorganic Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbrc.2011.06.176","article-title":"\u03b1-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model","volume":"411","author":"Matsuo","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.2217\/fmb.09.98","article-title":"Cellular interactions of farnesol, a quorum-sensing molecule produced by Candida albicans","volume":"4","author":"Langford","year":"2009","journal-title":"Future Microbiol."},{"key":"ref_9","first-page":"355","article-title":"Atomic Force Microscopy in Biomedical Research","volume":"736","author":"Ricci","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/carcin\/9.2.331","article-title":"Anti-carcinogenic activity of d-limonene during the initiation and promotion\/progression stages of dmba-induced rat mammary carcinogenesis","volume":"9","author":"Elson","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.2147\/OTT.S155716","article-title":"D-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer","volume":"11","author":"Yu","year":"2018","journal-title":"Onco. Targets. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yang, C., Chen, H., Chen, H., Zhong, B., Luo, X., and Chun, J. (2017). Antioxidant and anticancer activities of essential oil from gannan navel orange peel. Molecules, 22.","DOI":"10.3390\/molecules22081391"},{"key":"ref_13","first-page":"4021","article-title":"Limonene-induced Regression of Mammary Carcinomas","volume":"52","author":"Haag","year":"1992","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.intimp.2004.12.012","article-title":"Effect of D-limonene on immune response in BALB\/c mice with lymphoma","volume":"5","year":"2005","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.3748\/wjg.v10.i14.2140","article-title":"Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene","volume":"10","author":"Lu","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/bcpt.12010","article-title":"Protective Effects of d-Limonene on Lipid Peroxidation and Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rats","volume":"112","author":"Murali","year":"2013","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"395","DOI":"10.5650\/jos.59.395","article-title":"Effect of limonene on permeation enhancement of ketoprofen in palm oil esters nanoemulsion","volume":"59","author":"Sakeena","year":"2010","journal-title":"J. Oleo Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2174\/156720108783330970","article-title":"Limonene Enhances the In Vitro and In Vivo Permeation of Trimetazidine Across a Membrane-Controlled Transdermal Therapeutic System","volume":"5","author":"Krishnaiah","year":"2008","journal-title":"Curr. Drug Deliv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1128\/AAC.48.7.2502-2509.2004","article-title":"Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum","volume":"48","author":"Goulart","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.biopha.2009.02.004","article-title":"Inhibitory activity of limonene against Leishmania parasites in vitro and in vivo","volume":"63","author":"Arruda","year":"2009","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-018-2293-7","article-title":"Induction of programmed cell death in Trypanosoma cruzi by Lippia alba essential oils and their major and synergistic terpenes (citral, limonene and caryophyllene oxide)","volume":"18","author":"Moreno","year":"2018","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3177\/jnsv.48.155","article-title":"Distribution and immune responses resulting from oral administration of D-limonene in rats","volume":"48","author":"Hamada","year":"2002","journal-title":"J. Nutr. Sci. Vitaminol. (Tokyo)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/15287398709530961","article-title":"Modulation of immune responses in mice by d-limonene","volume":"20","author":"Evans","year":"1987","journal-title":"J. Toxicol. Environ. Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/j.1439-0507.2004.00994.x","article-title":"Estrogen-dependent induction of persistent vaginal candidosis in naive mice. Ostrogen-abhangige Induktion der persistierenden Vaginalcandidose in naiven Mausen","volume":"47","author":"Hamad","year":"2004","journal-title":"Mycoses"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3389\/fmicb.2017.00771","article-title":"Antifungal activity of the biphosphinic cyclopalladate C7a against Candida albicans yeast forms in vitro and in vivo","volume":"8","author":"Rossi","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35018","DOI":"10.1038\/srep35018","article-title":"A Naturally Occurring Antibody Fragment Neutralizes Infectivity of Diverse Infectious Agents","volume":"6","author":"Polonelli","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.fct.2018.07.052","article-title":"Review of toxicological assessment of d-limonene, a food and cosmetics additive","volume":"120","author":"Ravichandran","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/BF00686281","article-title":"Human metabolism of the experimental cancer therapeutic agent d-limonene","volume":"35","author":"Crowell","year":"1994","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/7158756","article-title":"Antifungal Activity of Essential Oils against Candida albicans Strains Isolated from Users of Dental Prostheses","volume":"2017","author":"Freire","year":"2017","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Leite, M.C.A., De Brito Bezerra, A.P., De Sousa, J.P., Guerra, F.Q.S., and De Oliveira Lima, E. (2014). Evaluation of antifungal activity and mechanism of action of citral against Candida albicans. Evid.-Based Complement. Altern. Med.","DOI":"10.1093\/mmy\/myu078"},{"key":"ref_31","first-page":"565","article-title":"Limonene inhibits Candida albicans growth by inducing apoptosis","volume":"56","author":"Thakre","year":"2018","journal-title":"Med. Mycol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/jac\/dkg202","article-title":"In vitro and in vivo activity of tea tree oil against azole-susceptible and -resistant human pathogenic yeasts","volume":"51","author":"Mondello","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12905-019-0748-8","article-title":"Current patient perspectives of vulvovaginal candidiasis: Incidence, symptoms, management and post-treatment outcomes","volume":"19","author":"Yano","year":"2019","journal-title":"BMC Womens. Health"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/1471-0528.12994","article-title":"Vulvovaginal Candida albicans infections: Pathogenesis, immunity and vaccine prospects","volume":"122","author":"Cassone","year":"2015","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1086\/377234","article-title":"Relation between Recurrent Vulvovaginal Candidiasis, Vaginal Concentrations of Mannose-Binding Lectin, and a Mannose-Binding Lectin Gene Polymorphism in Latvian Women","volume":"37","author":"Babula","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"285","DOI":"10.33594\/000000139","article-title":"Short-Term Antifungal Treatments of Caprylic Acid with Carvacrol or Thymol Induce Synergistic 6-Log Reduction of Pathogenic Candida albicans by Cell Membrane Disruption and Efflux Pump Inhibition","volume":"53","author":"Bae","year":"2019","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_37","first-page":"259","article-title":"D-limonene: Safety and clinical applications","volume":"12","author":"Sun","year":"2007","journal-title":"Altern. Med. Rev."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/6\/3\/183\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:14Z","timestamp":1760177534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/6\/3\/183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,22]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["jof6030183"],"URL":"https:\/\/doi.org\/10.3390\/jof6030183","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,22]]}}}