{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:45:43Z","timestamp":1789177543269,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de S. Paulo","award":["2018\/02333-0"],"award-info":[{"award-number":["2018\/02333-0"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de S. Paulo","award":["2017\/26517-0"],"award-info":[{"award-number":["2017\/26517-0"]}]},{"name":"funda\u00e7\u00e3o de Amparo a Pesquisa do Estados de S. Paulo","award":["#2018\/20828-7"],"award-info":[{"award-number":["#2018\/20828-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Candidiasis therapy, especially for candidiasis caused by Candida non-albicans species, is limited by the relatively reduced number of antifungal drugs and the emergence of antifungal tolerance. This study evaluates the anticandidal activity of 41 plant-derived products against Candida species, in both planktonic and biofilm cells. This study also evaluates the toxicity and the therapeutic action of the most active compounds by using the Caenorhabditis elegans\u2013Candida model. The planktonic cells were cultured with various concentrations of the tested agents. The Cupressus sempervirens, Citrus limon, and Litsea cubeba essential oils as well as gallic acid were the most active anticandidal compounds. Candida cell re-growth after treatment with these agents for 48 h demonstrated that the L. cubeba essential oil and gallic acid displayed fungistatic activity, whereas the C. limon and C. sempervirens essential oils exhibited fungicidal activity. The C. sempervirens essential oil was not toxic and increased the survival of C. elegans worms infected with C. glabrata or C. orthopsilosis. All the plant-derived products assayed at 250 \u00b5g\/mL affected C. krusei biofilms. The tested plant-derived products proved to be potential therapeutic agents against Candida, especially Candida non-albicans species, and should be considered when developing new anticandidal agents.<\/jats:p>","DOI":"10.3390\/plants8110494","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T04:07:07Z","timestamp":1573531627000},"page":"494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["In Vitro and In Vivo Anti-Candida spp. Activity of Plant-Derived Products"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-5754","authenticated-orcid":false,"given":"Reginaldo dos Santos","family":"Pedroso","sequence":"first","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"},{"name":"Escola T\u00e9cnica de Sa\u00fade, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda Lorena","family":"Balbino","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9ssica","family":"Andrade","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cecilia Pereira Sacardo","family":"Dias","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tavane Aparecida","family":"Alvarenga","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita C\u00e1ssia Nascimento","family":"Pedroso","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia Pereira","family":"Pimenta","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Lucarini","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1831-0050","authenticated-orcid":false,"given":"Patr\u00edcia Mendon\u00e7a","family":"Pauletti","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Helena","family":"Janu\u00e1rio","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco T\u00falio Menezes","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Minas Gerais, Passos 37902-407, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-572X","authenticated-orcid":false,"given":"Mayker Lazaro Dantas","family":"Miranda","sequence":"additional","affiliation":[{"name":"Instituto Federal do Tri\u00e2ngulo Mineiro, Campus Uberl\u00e2ndia Centro, Uberl\u00e2ndia 38.064-300, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-5951","authenticated-orcid":false,"given":"Regina Helena","family":"Pires","sequence":"additional","affiliation":[{"name":"Universidade de Franca, Franca 14404-600, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1128\/IAI.02843-14","article-title":"Clinical implications of oral candidiasis: Host tissue damage and disseminated bacterial disease","volume":"83","author":"Kong","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1080\/14656566.2018.1476490","article-title":"Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species","volume":"19","author":"Sobel","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Friedman, D.Z.P., and Schwartz, I.S. (2019). Emerging fungal infections: New patients, new patterns, and new pathogens. J. Fungi, 5.","DOI":"10.3390\/jof5030067"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fanning, S., and Mitchell, A.P. (2012). Fungal biofilms. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002585"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Asong, J.A., Amoo, S.O., McGaw, L.J., Nkadimeng, S.M., Aremu, A.O., and Otang-Mbeng, W. (2019). Antimicrobial activity, antioxidant potential, cytotoxicity and phytochemical profiling of four plants locally used against skin diseases. Plants, 8.","DOI":"10.3390\/plants8090350"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Serra, E., Hidalgo-Bastida, L., Verran, J., Williams, D., and Malic, S. (2018). Antifungal activity of commercial essential oils and biocides against Candida albicans. Pathogens, 7.","DOI":"10.3390\/pathogens7010015"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.phymed.2011.03.008","article-title":"Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle","volume":"18","author":"Zore","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nazzaro, F., Fratianni, F., Coppola, R., and De Feo, V. (2017). Essential oils and antifungal activity. Pharmaceuticals, 10.","DOI":"10.3390\/ph10040086"},{"key":"ref_10","first-page":"6697","article-title":"Flavonoids and phenolic acids: Role and biochemical activity in plants and humans","volume":"5","author":"Ghasemzadeh","year":"2011","journal-title":"J. Med. Plants Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural products as sources of new drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jsps.2013.11.002","article-title":"Alternatives to animal testing: A review","volume":"23","author":"Doke","year":"2015","journal-title":"Saudi Pharm. J."},{"key":"ref_13","unstructured":"Brazil Ministry of Health, Minister\u2019s Office (2019, July 09). Ordinance No. 971, May 3th, 2006: Approves the National Policy for Integrative and Complementary Practices (Pol\u00edtica Nacional de Pr\u00e1ticas Integrativas e Complementares [PNPIC]) in the Single Health System (Sistema \u00danico de Sa\u00fade\u2014SUS), Available online: http:\/\/bvsms.saude.gov.br\/bvs\/publicacoes\/pnpic.pdf."},{"key":"ref_14","unstructured":"Republic Presidence, Deputy Chief of Legal Affairs (2019, July 09). Ordinance No. 5813, 22 July 2006: Approves the National Policy of Medicinal Plants and Herbal Medicines and Other Measures, Available online: http:\/\/www.planalto.gov.br\/ccivil_03\/_Ato2004-2006\/2006\/Decreto\/D5813.htm."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Selim, S.A., Adam, M.E., Hassan, S.M., and Albalawi, A.R. (2014). Chemical composition, antimicrobial and antibiofilm activity of the essential oil and methanol extract of the Mediterranean cypress (Cupressus sempervirens L.). BMC Complement Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-179"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s10600-009-9356-4","article-title":"Constituents and biological activity of the chloroform extract and essential oil of Cupressus sempervirens L.","volume":"45","author":"Ibrahim","year":"2009","journal-title":"Chem. Nat. Compd."},{"key":"ref_17","first-page":"63","article-title":"In vitro antimicrobial activities of some Iranian conifers","volume":"12","author":"Afsharzadeh","year":"2013","journal-title":"Iran J. Pharm. Res."},{"key":"ref_18","first-page":"329","article-title":"Chemical composition and biological potential of essential oil from Tunisian Cupressus sempervirens L.","volume":"22","author":"Boukhris","year":"2012","journal-title":"J. Arid Land Stud."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a019778","DOI":"10.1101\/cshperspect.a019778","article-title":"The Candida pathogenic species complex","volume":"4","author":"Turner","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.bjm.2015.05.001","article-title":"Candida glabrata among Candida spp. from environmental health practitioners of a Brazilian Hospital","volume":"47","author":"Savastano","year":"2016","journal-title":"Braz. J. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1590\/S0074-02762011000600002","article-title":"Candida parapsilosis complex water isolates from a haemodialysis unit: Biofilm production and in vitro evaluation of the use of clinical antifungals","volume":"106","author":"Pires","year":"2011","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"378280","DOI":"10.1155\/2014\/378280","article-title":"Evaluation of antifungal activity and mechanism of action of citral against Candida albicans","volume":"2014","author":"Leite","year":"2014","journal-title":"Evid. Based Complement Alternat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1590\/S0103-50532009001000006","article-title":"Composition and antimicrobial activity of essential oils from Poiretia bahiana C. M\u00fcller (Papilionoideae-Leguminosae)","volume":"20","author":"Araujo","year":"2009","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1046\/j.1365-2672.2003.02059.x","article-title":"Antifungal activity of the components of Melaleuca alternifolia (tea tree) oil","volume":"95","author":"Hammer","year":"2003","journal-title":"J. Appl. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1128\/AAC.50.2.674-684.2006","article-title":"Pharmacokinetic-pharmacodynamic comparison of amphotericin B (AMB) and two lipid-associated AMB preparations, liposomal AMB and AMB lipid complex, in murine candidiasis models","volume":"50","author":"Andes","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.20473\/j.djmkg.v50.i1.p43-48","article-title":"Effects of Citrus limon essential oil (Citrus limon L.) on cytomorphometric changes of Candida albicans","volume":"50","author":"Prabajati","year":"2017","journal-title":"Dent. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1590\/S1516-05722013000500011","article-title":"Chemical constituents and toxicological studies of the essential oil extracted from Citrus limon Burn (Rutaceae)","volume":"15","author":"Campelo","year":"2013","journal-title":"Rev. Bras. Pl. Med."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1080\/03601234.2012.716686","article-title":"Nematicidal activity of terpenoids","volume":"48","author":"Alaniz","year":"2013","journal-title":"J. Env. Sci. Health B."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12950","DOI":"10.3390\/molecules171112950","article-title":"Antibacterial, antifungal and cytotoxic isoquinoline alkaloids from Litsea cubeba","volume":"17","author":"Zhang","year":"2012","journal-title":"Molecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fphar.2016.00198","article-title":"Chemical composition and anti-candidiasis mediated wound healing property of Cymbopogon nardus essential oil on chronic diabetic wounds","volume":"7","author":"Kandimalla","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kamle, M., Mahato, D.K., Lee, K.E., Bajpai, V.K., Gajurel, P.R., Gu, K.S., and Kumar, P. (2019). Ethnopharmacological properties and medicinal uses of Litsea cubeba. Plants, 8.","DOI":"10.3390\/plants8060150"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/ptr.5823","article-title":"Antifungal activity of gallic acid in vitro and in vivo","volume":"31","author":"Li","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3389\/fmicb.2018.00647","article-title":"Effects of acetone fraction from Buchenavia tomentosa aqueous extract and gallic acid on Candida albicans biofilms and virulence factors","volume":"9","author":"Teodoro","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/ptr.6222","article-title":"Histone acetylation increases in response to ferulic, gallic, and sinapic acids acting synergistically in vitro to inhibit Candida albicans yeast-to-hyphae transition","volume":"33","author":"Shi","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.4155\/fmc-2017-0096","article-title":"Activity of gallic acid and its ester derivatives in Caenorhabditis elegans and zebrafish (Danio rerio) models","volume":"9","author":"Singulani","year":"2019","journal-title":"Future Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jdent.2016.09.001","article-title":"Essential oils-containing mouthwashes for gingivitis and plaque: Meta-analyses and meta-regression","volume":"55","author":"Haas","year":"2016","journal-title":"J. Dent."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103575","DOI":"10.1016\/j.micpath.2019.103575","article-title":"Characterization of oral candidiasis and the Candida species profile in patients with oral mucosal diseases","volume":"134","author":"Hu","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_39","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2012). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, CLSI. Fourth Informational Supplement, Document M27-S4."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.mycmed.2018.04.007","article-title":"Efficacy of modified Leeming-Notman media in a resazurin microtiter assay in the evaluation of in-vitro activity of fluconazole against Malassezia furfur ATCC 14521","volume":"28","author":"Far","year":"2018","journal-title":"J. Mycol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1590\/S0036-46652015000700011","article-title":"Susceptibility test for fungi: Clinical and laboratorial correlations in medical mycology","volume":"57","author":"Melhem","year":"2015","journal-title":"Rev. Inst. Med. Trop. S. Paulo"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1590\/S0074-02762002000700017","article-title":"Screening of some plants used in the Brazilian folk medicine for the treatment of infectious diseases","volume":"97","author":"Holetz","year":"2002","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/0972060X.2019.1626293","article-title":"Chemical composition, in vitro trypanocidal and antibacterial activities of the essential oil from the dried leaves of Eugenia dysenterica DC from Brazil","volume":"22","author":"Santos","year":"2019","journal-title":"J. Essent. Oil Bear. Plants"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0732-8893(02)00525-4","article-title":"Minimum fungicidal concentrations of amphotericin B for bloodstream Candida species","volume":"45","author":"Viudes","year":"2003","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/nprot.2008.141","article-title":"A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing","volume":"3","author":"Pierce","year":"2008","journal-title":"Nat. Prot."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Scorzoni, L., de Lucas, M.P., Mesa-Arango, A.C., Fusco-Almeida, A.M., Lozano, E., Cuenca-Estrella, M., Mendes-Giannini, M.J., and Zaragoza, O. (2013). Antifungal efficacy during Candida krusei infection in non-conventional models correlates with the yeast in vitro susceptibility profile. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060047"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1038\/nprot.2008.193","article-title":"C. elegans-based, whole animal, in vivo screen for the identification of antifungal compounds","volume":"3","author":"Tampakakis","year":"2008","journal-title":"Nat. Protoc."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/8\/11\/494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:33:37Z","timestamp":1760189617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/8\/11\/494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,11]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["plants8110494"],"URL":"https:\/\/doi.org\/10.3390\/plants8110494","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,11]]}}}