Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.

Detalhes bibliográficos
Autor(a) principal: Dantas-Medeiros, Renato
Data de Publicação: 2021
Outros Autores: Zanatta, Ana Caroline [UNESP], de Souza, Luanda Bárbara Ferreira Canário, Fernandes, Júlia Morais, Amorim-Carmo, Bruno, Torres-Rêgo, Manoela, Fernandes-Pedrosa, Matheus de Freitas, Vilegas, Wagner [UNESP], Araújo, Thiago Antǒnio de Sousa, Michel, Sylvie, Grougnet, Raphaël, Chaves, Guilherme Maranhão, Zucolotto, Silvana Maria
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3389/fmicb.2021.613155
http://hdl.handle.net/11449/208495
Resumo: Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31–1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole.
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spelling Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.biofilmBurseraceaefungal infectionsherbal drugimburananatural antifungalresistanceCommiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31–1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Laboratory of Pharmacognosy Department of Pharmaceutical Sciences Faculty of Pharmacy Federal University of Rio Grande do NorteLaboratory of Bioprospecting of Natural Products São Paulo State University (UNESP)Laboratory of Phytochemistry Institute of Chemistry São Paulo State University (UNESP)Laboratory of Medical and Molecular Mycology Department of Clinical and Toxicological Analyses Federal University of Rio Grande do NorteLaboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar) Faculty of Pharmacy Federal University of Rio Grande do NorteDepartment of Health University Center of Maurício de NassauLaboratory of Pharmacognosy Faculty of Pharmacy University Paris DescartesLaboratory of Bioprospecting of Natural Products São Paulo State University (UNESP)Laboratory of Phytochemistry Institute of Chemistry São Paulo State University (UNESP)Federal University of Rio Grande do NorteUniversidade Estadual Paulista (Unesp)University Center of Maurício de NassauUniversity Paris DescartesDantas-Medeiros, RenatoZanatta, Ana Caroline [UNESP]de Souza, Luanda Bárbara Ferreira CanárioFernandes, Júlia MoraisAmorim-Carmo, BrunoTorres-Rêgo, ManoelaFernandes-Pedrosa, Matheus de FreitasVilegas, Wagner [UNESP]Araújo, Thiago Antǒnio de SousaMichel, SylvieGrougnet, RaphaëlChaves, Guilherme MaranhãoZucolotto, Silvana Maria2021-06-25T11:13:00Z2021-06-25T11:13:00Z2021-02-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fmicb.2021.613155Frontiers in Microbiology, v. 12.1664-302Xhttp://hdl.handle.net/11449/20849510.3389/fmicb.2021.6131552-s2.0-85102254000Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Microbiologyinfo:eu-repo/semantics/openAccess2021-10-23T19:02:13Zoai:repositorio.unesp.br:11449/208495Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T19:02:13Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
title Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
spellingShingle Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
Dantas-Medeiros, Renato
biofilm
Burseraceae
fungal infections
herbal drug
imburana
natural antifungal
resistance
title_short Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
title_full Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
title_fullStr Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
title_full_unstemmed Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
title_sort Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
author Dantas-Medeiros, Renato
author_facet Dantas-Medeiros, Renato
Zanatta, Ana Caroline [UNESP]
de Souza, Luanda Bárbara Ferreira Canário
Fernandes, Júlia Morais
Amorim-Carmo, Bruno
Torres-Rêgo, Manoela
Fernandes-Pedrosa, Matheus de Freitas
Vilegas, Wagner [UNESP]
Araújo, Thiago Antǒnio de Sousa
Michel, Sylvie
Grougnet, Raphaël
Chaves, Guilherme Maranhão
Zucolotto, Silvana Maria
author_role author
author2 Zanatta, Ana Caroline [UNESP]
de Souza, Luanda Bárbara Ferreira Canário
Fernandes, Júlia Morais
Amorim-Carmo, Bruno
Torres-Rêgo, Manoela
Fernandes-Pedrosa, Matheus de Freitas
Vilegas, Wagner [UNESP]
Araújo, Thiago Antǒnio de Sousa
Michel, Sylvie
Grougnet, Raphaël
Chaves, Guilherme Maranhão
Zucolotto, Silvana Maria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Federal University of Rio Grande do Norte
Universidade Estadual Paulista (Unesp)
University Center of Maurício de Nassau
University Paris Descartes
dc.contributor.author.fl_str_mv Dantas-Medeiros, Renato
Zanatta, Ana Caroline [UNESP]
de Souza, Luanda Bárbara Ferreira Canário
Fernandes, Júlia Morais
Amorim-Carmo, Bruno
Torres-Rêgo, Manoela
Fernandes-Pedrosa, Matheus de Freitas
Vilegas, Wagner [UNESP]
Araújo, Thiago Antǒnio de Sousa
Michel, Sylvie
Grougnet, Raphaël
Chaves, Guilherme Maranhão
Zucolotto, Silvana Maria
dc.subject.por.fl_str_mv biofilm
Burseraceae
fungal infections
herbal drug
imburana
natural antifungal
resistance
topic biofilm
Burseraceae
fungal infections
herbal drug
imburana
natural antifungal
resistance
description Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31–1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole.
publishDate 2021
dc.date.none.fl_str_mv 2021-06-25T11:13:00Z
2021-06-25T11:13:00Z
2021-02-22
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fmicb.2021.613155
Frontiers in Microbiology, v. 12.
1664-302X
http://hdl.handle.net/11449/208495
10.3389/fmicb.2021.613155
2-s2.0-85102254000
url http://dx.doi.org/10.3389/fmicb.2021.613155
http://hdl.handle.net/11449/208495
identifier_str_mv Frontiers in Microbiology, v. 12.
1664-302X
10.3389/fmicb.2021.613155
2-s2.0-85102254000
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers in Microbiology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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