Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , |
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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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:29462024-08-05T22:33:27.857078Repositório 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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1808129436983230464 |