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Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity

Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, a...

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Autores principales: Ivanov, Marija, Kannan, Abhilash, Stojković, Dejan S., Glamočlija, Jasmina, Calhelha, Ricardo C., Ferreira, Isabel C. F. R., Sanglard, Dominique, Soković, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824033/
https://www.ncbi.nlm.nih.gov/pubmed/33396973
http://dx.doi.org/10.3390/ph14010027
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author Ivanov, Marija
Kannan, Abhilash
Stojković, Dejan S.
Glamočlija, Jasmina
Calhelha, Ricardo C.
Ferreira, Isabel C. F. R.
Sanglard, Dominique
Soković, Marina
author_facet Ivanov, Marija
Kannan, Abhilash
Stojković, Dejan S.
Glamočlija, Jasmina
Calhelha, Ricardo C.
Ferreira, Isabel C. F. R.
Sanglard, Dominique
Soković, Marina
author_sort Ivanov, Marija
collection PubMed
description Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and apigetrin; these results indicate flavonoids’ indispensable capacity for further development as part of an anticandidal therapy or prevention strategy.
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spelling pubmed-78240332021-01-24 Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity Ivanov, Marija Kannan, Abhilash Stojković, Dejan S. Glamočlija, Jasmina Calhelha, Ricardo C. Ferreira, Isabel C. F. R. Sanglard, Dominique Soković, Marina Pharmaceuticals (Basel) Article Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and apigetrin; these results indicate flavonoids’ indispensable capacity for further development as part of an anticandidal therapy or prevention strategy. MDPI 2020-12-30 /pmc/articles/PMC7824033/ /pubmed/33396973 http://dx.doi.org/10.3390/ph14010027 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ivanov, Marija
Kannan, Abhilash
Stojković, Dejan S.
Glamočlija, Jasmina
Calhelha, Ricardo C.
Ferreira, Isabel C. F. R.
Sanglard, Dominique
Soković, Marina
Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity
title Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity
title_full Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity
title_fullStr Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity
title_full_unstemmed Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity
title_short Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity
title_sort flavones, flavonols, and glycosylated derivatives—impact on candida albicans growth and virulence, expression of cdr1 and erg11, cytotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824033/
https://www.ncbi.nlm.nih.gov/pubmed/33396973
http://dx.doi.org/10.3390/ph14010027
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