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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| Vydáno v: | Pharmaceuticals (Basel, Switzerland) Ročník 14; číslo 1; s. 27 |
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30.12.2020
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| Abstract | 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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| AbstractList | 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. 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.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. 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 ( ) and ergosterol biosynthesis enzyme ( ) 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 with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, apigetrin, and quercitrin has downregulated . Contrary to rutin and apigenin, isoquercitrin has upregulated . 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. |
| Author | Ivanov, Marija Stojković, Dejan S. Glamočlija, Jasmina Sanglard, Dominique Kannan, Abhilash Calhelha, Ricardo C. Soković, Marina Ferreira, Isabel C. F. R. |
| AuthorAffiliation | 3 Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; calhelha@ipb.pt (R.C.C.); iferreira@ipb.pt (I.C.F.R.F.) 1 Department of Plant Physiology, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia; marija.smiljkovic@ibiss.bg.ac.rs (M.I.); dejanbio@ibiss.bg.ac.rs (D.S.S.); jasna@ibiss.bg.ac.rs (J.G.) 2 Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Rue du Bugnon 48, 1011 Lausanne, Switzerland; abhilifescizurich@gmail.com (A.K.); dominique.sanglard@chuv.ch (D.S.) |
| AuthorAffiliation_xml | – name: 2 Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Rue du Bugnon 48, 1011 Lausanne, Switzerland; abhilifescizurich@gmail.com (A.K.); dominique.sanglard@chuv.ch (D.S.) – name: 1 Department of Plant Physiology, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia; marija.smiljkovic@ibiss.bg.ac.rs (M.I.); dejanbio@ibiss.bg.ac.rs (D.S.S.); jasna@ibiss.bg.ac.rs (J.G.) – name: 3 Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; calhelha@ipb.pt (R.C.C.); iferreira@ipb.pt (I.C.F.R.F.) |
| Author_xml | – sequence: 1 givenname: Marija orcidid: 0000-0002-2480-5490 surname: Ivanov fullname: Ivanov, Marija – sequence: 2 givenname: Abhilash surname: Kannan fullname: Kannan, Abhilash – sequence: 3 givenname: Dejan S. orcidid: 0000-0002-4159-1471 surname: Stojković fullname: Stojković, Dejan S. – sequence: 4 givenname: Jasmina orcidid: 0000-0001-6823-1137 surname: Glamočlija fullname: Glamočlija, Jasmina – sequence: 5 givenname: Ricardo C. orcidid: 0000-0002-6801-4578 surname: Calhelha fullname: Calhelha, Ricardo C. – sequence: 6 givenname: Isabel C. F. R. orcidid: 0000-0003-4910-4882 surname: Ferreira fullname: Ferreira, Isabel C. F. R. – sequence: 7 givenname: Dominique surname: Sanglard fullname: Sanglard, Dominique – sequence: 8 givenname: Marina orcidid: 0000-0002-7381-756X surname: Soković fullname: Soković, Marina |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33396973$$D View this record in MEDLINE/PubMed |
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| Keywords | antifungal biofilm flavonoids efflux pumps cytotoxicity isoquercitrin antivirulence |
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