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Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells

The natural flavonoid quercetin is known to activate the transcription factor Nrf2, which regulates the expression of cytoprotective enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). In this study, a novel semisynthetic flavonoid 7-O-galloylquercetin (or quercetin-...

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Autores principales: Roubalová, Lenka, Biedermann, David, Papoušková, Barbora, Vacek, Jan, Kuzma, Marek, Křen, Vladimír, Ulrichová, Jitka, Dinkova-Kostova, Albena T., Vrba, Jiří
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148792/
https://www.ncbi.nlm.nih.gov/pubmed/27777014
http://dx.doi.org/10.1016/j.cbi.2016.10.015
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author Roubalová, Lenka
Biedermann, David
Papoušková, Barbora
Vacek, Jan
Kuzma, Marek
Křen, Vladimír
Ulrichová, Jitka
Dinkova-Kostova, Albena T.
Vrba, Jiří
author_facet Roubalová, Lenka
Biedermann, David
Papoušková, Barbora
Vacek, Jan
Kuzma, Marek
Křen, Vladimír
Ulrichová, Jitka
Dinkova-Kostova, Albena T.
Vrba, Jiří
author_sort Roubalová, Lenka
collection PubMed
description The natural flavonoid quercetin is known to activate the transcription factor Nrf2, which regulates the expression of cytoprotective enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). In this study, a novel semisynthetic flavonoid 7-O-galloylquercetin (or quercetin-7-gallate, 3) was prepared by direct galloylation of quercetin, and its effect on the Nrf2 pathway was examined. A luciferase reporter assay showed that 7-O-galloylquercetin, like quercetin, significantly activated transcription via the antioxidant response element in a stably transfected human AREc32 reporter cell line. In addition, 7-O-galloylquercetin caused the accumulation of Nrf2 and induced the expression of HO-1 at both the mRNA and protein levels in murine macrophage RAW264.7 cells. The induction of HO-1 by 7-O-galloylquercetin was significantly suppressed by N-acetyl-l-cysteine and SB203580, indicating the involvement of reactive oxygen species and p38 mitogen-activated protein kinase activity, respectively. HPLC/MS analyses also showed that 7-O-galloylquercetin was not degalloylated to quercetin, but it was conjugated with glucuronic acid and/or methylated in RAW264.7 cells. Furthermore, 7-O-galloylquercetin was found to increase the protein levels of Nrf2 and HO-1, and also the activity of NQO1 in murine hepatoma Hepa1c1c7 cells. Taken together, we conclude that 7-O-galloylquercetin increases Nrf2 activity and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells.
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spelling pubmed-51487922016-12-25 Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells Roubalová, Lenka Biedermann, David Papoušková, Barbora Vacek, Jan Kuzma, Marek Křen, Vladimír Ulrichová, Jitka Dinkova-Kostova, Albena T. Vrba, Jiří Chem Biol Interact Article The natural flavonoid quercetin is known to activate the transcription factor Nrf2, which regulates the expression of cytoprotective enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). In this study, a novel semisynthetic flavonoid 7-O-galloylquercetin (or quercetin-7-gallate, 3) was prepared by direct galloylation of quercetin, and its effect on the Nrf2 pathway was examined. A luciferase reporter assay showed that 7-O-galloylquercetin, like quercetin, significantly activated transcription via the antioxidant response element in a stably transfected human AREc32 reporter cell line. In addition, 7-O-galloylquercetin caused the accumulation of Nrf2 and induced the expression of HO-1 at both the mRNA and protein levels in murine macrophage RAW264.7 cells. The induction of HO-1 by 7-O-galloylquercetin was significantly suppressed by N-acetyl-l-cysteine and SB203580, indicating the involvement of reactive oxygen species and p38 mitogen-activated protein kinase activity, respectively. HPLC/MS analyses also showed that 7-O-galloylquercetin was not degalloylated to quercetin, but it was conjugated with glucuronic acid and/or methylated in RAW264.7 cells. Furthermore, 7-O-galloylquercetin was found to increase the protein levels of Nrf2 and HO-1, and also the activity of NQO1 in murine hepatoma Hepa1c1c7 cells. Taken together, we conclude that 7-O-galloylquercetin increases Nrf2 activity and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells. Elsevier 2016-12-25 /pmc/articles/PMC5148792/ /pubmed/27777014 http://dx.doi.org/10.1016/j.cbi.2016.10.015 Text en © 2016 The Authors. Published by Elsevier Ireland Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roubalová, Lenka
Biedermann, David
Papoušková, Barbora
Vacek, Jan
Kuzma, Marek
Křen, Vladimír
Ulrichová, Jitka
Dinkova-Kostova, Albena T.
Vrba, Jiří
Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells
title Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells
title_full Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells
title_fullStr Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells
title_full_unstemmed Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells
title_short Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells
title_sort semisynthetic flavonoid 7-o-galloylquercetin activates nrf2 and induces nrf2-dependent gene expression in raw264.7 and hepa1c1c7 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148792/
https://www.ncbi.nlm.nih.gov/pubmed/27777014
http://dx.doi.org/10.1016/j.cbi.2016.10.015
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