Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells
| العنوان: | Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells |
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| المؤلفون: | Lenka, Roubalová, David, Biedermann, Barbora, Papoušková, Jan, Vacek, Marek, Kuzma, Vladimír, Křen, Jitka, Ulrichová, Albena T, Dinkova-Kostova, Jiří, Vrba |
| المصدر: | Chemico-Biological Interactions |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Cell Survival, NF-E2-Related Factor 2, NQO1, NAD(P)H:quinone oxidoreductase 1, Methyl gallate, ARE, antioxidant response element, Gapdh, glyceraldehyde-3-phosphate dehydrogenase, DMSO, dimethyl sulfoxide, p38 Mitogen-Activated Protein Kinases, Mass Spectrometry, Article, Nrf2, Mice, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, ROS, reactive oxygen species, ERK, extracellular signal-regulated kinase, Genes, Reporter, Cell Line, Tumor, Quercetin-7-gallate, HO-1/Hmox1, heme oxygenase-1, NAD(P)H Dehydrogenase (Quinone), Animals, Humans, heterocyclic compounds, Nrf2, NF-E2 p45-related factor 2, Protein Kinase Inhibitors, Biotransformation, NAC, N-acetyl-l-cysteine, GCLM, glutamate-cysteine ligase modifier subunit, Keap1, Kelch-like ECH-associated protein 1, RAW 264.7 Cells, Metabolism, Gene Expression Regulation, Heme oxygenase-1, Enzyme Induction, JNK, c-Jun N-terminal kinase, Metabolome, p38 MAPK, p38 mitogen-activated protein kinase, Quercetin, Reactive Oxygen Species, GCLC, glutamate-cysteine ligase catalytic subunit, MAPK, mitogen-activated protein kinase |
| الوصف: | 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. Graphical abstract Image 1 Highlights • A novel semisynthetic flavonoid was prepared: 7-O-galloylquercetin (3). • 3 activates Nrf2/antioxidant response element in AREc32 reporter cells. • 3 increases Nrf2 and Nrf2-regulated proteins in RAW264.7 and Hepa1c1c7 cells. • 3 is not hydrolyzed, but it is glucuronidated and/or methylated in RAW264.7 cells. |
| تدمد: | 1872-7786 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::7e6fbf86ca95d28c7e05d0f312bfa175Test https://pubmed.ncbi.nlm.nih.gov/27777014Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........7e6fbf86ca95d28c7e05d0f312bfa175 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18727786 |
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