A novel semisynthetic flavonoid 7-O-galloyltaxifolin upregulates heme oxygenase-1 in RAW264.7 cells via MAPK/Nrf2 pathway
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23294286
DOI
10.1021/jm3013344
Knihovny.cz E-resources
- MeSH
- Acetylcysteine pharmacology MeSH
- Cell Line MeSH
- NF-E2-Related Factor 2 metabolism MeSH
- Phosphorylation MeSH
- Heme Oxygenase-1 genetics metabolism MeSH
- MAP Kinase Signaling System * MeSH
- Mice MeSH
- Quercetin analogs & derivatives chemistry pharmacology MeSH
- Gene Expression Regulation, Enzymologic drug effects MeSH
- Up-Regulation * MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 7-O-galloyltaxifolin MeSH Browser
- Acetylcysteine MeSH
- NF-E2-Related Factor 2 MeSH
- Heme Oxygenase-1 MeSH
- Nfe2l2 protein, mouse MeSH Browser
- Quercetin MeSH
Quercetin and gallic acid are natural activators of the transcription factor Nrf2, which regulates the expression of many cytoprotective enzymes including heme oxygenase-1 (HO-1). We developed procedures for the synthesis of monogalloyl esters of quercetin and taxifolin (dihydroquercetin), namely, 3-O-galloylquercetin and 7-O-galloyltaxifolin, and examined their effect on the Nrf2 pathway in RAW264.7 cells. Unlike quercetin and free gallic acid, 3-O-galloylquercetin and natural quercetin derivatives isoquercitrin (quercetin-3-O-β-d-glucoside) and taxifolin had no effect on the expression of HO-1. In contrast, 7-O-galloyltaxifolin increased both mRNA and protein levels of HO-1 at concentrations of 25 μM and above. The induction of HO-1 by 7-O-galloyltaxifolin was primarily associated with the production of reactive oxygen species and phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPKs and ERKs, followed by nuclear accumulation of Nrf2 and downregulation of Keap1, a negative regulator of Nrf2. We conclude that 7-O-galloyltaxifolin upregulates HO-1 via activation of the MAPK/Nrf2 signaling pathway.
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