A novel semisynthetic flavonoid 7-O-galloyltaxifolin upregulates heme oxygenase-1 in RAW264.7 cells via MAPK/Nrf2 pathway

J Med Chem. 2013 Feb 14;56(3):856-66. doi: 10.1021/jm3013344. Epub 2013 Jan 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • MAP Kinase Signaling System*
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Phosphorylation
  • Quercetin / analogs & derivatives*
  • Quercetin / chemistry
  • Quercetin / pharmacology
  • Up-Regulation*


  • 7-O-galloyltaxifolin
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Quercetin
  • Heme Oxygenase-1
  • Acetylcysteine