Dihydroquercetin (DHQ) induced HO-1 and NQO1 expression against oxidative stress through the Nrf2-dependent antioxidant pathway

J Agric Food Chem. 2013 Mar 20;61(11):2755-61. doi: 10.1021/jf304768p. Epub 2013 Mar 5.

Abstract

Dihydroquercetin (DHQ) is a well-known antioxidant agent. In the present investigation, we reported for the first time that DHQ stimulates the expression of phase II detoxifying enzymes through the Nrf2-dependent signaling pathway. The IC50 values of DHQ for reduction of 2,2-diphenyl-1-picrylhydrazol (DPPH), reducing power assay, lipid peroxidation assay, and xanthine oxidase inhibition were 5.96, 4.31, 2.03, and 13.24 μM, respectively. DHQ possessed considerable protective activity from oxidative DNA damage. A luciferase reporter assay also demonstrated that DHQ-activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to the ARE (antioxidant response element) enhancer sequence. Furthermore, Western blotting and luciferase assay revealed DHQ activated ERK1/2, Akt, and JNK signaling pathways, subsequently leading to Nrf2 nuclear translocation. DHQ upregulated the Nrf2-related antioxidant genes heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), and glutamate-cysteine ligase modifier subunits. Inhibition of Nrf2 by siRNA reduced DHQ-induced upregulation of these antioxidant genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidant Response Elements
  • Antioxidants / pharmacology*
  • Heme Oxygenase-1 / genetics*
  • Heme Oxygenase-1 / metabolism
  • Hep G2 Cells
  • Humans
  • Larix / chemistry*
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects*
  • Plant Extracts / pharmacology*
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • Signal Transduction / drug effects
  • Transcriptional Activation / drug effects
  • Up-Regulation / drug effects*

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Plant Extracts
  • Quercetin
  • taxifolin
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human