Distinct inhibitory mechanisms of isoquercitrin gallate and its aglycone on zymosan-induced peroxynitrite production in macrophages

Nitric Oxide. 2007 Nov-Dec;17(3-4):134-42. doi: 10.1016/j.niox.2007.06.002. Epub 2007 Jun 21.

Abstract

Peroxynitrite, the coupling product of superoxide and nitric oxide (NO) radicals, plays as a pathogenic mediator in the oxidative stress-implicated diseases. Quercetin 3-O-beta-(2''galloyl)-glucopyranoside (Q-32) is an isoquercitrin gallate. In this study, Q-32 was found to inhibit zymosan-induced production of protein-bound 3-nitrotyrosine, a stable metabolite of peroxynitrite, in macrophages RAW 264.7, and its inhibitory mechanism was also documented to be different from that of its aglycone, quercetin. Both Q-32 and quercetin inhibited not only zymosan- but also phorbol 12-myristate 13-acetate-induced superoxide productions in the macrophages. Q-32 did not affect NO production and inducible NO synthase (iNOS) expression in zymosan-stimulated macrophages RAW 2647. However, quercetin inhibited zymosan-induced NO production as well as down-regulated zymosan-induced iNOS expression at the transcription level. Further, quercetin inhibited zymosan-induced nuclear factor (NF)-kappaB transcriptional activity but also NF-kappaB-dependent iNOS promoter activity. Taken together, Q-32 and quercetin could provide invaluable tools to investigate zymosan-induced oxidative stress with distinct antioxidant mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Benzopyrans / pharmacology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gallic Acid / chemistry
  • Gene Expression / drug effects
  • I-kappa B Kinase / genetics
  • Luciferases / genetics
  • Luciferases / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Peroxynitrous Acid / metabolism*
  • Protein Kinase C-delta / antagonists & inhibitors
  • Protein Kinase C-delta / chemistry
  • Pyrrolidines / pharmacology
  • Quercetin / analogs & derivatives
  • Quercetin / chemistry
  • Quercetin / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superoxides / chemistry
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thiocarbamates / pharmacology
  • Transfection
  • Zymosan / pharmacology*

Substances

  • Acetophenones
  • Antioxidants
  • Benzopyrans
  • Enzyme Inhibitors
  • NF-kappa B
  • Pyrrolidines
  • Thiocarbamates
  • isoquercitrin
  • Superoxides
  • Peroxynitrous Acid
  • pyrrolidine dithiocarbamic acid
  • Nitric Oxide
  • Gallic Acid
  • Zymosan
  • Quercetin
  • rottlerin
  • Luciferases
  • Nitric Oxide Synthase Type II
  • Prkcd protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • Protein Kinase C-delta
  • Tetradecanoylphorbol Acetate