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Vitisin A suppresses LPS-induced NO production by inhibiting ERK, p38, and NF-kappaB activation in RAW 264.7 cells.

Abstract
Vitisin A, a resveratrol tetramer isolated from Vitis vinifera roots, exhibits antioxidative, anticancer, antiapoptotic, and anti-inflammatory effects. It also inhibits nitric oxide (NO) production. Here, we examined the mechanism by which vitisin A inhibits NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. Vitisin A dose dependently inhibited LPS-induced NO production and inducible NO synthase (iNOS) expression. In contrast, the production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was not altered by vitisin A. To investigate the signaling pathway for NO inhibition by vitisin A, we examined nuclear factor-kappaB (NF-kappaB) activation in the mitogen-activated protein kinase (MAPK) pathway, an inflammation-induced signal pathway in RAW 264.7 cells. Vitisin A inhibited LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 phosphorylation and suppressed LPS-induced NF-kappaB activation in RAW 264.7 cells. This suggests that vitisin A decreased NO production via downregulation of ERK1/2 and p38 and the NF-kappaB signal pathway in RAW 264.7 cells.
Authors Mi Jeong Sung, Munkhtugs Davaatseren, Won Kim, Sung Kwang Park, Soon-Hee Kim, Haeng Jeon Hur, Myung Sunny Kim, Young-Sup Kim, Dae Young Kwon
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 9 Issue 3 Pg. 319-23 (Mar 2009) ISSN: 1878-1705 [Electronic] Netherlands
PMID19135555 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzofurans
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Phenols
  • Tumor Necrosis Factor-alpha
  • vitisin A
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Benzofurans (chemistry, pharmacology)
  • Cell Line
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
  • Interleukin-6 (metabolism)
  • Lipopolysaccharides (immunology)
  • Macrophages (drug effects, immunology)
  • Mice
  • NF-kappa B (antagonists & inhibitors, metabolism)
  • Nitric Oxide (antagonists & inhibitors, biosynthesis)
  • Nitric Oxide Synthase Type II (antagonists & inhibitors, metabolism)
  • Phenols (chemistry, pharmacology)
  • Phosphorylation (drug effects, physiology)
  • Signal Transduction (drug effects, physiology)
  • Tumor Necrosis Factor-alpha (metabolism)
  • p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)

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