Icariin derivative inhibits inflammation through suppression of p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways

Biol Pharm Bull. 2010;33(8):1307-13. doi: 10.1248/bpb.33.1307.

Abstract

In this study we investigated the anti-inflammatory effects of an icariin derivative (3,5-dihydroxy-4'-methoxy-6'',6''-dimethy1-4'',5''-dihydropyrano[2'',3'':7,8]-flavone). We found that this icariin derivative inhibits tumor necrosis factor-alpha (TNF-alpha) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression, and protein expression in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. It also alleviates paw edema induced by carrageenan in mice. To clarify the molecular mechanisms underlying these anti-inflammatory effects, we examined the effects of this compound on the phosphorylation of mitogen-activated protein kinase (MAPK), phosphorylation of inhibitory kappaBalpha (IkappaBalpha), and nuclear translocation of p65 subunit of nuclear factor (NF)-kappaB, and found it suppresses the activation of p38 MAPK and inhibits translocation of NF-kappaB p65 to the nucleus through decreasing the phosphorylation of IkappaBalpha. As a result of these properties, this icariin derivative can be considered as a potential drug for inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blotting, Western
  • Cell Culture Techniques
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / biosynthesis
  • Edema / chemically induced
  • Edema / drug therapy
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Flavonoids / chemistry*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / biosynthesis
  • Protein Transport
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor RelA / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • 3,5-dihydroxy-4'-methoxy-6',6'-dimethyl-4',5'-dihydropyrano(2',3'-7,8)flavone
  • Anti-Inflammatory Agents, Non-Steroidal
  • Flavones
  • Flavonoids
  • Lipopolysaccharides
  • NF-kappa B
  • Transcription Factor RelA
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases
  • icariin