Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 expression by xanthanolides isolated from Xanthium strumarium

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2179-82. doi: 10.1016/j.bmcl.2007.12.076. Epub 2008 Feb 2.

Abstract

Three sesquiterpenoids, xanthatin (1), xanthinosin (2), and 4-oxo-bedfordia acid (3) were isolated from Xanthium strumarium as inhibitors of nitric oxide synthesis in activated microglia (IC(50) values: 0.47, 11.2, 136.5 microM, respectively). Compounds 1 and 2 suppressed the expression of iNOS and COX-2 and the activity of NF-kappaB through the inhibition of LPS-induced I-kappaB-alpha degradation in microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism*
  • Furans / isolation & purification
  • Furans / pharmacology*
  • Gene Expression Regulation, Enzymologic
  • I-kappa B Kinase / metabolism
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Xanthium / chemistry*

Substances

  • 4-oxo-bedfordia acid
  • Furans
  • Lactones
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Sesquiterpenes
  • xanthinosin
  • xanthatin
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • I-kappa B Kinase