Inhibitory effect of N,N-didesmethylgrossularine-1 on inflammatory cytokine production in lipopolysaccharide-stimulated RAW 264.7 cells

Mar Drugs. 2009 Nov 17;7(4):589-99. doi: 10.3390/md7040589.

Abstract

N,N-Didesmethylgrossularine-1 (DDMG-1), a compound with a rare alpha-carboline structure, was isolated from an Indonesian ascidian Polycarpa aurata as responsible for the observed inhibitory activity against TNF-alpha production in lipopolysaccharide-stimulated murine macrophage-like RAW264.7 cells. DDMG-1 inhibited the mRNA level of mTNF-alpha, IkappaB-alpha degradation, and binding of NF-kappaB to the target DNA site in LPS-stimulated RAW 264.7 cells. Moreover, DDMG-1 had an inhibitory effect on the production of IL-8, which is produced in CD14(+)-THP-1 cells stimulated by LPS. DDMG-1 is thus a promising drug candidate lead compound for the treatment of chronic inflammatory diseases, such as rheumatoid arthritis.

Keywords: LPS; N,N-didesmethylgrossularine-1; NF-κB; RAW 264.7 cells; TNF-α; natural product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbolines / isolation & purification
  • Carbolines / pharmacology*
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis*
  • I-kappa B Proteins / metabolism
  • Interleukin-8 / biosynthesis
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • RNA, Messenger / biosynthesis
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Urochordata / chemistry*

Substances

  • Carbolines
  • Cytokines
  • I-kappa B Proteins
  • Interleukin-8
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • N,N-didesmethylgrossularine-1
  • NF-kappa B
  • Nfkbia protein, mouse
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha