Saucerneol D, a naturally occurring sesquilignan, inhibits LPS-induced iNOS expression in RAW264.7 cells by blocking NF-kappaB and MAPK activation

Int Immunopharmacol. 2008 Oct;8(10):1395-400. doi: 10.1016/j.intimp.2008.05.009. Epub 2008 Jun 20.

Abstract

We evaluated the ability of saucerneol D (SD), a tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, to regulate the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells. SD consistently inhibited nitric oxide (NO) production in a dose-dependent manner, with an IC(50) of 2.62 microM, and also blocked LPS-induced iNOS expression. SD potently suppressed both the reporter gene expression and DNA-binding activity of nuclear factor-kappaB (NF-kappaB). In addition, SD inhibited IkappaB-alpha degradation in a concentration- and time-dependent manner. SD also inhibited LPS-induced activation of various mitogen-activated protein kinases, including extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). These findings suggest that SD may inhibit LPS-induced iNOS expression by blocking NF-kappaB and MAPK activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression / drug effects*
  • Lignans / pharmacology
  • Lipopolysaccharides / toxicity
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • NF-kappa B / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / biosynthesis*

Substances

  • Lignans
  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide Synthase Type II
  • Mitogen-Activated Protein Kinases