A sesquiterpene, dehydrocostus lactone, inhibits the expression of inducible nitric oxide synthase and TNF-alpha in LPS-activated macrophages

Planta Med. 1999 Mar;65(2):104-8. doi: 10.1055/s-1999-13968.

Abstract

Nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) are the major mediators produced in activated macrophages which contribute to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (dehydrocostus lactone) isolated from the medicinal plant, Saussurea lappa, inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW 264.7 cells by suppressing inducible nitric oxide synthase enzyme expression. This compound also decreased the TNF-alpha level in LPS-activated systems in vitro and in vivo. Thus, dehydrocostus lactone may be a possible candidate for the development of new drugs to treat endotoxemia accompanied by the overproduction of NO and TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Enzyme Inhibitors / pharmacology*
  • Lactones / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II
  • Sesquiterpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Lactones
  • Lipopolysaccharides
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • dehydrocostus lactone
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse