Inhibitory effects of nardostachin on nitric oxide, prostaglandin E2, and tumor necrosis factor-alpha production in lipopolysaccharide activated macrophages

Biol Pharm Bull. 2003 Oct;26(10):1375-8. doi: 10.1248/bpb.26.1375.

Abstract

Nardostachin, which is an iridoid isolated from Patrinia saniculaefolia, was examined by assessing its effect on the production of tumor necrosis factor-alpha (TNF-alpha) and expression of 2 enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. This compound consistently inhibited the production of nitric oxide (NO) and TNF-alpha production in a dose-dependent manner, with respective IC(50) values of 12.3 and 16.2 microM. The decrease in quantity of NO products was accompanied by a decrease in the iNOS protein level, as assessed by Western blotting probed with specific anti-iNOS antibodies. In addition, this compound also reduced the COX-2 protein expression level and the attendant PGE(2) production in LPS-stimulated macrophages. These results suggest that nardostachin may be useful for inhibiting the production of inflammatory mediators such as TNF-alpha, NO and PGE(2) in inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 2
  • Dinoprostone / antagonists & inhibitors*
  • Dinoprostone / metabolism
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Patrinia
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Structures
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Diterpenes
  • Isoenzymes
  • Lipopolysaccharides
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • nardostachin
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone