Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-kappa B and c-Jun NH2-terminal kinase.

Abstract

Triptolide (PG490) is a natural, biologically active compound extracted from the Chinese herb Tripterygium wilfordii. It has been shown to possess potent anti-inflammatory and immunosuppressive properties. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, triptolide inhibits nitric oxide (NO) production in a dose-dependent manner and abrogates inducible nitric oxide synthase (iNOS) gene expression. To investigate the mechanism by which triptolide inhibits murine iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAP kinases) and nuclear factor-kappa B (NF-kappa B) in these cells. Addition of triptolide inhibited phosphorylation of c-Jun NH(2)-terminal kinase (JNK) but not that of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase. In addition, triptolide significantly inhibited the DNA binding activity of NF-kappa B. Taken together, these results suggest that triptolide acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of NF-kappa B and JNK activation.

• Authors: Young-Ho Kim, Sang-Han Lee, Jai-Youl Lee, Sang-Won Choi, Jong-Wook Park, Taeg Kyu Kwon
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 494 Issue 1 Pg. 1-9 (Jun 21 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15194445 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• Enzyme Inhibitors
• Epoxy Compounds
• Lipopolysaccharides
• NF-kappa B
• Phenanthrenes
• triptolide
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Cell Line
• Diterpenes (chemistry, pharmacology)
• Down-Regulation (drug effects, physiology)
• Enzyme Inhibitors (pharmacology)
• Epoxy Compounds
• Gene Expression Regulation, Enzymologic (drug effects, physiology)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• Mice
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors, biosynthesis, genetics)
• Nitric Oxide Synthase Type II
• Phenanthrenes (chemistry, pharmacology)