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

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Title
Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-κB and c-Jun NH2-terminal kinase
Author(s)
Y H Kim; Sang-Han Lee; J Y Lee; S W Choi; J W Park; T K Kwon
Bibliographic Citation
European Journal of Pharmacology, vol. 494, no. 1, pp. 1-9
Publication Year
2004
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-κB (NF-κB) in these cells. Addition of triptolide inhibited phosphorylation of c-Jun NH2-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-κB. Taken together, these results suggest that triptolide acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of NF-κB and JNK activation.
Keyword
iNOSJNKNF-κBNO (Nitric oxide)triptolide
ISSN
0014-2999
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ejphar.2004.04.040
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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