Abstract |
Nuclear factor kappaB ( NF-kappaB) activation by NF-kappaB-inducing kinase (NIK)- IkappaB alpha kinase (IKK) pathway and mitogen-activated protein kinases (MAPKs) pathway are important in inflammation. We recently found that the tanshinone IIA, a diterpene isolated from Salvia miltiorrhiza (S. miltiorrhiza), reduced the production of pro-inflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). However, little is known about the inhibitory mechanisms of tanshinone IIA on the production of pro-inflammatory mediators. To investigate the inhibitory mechanism, we determined the inhibitory effects of tanshinone IIA on the activation of NF-kappaB and IkappaB alpha phosphorylation, and also examined phosphorylation of NIK and IKK as well as the activation of MAPKs such as p38 MAPK (p38), extracellular signal-regulated kinases 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in RAW 264.7 cells stimulated with LPS. Tanshinone IIA inhibited NF-kappaB- DNA complex, NF-kappaB binding activity, and the phosphorylation of IkappaB alpha in a dose dependent manner. Tanshinone IIA also inhibited the translocation of NF-kappaB from cytosol to nucleus. Moreover, the phosphorylation of NIK and IKK as well as the phosphorylation of p38, ERK1/2, and JNK in the LPS-stimulated RAW 264.7 cells were suppressed by the tanshinone IIA in a dose dependent manner. These results suggest that tanshinone IIA may inhibit LPS-induced IkappaB alpha degradation and NF-kappaB activation via suppression of the NIK-IKK pathway as well as the MAPKs (p38, ERK1/2, and JNK) pathway in RAW 264.7 cells and these properties may provide a potential mechanism that explains the anti-inflammatory activity of tanshinone IIA.
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Authors | Seon Il Jang, Hyung Jin Kim, Young-Jun Kim, Seung-Il Jeong, Yong-Ouk You |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 542
Issue 1-3
Pg. 1-7
(Aug 07 2006)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 16797002
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Abietanes
- Lipopolysaccharides
- NF-kappa B
- Phenanthrenes
- tanshinone
- Protein Serine-Threonine Kinases
- I-kappa B Kinase
- JNK Mitogen-Activated Protein Kinases
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- NF-kappa B kinase
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Topics |
- Abietanes
- Animals
- Cell Line
- Dose-Response Relationship, Drug
- Enzyme Activation
(drug effects)
- I-kappa B Kinase
(metabolism)
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- Lipopolysaccharides
(pharmacology)
- Macrophages
(cytology, drug effects, metabolism)
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Mitogen-Activated Protein Kinases
(metabolism)
- Molecular Structure
- NF-kappa B
(metabolism)
- Phenanthrenes
(chemistry, pharmacology)
- Phosphorylation
(drug effects)
- Protein Serine-Threonine Kinases
(metabolism)
- Signal Transduction
(drug effects)
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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