Potent anti-inflammatory effects of denbinobin mediated by dual inhibition of expression of inducible no synthase and cyclooxygenase 2.
Shock
; 35(2): 191-7, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-20661183
ABSTRACT
Inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) have been suggested to play important roles in various inflammatory diseases. We explored the anti-inflammatory potential of a natural compound, denbinobin (5-hydroxy-3,7-dimethoxy-1,4-phenanthraquinone), by examining its effects on the expression and activity of iNOS and COX-2 in LPS-activated macrophages. Denbinobin markedly decreased the LPS (1 µg/mL)-induced increase in iNOS and COX-2 gene and protein expression, as well as levels of the downstream products NO and prostaglandin E2, in a concentration-dependent manner (0.3-3 µM). In clarifying the mechanisms involved, denbinobin was found not only to inhibit LPS-induced nuclear factor κB (NF-κB) activation, an effect highly correlated with its inhibitory effect on LPS-induced inhibitory κB kinase activation, inhibitory κB degradation, NF-κB phosphorylation, and binding of NF-κB to the κB motif of the iNOS and COX-2 promoters, but also suppressed phosphorylation of mitogen-activated protein kinases. Reporter gene assays and Western blotting revealed that denbinobin significantly suppressed NF-κB activation. Furthermore, denbinobin also downregulated the LPS-mediated CD14/toll-like receptor 4 complex level and TNF-α, IL-1ß, and IL-10 mRNA expression. Our results demonstrate that denbinobin exerts potent anti-inflammatory activity, suggesting that it might provide a new therapeutic approach to inflammatory diseases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenantrenos
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Regulación Enzimológica de la Expresión Génica
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Antraquinonas
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Ciclooxigenasa 2
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Óxido Nítrico Sintasa de Tipo II
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Macrófagos
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Antiinflamatorios
Límite:
Animals
Idioma:
En
Revista:
Shock
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Taiwán