Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells
Biomolecules & Therapeutics
;
: 258-263, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-59935
ABSTRACT
We demonstrate herein that silibinin, a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-alpha, and IL1beta. We also showed that silibinin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibitor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Sítios de Ligação
/
Modelos Moleculares
/
Expressão Gênica
/
Trifosfato de Adenosina
/
Western Blotting
/
Fator de Necrose Tumoral alfa
/
Silybum marianum
/
Sistema de Sinalização das MAP Quinases
/
Proteínas Quinases p38 Ativadas por Mitógeno
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Biomolecules & Therapeutics
Ano de publicação:
2013
Tipo de documento:
Artigo
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