RRC ID 1430
著者 Hou DX, Yanagita T, Uto T, Masuzaki S, Fujii M.
タイトル Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure-activity relationship and molecular mechanisms involved.
ジャーナル Biochem Pharmacol
Abstract The effects of anthocyanidins, the aglycon nucleuses of anthocyanins widely occurring in reddish fruits and vegetables, on the expression of cyclooxygenase-2 (COX-2) were investigated in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. Of five anthocyanidins, delphinidin and cyanidin inhibited LPS-induced COX-2 expression, but pelargonidin, peonidin and malvidin did not. The structure-activity relationship suggest that the ortho-dihydroxyphenyl structure of anthocyanidins on the B-ring appears to be related with the inhibitory actions. Delphinidin, the most potent inhibitor, caused a dose-dependent inhibition of COX-2 expression at both mRNA and protein levels. Western blotting analysis indicated that delphinidin inhibited the degradation of IkappaB-alpha, nuclear translocation of p65 and CCAAT/enhancer-binding protein (C/EBP)delta and phosphorylation of c-Jun, but not CRE-binding protein (CREB). Moreover, delphinidin suppressed the activations of mitogen-activated protein kinase (MAPK) including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase. MAPK inhibitors (U0126 for MEK1/2, SB203580 for p38 kinase and SP600125 for JNK) specifically blocked LPS-induced COX-2 expression. Thus, our results demonstrated that LPS-induced COX-2 expression by activating MAPK pathways and delphinidin suppressed COX-2 by blocking MAPK-mediated pathways with the attendant activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and C/EBPdelta. These findings provide the first molecular basis that anthocyanidins with ortho-dihydroxyphenyl structure may have anti-inflammatory properties through the inhibition of MAPK-mediated COX-2 expression.
巻・号 70(3)
ページ 417-25
公開日 2005-8-1
DOI 10.1016/j.bcp.2005.05.003
PII S0006-2952(05)00289-3
PMID 15963474
MeSH Animals Anthocyanins / chemistry* Anthocyanins / pharmacology Cell Line Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / chemistry* Cyclooxygenase Inhibitors / pharmacology Gene Expression Regulation, Enzymologic / drug effects Gene Expression Regulation, Enzymologic / physiology Lipopolysaccharides / antagonists & inhibitors Lipopolysaccharides / pharmacology* Macrophages / drug effects Macrophages / enzymology* Mice Mitogen-Activated Protein Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / biosynthesis Prostaglandin-Endoperoxide Synthases / biosynthesis Prostaglandin-Endoperoxide Synthases / genetics Prostaglandin-Endoperoxide Synthases / metabolism* Protein Kinase Inhibitors / pharmacology Structure-Activity Relationship Transcription, Genetic / drug effects
IF 4.96
引用数 149
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)