論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |