RRC ID |
3864
|
著者 |
Hou DX, Luo D, Tanigawa S, Hashimoto F, Uto T, Masuzaki S, Fujii M, Sakata Y.
|
タイトル |
Prodelphinidin B-4 3'-O-gallate, a tea polyphenol, is involved in the inhibition of COX-2 and iNOS via the downregulation of TAK1-NF-kappaB pathway.
|
ジャーナル |
Biochem Pharmacol
|
Abstract |
Much is known about the bioactive properties of green tea flavan-3-ol. However, very little work has been done to determine the properties of proanthocyanidins, another kind of polyphenols in green tea. In this study, we have investigated the anti-inflammatory effect of tea prodelphinidin B-4 3'-O-gallate (PDG) by demonstrating the inhibitory effects on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. PDG caused a dose-dependent inhibition of COX-2 and iNOS at both mRNA and protein levels with the attendant decrease of prostaglandin E2 (PGE2) and nitric oxide (NO) production. Molecular data revealed that PDG downregulated NF-kappaB signaling pathway. Electrophoretic mobility shift assay (EMSA) showed that PDG reduced the binding complex of NF-kappaB-DNA in the promoter of COX-2 and iNOS. Immunochemical analysis revealed that PDG suppressed LPS-induced phosphorylation and degradation of IkappaBalpha, and subsequent nuclear translocation of p65. Consequently, PDG suppressed phosphorylation of IkappaB kinase alpha/beta (IKKalpha/beta) and TGF-beta-activated kinase (TAK1). Taken together, our data indicated that PDG is involved in the inhibition of COX-2 and iNOS via the downregulation of TAK1-NF-kappaB pathway, revealing partial molecular basis for the anti-inflammatory properties of tea PDG.
|
巻・号 |
74(5)
|
ページ |
742-51
|
公開日 |
2007-9-1
|
DOI |
10.1016/j.bcp.2007.06.006
|
PII |
S0006-2952(07)00367-X
|
PMID |
17658484
|
MeSH |
Animals
Anthocyanins / chemistry
Anthocyanins / pharmacology*
Carrier Proteins / metabolism
Cell Line
Cyclooxygenase 2 / metabolism*
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology*
Down-Regulation / drug effects*
Flavonoids / chemistry
Flavonoids / pharmacology
I-kappa B Kinase / metabolism
MAP Kinase Kinase Kinases / metabolism*
Macrophages / drug effects
Macrophages / metabolism
Mice
Molecular Structure
NF-kappa B / metabolism*
Neoplasm Proteins / metabolism
Nitric Oxide Synthase Type II / antagonists & inhibitors*
Phenols / chemistry
Phenols / pharmacology
Polyphenols
Protein Transport
RNA, Messenger / metabolism
Tea / chemistry*
Transcription Factor RelA
|
IF |
4.96
|
引用数 |
45
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |