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)