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.
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.
Hou
De-Xing
DX
Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima City 890-0065, Japan. hou@ms.kagoshima-u.ac.jp
Luo
Dong
D
Tanigawa
Shunsuke
S
Hashimoto
Fumio
F
Uto
Takuhiro
T
Masuzaki
Satoko
S
Fujii
Makoto
M
Sakata
Yusuke
Y
D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D059808:Polyphenols; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D051996:Transcription Factor RelA; D000099151:MAP Kinase Kinase Kinase 7
D000872:Anthocyanins; D002352:Carrier Proteins; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D005419:Flavonoids; D051550:I-kappa B Kinase; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009363:Neoplasm Proteins; D052247:Nitric Oxide Synthase Type II; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D013662:Tea; D051996:Transcription Factor RelA; D000099151:MAP Kinase Kinase Kinase 7; C498144:Rela protein, mouse; C472180:prodelphinidin B-2 3'-O-gallate