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 |
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Authors: | Hou De-Xing Luo Dong Tanigawa Shunsuke Hashimoto Fumio Uto Takuhiro Masuzaki Satoko Fujii Makoto Sakata Yusuke |
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Affiliation: | 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 |
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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. |
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Keywords: | COX-2, cyclooxygenase-2 EMSA, electrophoretic mobility shift assay IKK, IkappaB kinase iNOS, inducible nitric oxide synthase LPS, lipopolysaccharide NF-κB, nuclear factor kappaB NO, nitric oxide PDG, prodelphinidin B-4 3′-O-gallate PGE2, prostaglandin E2 TAK1, TGF-β-activated kinase TLR4, toll-like receptor 4 |
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