Prodelphinidin B-4 3'-O-gallate, a tea polyphenol, is involved in the inhibition of COX-2 and iNOS via the downregulation of TAK1-NIF-κB 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 NOS at both mRNA and protein levels with the attendant decrease of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production. Molecular data revealed that PDG downregulated NF-kappa B signaling pathway. Electrophoretic mobility shift assay (EMSA) showed that PDG reduced the binding complex of NF-kappa B-DNA in the promoter of COX-2 and NOS. Immunochemical analysis revealed that PDG suppressed LPS-induced phosphorylation and degradation of I kappa B alpha, and subsequent nuclear translocation of p65. Consequently, PDG suppressed phosphorylation of I kappa B kinase alpha/beta (IKK alpha/beta) and TGF-beta-activated kinase (TAK1). Taken together, our data indicated that PDG is involved in the inhibition of COX-2 and NOS via the downregulation of TAK1-NF-kappa B pathway, revealing partial molecular basis for the anti -inflammatory properties of tea PDG. (C) 2007 Published by Elsevier Inc.