title: Green tea proanthocyanidins inhibit cyclooxygenase-2 expression in LPS-activated mouse macrophages: molecular mechanisms and structure-activity relationship.
abstract: The inhibitory effects of green tea proanthocyanidins on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) release were investigated in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. Prodelphinidin B2 3,3' di-O-gallate (PDGG) caused a dose-dependent inhibition of COX-2 at both mRNA and protein levels with the attendant release of PGE(2). Molecular evidence revealed that PDGG inhibited the degradation of Ikappa-B, nuclear translocation of p65 and CCAAT/enhancer-binding protein (C/EBP)delta, and phosphorylation of c-Jun, but not CRE-binding protein (CREB), which regulate COX-2 expression. Moreover, PDGG suppressed the activations of mitogen-activated protein kinase (MAPK) including c-Jun NH(2)-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase. The results demonstrated that PDGG suppressed COX-2 expression via blocking MAPK-mediated activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and C/EBPdelta. Furthermore, studies on structure-activity relationship using five kinds of proanthocyanidins revealed that the galloyl moiety of proanthocyanidins appeared important to their inhibitory actions. Thus, our findings provide the first molecular basis that green tea proanthocyanidins with the galloyl moiety might have anti-inflammatory properties through blocking MAPK-mediated COX-2 expression.
authors.affiliation: Department of Biochemical Science and Technology, Kagoshima University, Korimoto 1-21-24, Kagoshima City 890-0065, Japan. hou@ms.kagoshima-u.ac.jp
authors.forename: De-Xing
authors.initials: DX
authors.lastname: Hou
authors.forename: Satoko
authors.initials: S
authors.lastname: Masuzaki
authors.forename: Fumio
authors.initials: F
authors.lastname: Hashimoto
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanigawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujii
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D044945:Proanthocyanidins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000872:Anthocyanins; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D044945:Proanthocyanidins; C520449:prodelphinidin B2 3,3' di-O-gallate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone