title: Oolong tea theasinensins attenuate cyclooxygenase-2 expression in lipopolysaccharide (LPS)-activated mouse macrophages: structure-activity relationship and molecular mechanisms.
abstract: Oolong tea theasinensins are a group of tea polyphenols different from green tea catechins and black tea theaflavins. The present study reports the inhibitory effects of oolong tea theasinensins on the expression of cyclooxygenase-2 (COX-2) and underlying molecular mechanisms in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. The structure-activity data revealed that the galloyl moiety of theasinensins played an important role in the inhibitory actions. Theasinensin A, a more potent inhibitor, caused a dose-dependent inhibition of mRNA, protein, and promoter activity of COX-2. An electrophoretic mobility shift assay (EMSA) revealed that theasinensin A reduced the complex of NF-κB- and AP-1-DNA in the promoter of COX-2. Signaling analysis demonstrated that theasinensin A attenuated IκB-α degradation, nuclear p65 accumulation, and c-Jun phosphorylation. Furthermore, theasinensin A suppressed the phosphorylation of MAPKs, IκB kinase α/β (IKKα/β), and TGF-β activated kinase (TAK1). These data demonstrated that the down-regulation of TAK1-mediated MAPKs and NF-κB signaling pathways might be involved in the inhibition of COX-2 expression by theasinensin A. These findings provide the first molecular basis for the anti-inflammatory properties of oolong tea theasinensins.
authors.affiliation: Department of Biochemical Science and Technology, United Graduate School of Agricultural SciencesKagoshima University, Korimoto 1-21-24, Kagoshima City, 890-0065 Japan. hou@chem.agri.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: Shunsuke
authors.initials: S
authors.lastname: Tanigawa
authors.forename: Fumio
authors.initials: F
authors.lastname: Hashimoto
authors.forename: Jihua
authors.initials: J
authors.lastname: Chen
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sogo
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujii
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D013329:Structure-Activity Relationship; D013662:Tea / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D008070:Lipopolysaccharides; D010636:Phenols; D010936:Plant Extracts; D013662:Tea; C481298:theasinensin A; D051546:Cyclooxygenase 2