dihydro-n-caffeoyltyramine and phorbolol-myristate-acetate

Dihydro-N-caffeoyltyramine (DHCT), a novel phenolic amide isolated from the root bark of Lycium chinense Miller, has potent antioxidative activity and anti-fungal effects. In the present study, we investigated the effects of DHCT on phorbol 12-myristate 13-acetate (PMA)-induced pro-inflammatory protein cyclooxygenase (COX-2) expression in macrophages. Treatment with DHCT suppressed PMA-mediated induction of COX-2 mRNA and protein. PMA-inducible production of PGE2 was inhibited by DHCT in a dose-dependent manner. Transient transfections and electrophoretic mobility shift assays indicated that the inhibitory effects of DHCT were mediated via CCAAT/enhancer-binding protein (C/EBP) and activator protein 1 (AP-1). DHCT reduced PMA-induced C/EBPbeta protein expression and c-jun/c-fos gene and protein expression. Furthermore, DHCT significantly inhibited PMA-induced activation of the mitogen activated protein (MAP) kinases (ERK and JNK). Thus, DHCT is an effective agent to attenuate COX-2 production mediated by the transcription factors C/EBP and AP-1, and these results enhance our understanding of the anti-inflammatory and anti-cancer properties by DHCT.

Topics: Animals; Antioxidants; Caffeic Acids; CCAAT-Enhancer-Binding Proteins; Cell Line; Cyclooxygenase 2; Dinoprostone; Down-Regulation; Enzyme Induction; Gene Expression Regulation, Enzymologic; Humans; Lycium; Macrophages; Plant Extracts; RNA, Messenger; Signal Transduction; Tetradecanoylphorbol Acetate; Transcription Factor AP-1; Transfection; Tyramine