Dihydro-N-caffeoyltyramine down-regulates cyclooxygenase-2 expression by inhibiting the activities of C/EBP and AP-1 transcription factors

Dihydro-N-caffeoyltyramine (DHCT), a novel phenolic amide isolated from the root bark of Lycium clunence 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/EBP beta 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 DHCF. (C) 2009 Elsevier Ltd All rights reserved.