Inhibitory effect of 3-caffeoyl-4-dicaffeoylquinic acid from Salicornia herbacea against phorbol ester-induced cyclooxygenase-2 expression in macrophages

Salicornia herbacea (S. herbacea). an annual herb that grows in the salt marshes of the Korean peninsula, has been used as a folk medicine to treat a variety of diseases such as constipation, obesity, diabetes. and cancer. However, the effect of S. herbacea on inflammation is unclear. In the present study, we investigated the effects of a novel chlorogenic acid, 3-caffeoyl-4-dicaffeoylquinic acid (CDCQ), isolated from S. herbacea, on cyclooxygenase-2 (COX-2) expression in murine macrophage RAW 264.7 cells. Phorbol 12-myristate 13-acetate (PMA) induces COX-2 expression and production of prostaglandin E-2 (PGE(2)).PMA-incluced COX-2 protein, gene expression and PGE2 production were significantly inhibited by CDCQ in a dose-dependent manner. Transfection of hCOX-2, as well as of deletion and mutation promoter constructs, revealed that the CCAAT/enhancer-binding protein (C/EBP) and activator protein-1 (AP-1) predominantly contributed to the effects of CDCQ. In addition, electrophoretic mobility shift assays and transfection results showed that CDCQ directly inhibited PMA-induced C/EBP and AP-1 transcription and binding activity. CDCQ also remarkably reduced PMA-induced C/EBP beta and c-jun protein expression. Furthermore,CDCQ significantly inhibited PMA-induced activation of the mitogen-activated protein kinases (MAP kinases),JNK and p38. These findings demonstrate that CDCQ effectively attenuates COX-2 production, and enhance Our understanding of the anti-inflammatory properties ofCDCQ. (C) 2009 Elsevier Ireland Ltd. All rights reserved.