title: Inhibitory effect of 3-caffeoyl-4-dicaffeoylquinic acid from Salicornia herbacea against phorbol ester-induced cyclooxygenase-2 expression in macrophages.
abstract: 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-induced COX-2 protein, gene expression and PGE(2) 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/EBPbeta 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 of CDCQ.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-Gu, Daejeon, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Hyo Kon
authors.initials: HK
authors.lastname: Chun
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Chung
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D045744:Cell Line, Tumor; D019663:Chenopodiaceae / Q000737:chemistry*; D002726:Chlorogenic Acid / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C547325:3-caffeoyl-4-dicaffeoylquinic acid; D022782:CCAAT-Enhancer-Binding Protein-beta; D010703:Phorbol Esters; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D002726:Chlorogenic Acid; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone