title: Ecklonia cava ethanolic extracts inhibit lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV2 microglia via the MAP kinase and NF-kappaB pathways.
abstract: Ecklonia cava (EC) is a brown alga that has demonstrated radical scavenging, bactericidal, tyrosinase inhibitory, and protease inhibitory activities. However, the molecular mechanisms underlying its anti-inflammatory action remain unclear. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine BV2 microglia. Our results indicate that EC inhibits LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in a concentration-dependent manner and inhibits inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 in BV2 microglia without significant cytotoxicity. EC treatment significantly reduced nuclear factor-kappaB (NF-kappaB) translocation and DNA-binding in LPS-stimulated BV2 microglia. This effect was mediated through the inhibition of the degradation of the inhibitor kappaB and by inhibition of the mitogen-activated protein kinase (MAPK) phosphorylation, at least in part by inhibiting the generation of reactive oxygen species. Our data also indicate that EC extracts exert anti-inflammatory effects by suppressing proinflammatory cytokines. Collectively, these results suggest that EC suppresses the induction of cytokines by LPS, as well as iNOS and COX-2 expression, by blocking NF-kappaB and MAPK activation. These findings provide mechanistic insights into the anti-inflammatory and neuroprotective actions of EC in BV2 microglia.
authors.affiliation: Department of Marine Life Science, Marine Life Research Center, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Ahn
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Yea
authors.forename: Inhak
authors.initials: I
authors.lastname: Choi
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.forename: Soo-Woong
authors.initials: SW
authors.lastname: Lee
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000459:Phaeophyceae / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone