title: Phlorofucofuroeckol A suppresses expression of inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines via inhibition of nuclear factor-κB, c-Jun NH2-terminal kinases, and Akt in microglial cells.
abstract: Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the effects of phlorofucofuroeckol A isolated from Ecklonia stolonifera Okamura on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated microglia. Pre-treatment of phlorofucofuroeckol A attenuated the productions of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in LPS-stimulated microglia. Profoundly, phlorofucofuroeckol A treatment showed inactivation of nuclear factor-κB (NF-κB) by preventing the degradation of inhibitor κB-α and the nuclear translocation of p65 NF-κB subunit. Moreover, phlorofucofuroeckol A inhibited the activation of c-Jun NH2-terminal kinases (JNKs), p38 mitogen-activated protein kinase (MAPK), and Akt, but not that of extracellular signal-regulated kinase. These results indicate that phlorofucofuroeckol A inhibits the LPS-induced expression of inflammatory mediators through inactivation of NF-κB, JNKs, p38 MAPK, and Akt pathways. These findings suggest that phlorofucofuroeckol A can be considered as a nutraceutical candidate for the treatment of neuroinflammation in neurodegenerative diseases.
authors.affiliation: Molecular Nutrition Laboratory, Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737, South Korea.
authors.forename: A-Reum
authors.initials: AR
authors.lastname: Kim
authors.forename: Min-Sup
authors.initials: MS
authors.lastname: Lee
authors.forename: Ji-Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Utsuki
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: Hyeung-Rak
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004147:Dioxins / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D000459:Phaeophyceae; D010936:Plant Extracts / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D001572:Benzofurans; D016207:Cytokines; D004147:Dioxins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; C064093:phlorofucofuroeckol A; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone