title: Phlorofucofuroeckol A inhibits the LPS-stimulated iNOS and COX-2 expressions in macrophages via inhibition of NF-κB, Akt, and p38 MAPK.
abstract: We have recently reported that phlorofucofuroeckol A isolated from the edible brown algae Ecklonia stolonifera showed potential antioxidative and anti-inflammatory properties in macrophage stimulated by LPS treatments. In this study, we further investigated the pharmacological characteristic of phlorofucofuroeckol A in regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 through regulatory and signaling pathways using LPS-treated RAW 264.7 cells. Treatment with 20 μM of phlorofucofuroeckol A significantly decreased levels of iNOS and COX-2 mRNA induced by LPS stimulation. As results, levels of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were significantly reduced by treatments of phlorofucofuroeckol A in LPS-stimulated RAW 264.7 cells. Phlorofucofuroeckol A inhibited promoter activities of inflammatory-mediators (iNOS and COX-2) and transcriptional factors (nuclear factor-κB, NF-κB, and AP-1) in LPS-treated RAW 264.7 cells. Moreover, phlorofucofuroeckol A inhibited activation of Akt and p38 MAPK in LPS-treated RAW 264.7 cells. These results indicate that the phlorofucofuroeckol A regulates iNOS and COX-2 expressions through the NF-κB-dependent transcriptional control associated with inhibition of multiple signaling proteins, suggesting potential candidates of phloroglucinol derivatives for treatments of inflammatory diseases.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, 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: Tai-Sun
authors.initials: TS
authors.lastname: Shin
authors.forename: Hong
authors.initials: H
authors.lastname: Hua
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: Jae-Sue
authors.initials: JS
authors.lastname: Choi
authors.forename: Dae-Seok
authors.initials: DS
authors.lastname: Byun
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Utsuki
authors.forename: Donald
authors.initials: D
authors.lastname: Ingram
authors.forename: Hyeung-Rak
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D004147:Dioxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C064093:phlorofucofuroeckol A; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases