title: 7,8-Dihydroxyflavone exhibits anti-inflammatory properties by downregulating             the NF-κB and MAPK signaling pathways in lipopolysaccharide-treated RAW264.7 cells.
abstract: 7,8-Dihydroxyflavone (7,8-DHF), a member of the flavonoid family, has received considerable attention as a selective tyrosine kinase receptor B agonist. Several studies have indicated that 7,8-DHF has neurotrophic and antioxidant activities. However, little is known about the cellular and molecular mechanisms underlying the anti-inflammatory activity of 7,8-DHF. Therefore, we investigated whether 7,8-DHF affects the expression of inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Our results indicated that 7,8-DHF significantly attenuated secretion of LPS-induced inflammatory mediators nitric oxide (NO), prostaglandin E₂ (PGE₂) and interleukin-1β (IL-1β) in RAW264.7 cells. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and IL-1β was decreased by pre-treatment with 7,8-DHF. Our results also showed that 7,8-DHF reduces LPS-induced nuclear factor-κB (NF-κB) activity via the suppression of the nuclear translocation of NF-κB p65 and the degradation of inhibitor κB (lκB). In addition, 7,8-DHF inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) such as extracellular-signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). These results suggest that the anti-inflammatory property of 7,8-DHF is related to the downregulation of iNOS, COX-2 and IL-1β, due to NF-κB inhibition as well as to the negative regulation of MAPK activation in RAW264.7 cells. Thus, 7,8-DHF may be a novel therapeutic agent for the prevention of various inflammatory diseases.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental                     Medicine, Busan, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Park
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Byung-Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects
chemical_list: C485383:6,7-dihydroxyflavone; D000893:Anti-Inflammatory Agents; D047309:Flavones; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone