title: 7,8-Dihydroxyflavone attenuates the release of pro-inflammatory mediators and cytokines in lipopolysaccharide-stimulated BV2 microglial cells through the suppression of the NF-κB and MAPK signaling pathways.
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. However, the pharmacological mechanisms responsible for its anti-inflammatory activities in microglial cells have yet to be elucidated. In this study, we evaluated the anti-inflammatory effects of this compound on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. At non-toxic concentrations, 7,8-DHF attenuated the production of nitric oxide (NO) and prostaglandin E2 (PGE2), by inhibiting inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, respectively. Furthermore, the release and expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were inhibited by 7,8-DHF. In addition, 7,8-DHF suppressed nuclear factor-κB (NF-κB) translocation and its transcriptional activity by blocking IκB (IκB)-α degradation; in addition, it exerted suppressive effects on the phosphorylation of mitogen-activated protein kinases (MAPKs). These results indicate that 7,8-DHF possesses therapeutic potential against neurodegenerative diseases that involve microglial activation.
authors.affiliation: Department of Pharmacy, Busan National University, Busan 609-735, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Department of Life Science and Biotechnology, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Research Center for Anti-Aging Technology Development and Department of Biochemistry, Busan National University College of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Busan National University, Busan 609-735, Republic of Korea.
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.affiliation: Department of Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C485383:6,7-dihydroxyflavone; D016207:Cytokines; D047309:Flavones; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone