title: Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264.7 cells.
abstract: Although fisetin, a natural flavonoid, was known to inhibit proliferation, carcinogenesis and inflammation, the underlying anti-inflammatory mechanism of fistein still remains unclear. Thus, in the present study, the anti-inflammatory mechanism of fisetin was investigated in association with mitogen-activated protein kinase (MAPK) and nuclear factor κ B (NF-κB) pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophages. We found that fisetin significantly reduced the nitrate oxide (NO) production and also inhibited the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) at protein and mRNA levels in LPS-stimulated cells. Consistently, fisetin significantly reduced the LPS-stimulated secretion of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor α (TNF-α). Furthermore, fisetin suppressed the activation of nuclear factor κ B (NF-κB) and the phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal regulated kinase (ERK) and p38 MAPK in LPS-treated RAW264.7 cells. Overall, our findings demonstrate that fisetin exerted anti-inflammatory activity via inactivation of JNK and NF-κB in LPS-stimulated macrophage cells.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Sun-Chae
authors.initials: SC
authors.lastname: Kim
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Kang
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Ko
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000276:immunology; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D044948:Flavonols; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; C017875:fisetin