title: Naringenin attenuates the release of pro-inflammatory mediators from             lipopolysaccharide-stimulated BV2 microglia by inactivating nuclear factor-κB             and inhibiting mitogen-activated protein kinases.
abstract: Naringenin, one of the most abundant flavonoids in citrus fruits and grapefruits,             has been reported to exhibit anti-inflammatory and antitumor activities. However,             the cellular and molecular mechanisms underlying the naringenin anti-inflammatory             activity are poorly understood. In this study, we conducted an investigation of             the inhibitory effects of naringenin on the production of lipopolysaccharide (LPS)-induced             pro-inflammatory mediators in BV2 microglial cells. We found that pre-treatment             with naringenin prior to treatment with LPS significantly inhibited excessive             production of nitric oxide (NO) and prostaglandin E2 (PGE2) in a dose-dependent             manner. The inhibition was associated with downregulation of inducible nitric             oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Naringenin also             attenuated the production of pro-inflammatory cytokines and chemokines, including             interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant             protein-1 (MCP-1) by suppressing expression of mRNAs for these proteins. In addition,             the molecular mechanism underlying naringenin-mediated attenuation in BV2 cells             has a close relationship to suppressing translocation of the nuclear factor-κB             (NF-κB) p65 subunit into the nucleus and the phosphorylation of Akt and mitogen-activated             protein kinases (MAPKs). These findings suggest that naringenin may provide neuroprotection             through suppression of pro-inflammatory pathways in activated BV2 microglial cells.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental                     Medicine, Busan 614-052, 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: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D044950:Flavanones / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D044950:Flavanones; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C005273:naringenin; D015232:Dinoprostone