title: Anti-inflammatory effects of trans-1,3-diphenyl-2,3-epoxypropane-1-one mediated by suppression of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.
abstract: To assess the potential therapeutic properties of trans-1,3-diphenyl-2,3-epoxypropane-1-one (DPEP), its anti-inflammatory effects were investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) cells. DPEP induced dose-dependent reduction of the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitant reduction in the production of NO and prostaglandin E(2) (PGE(2)). Additionally, DPEP suppressed the production of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. We investigated the mechanism by which DPEP inhibits NO and PGE(2) by examining the level of nuclear factor-κB (NF-κB) activation within the mitogen-activated protein kinase (MAPK) pathway, which is an inflammation-induced signaling pathway in RAW 264.7 cells. DPEP inhibited LPS-induced phosphorylation of ERK, JNK, and p38. Furthermore, DPEP inhibited the LPS-induced phosphorylation of inhibitor κB (IκB)-α and NF-κB p50. Taken together, the results of this study demonstrate that DPEP inhibits LPS-stimulated inflammation by blocking the NF-κB and MAPK pathways in macrophages.
authors.affiliation: Marine Bio Research Team, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea.
authors.forename: Kil-Nam
authors.initials: KN
authors.lastname: Kim
authors.forename: Yeong-Jong
authors.initials: YJ
authors.lastname: Ko
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Kang
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Yang
authors.forename: Seong Woon
authors.initials: SW
authors.lastname: Roh
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oda
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Heo
authors.forename: Weon-Jong
authors.initials: WJ
authors.lastname: Yoon
authors.forename: Daekyung
authors.initials: D
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D004852:Epoxy Compounds; D051550:I-kappa B Kinase; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011407:Propane; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C582886:trans-1,3-diphenyl-2,3-epoxypropane-1-one; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse