title: 2'-Methoxy-4'6'-bis(methoxymethoxy)chalcone inhibits nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages.
abstract: Chalcones have anti-inflammatory properties. Here, we synthesized 2'-methoxy-4'6'-bis(methoxymethoxy)chalcone (MBMC) and examined its anti-inflammatory effects. MBMC inhibited nitric oxide production and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. MBMC also blocked LPS-induced activation of nuclear factor kappaB (NF-kappaB), p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK). MBMC increased haem oxygenase 1 (HO-1) expression and nuclear accumulation of nuclear factor-erythroid 2-related factor 2 (Nrf2), an essential transcription factor for HO-1 induction. Treatment with tin protoporphyrin, a selective inhibitor of HO-1, reversed the inhibition of nitric oxide production by MBMC, suggesting that HO-1 induction mediates MBMC-mediated suppression of nitric oxide production. MBMC treatment rapidly and transiently decreased glutathione (GSH) levels, and treatment with GSH-Et (cell permeable form of GSH) or N-acetylcysteine (precursor of GSH) counteracted the HO-1 and Nrf2 expression elicited by MBMC, indicating that MBMC-induced HO-1 expression requires transient depletion of GSH. In summary, MBMC inhibits LPS-stimulated nitric oxide production via down-regulation of inflammatory pathways (NF-kappaB, p38 and JNK) and induction of the protective enzyme, HO-1.
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, Iksan, Jeonbuk, Korea.
authors.forename: Xing Yu
authors.initials: XY
authors.lastname: Jin
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.forename: Soon-Ai
authors.initials: SA
authors.lastname: Kim
authors.forename: Hak Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics; D011524:Protoporphyrins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C552404:2'-methoxy-4',6'-bis(methoxymethoxy)chalcone; D000893:Anti-Inflammatory Agents; D047188:Chalcones; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D016328:NF-kappa B; D011524:Protoporphyrins; D009569:Nitric Oxide; C032628:tin protoporphyrin IX; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione