Basic & clinical pharmacology & toxicology, 2010-06, Vol.106 (6), p.454-460
2010
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- Autor(en) / Beteiligte
- Titel
- 2'-Methoxy-4'6'-Bis(Methoxymethoxy)Chalcone Inhibits Nitric Oxide Production in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages
- Ist Teil von
- Basic & clinical pharmacology & toxicology, 2010-06, Vol.106 (6), p.454-460
- Ort / Verlag
- Oxford: Blackwell
- Erscheinungsjahr
- 2010
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1742-7835eISSN: 1742-7843DOI: 10.1111/j.1742-7843.2009.00524.xTitel-ID: cdi_proquest_miscellaneous_744619038
- Format
- –
- Schlagworte
- Acetylcysteine, Animals, Anti-Inflammatory Agents - pharmacology, Antiinflammatory agents, Biological and medical sciences, c-Jun amino-terminal kinase, Cell Line, Chalcones - pharmacology, Enzymes, Gene Expression Regulation - drug effects, Glutathione, Glutathione - metabolism, Heme oxygenase (decyclizing), Heme Oxygenase-1 - metabolism, Inflammation, JNK Mitogen-Activated Protein Kinases - metabolism, Lipopolysaccharides, Macrophages, Macrophages - drug effects, Macrophages - metabolism, MAP kinase, Medical sciences, Metalloporphyrins - pharmacology, Mice, NF-B protein, NF-kappa B - metabolism, Nitric oxide, Nitric Oxide - metabolism, Nitric Oxide Synthase Type II - drug effects, Nitric Oxide Synthase Type II - genetics, Nitric-oxide synthase, p38 Mitogen-Activated Protein Kinases - metabolism, Pharmacology. Drug treatments, Protoporphyrins - pharmacology, tin protoporphyrin, Transcription factors