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Anti-resorptive saurolactam exhibits in vitro anti-inflammatory activity via ERK-NF-kappaB signaling pathway.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2010 Mar; Vol. 10 (3), pp. 298-303. Date of Electronic Publication: 2009 Dec 03. - Publication Year :
- 2010
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Abstract
- Natural products and their derivatives have historically been an invaluable a source of therapeutic agents. In this report, we demonstrated the anti-inflammatory activity of saurolactam, a compound isolated from the aerial portions of the Chinese lizard, Saururus chinensis. In RAW264.7 macrophage cells, saurolactam significantly inhibited the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 and, consequently, inhibited the release of NO and prostaglandin E2. Moreover, real-time PCR and multiplex cytokine assays showed that saurolactam (10 microM) significantly inhibited the LPS-induced mRNA and protein expression levels of pro-inflammatory genes, including interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha. Finally, western blot analysis showed that saurolactam dose-dependently inhibited LPS-induced extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase activation and nuclear factor (NF)-kappaB translocation into the nucleus. The inhibitory activity of saurolactam on the activation of NF-kappaB was confirmed by a NF-kappaB luciferase reporter gene assay. In conclusion, we propose that the in vitro anti-inflammatory activity of saurolactam is produced by blocking ERK/MAP kinase and NF-kappaB activation.<br /> (Copyright 2009 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Blotting, Western
Cell Line
Cell Survival drug effects
Cyclooxygenase 2 Inhibitors pharmacology
Cytokines analysis
Cytokines biosynthesis
Dinoprostone metabolism
Genes, Reporter genetics
Inflammation Mediators metabolism
Lipopolysaccharides pharmacology
Luciferases genetics
Macrophages drug effects
Mice
Nitric Oxide metabolism
Nitric Oxide Synthase Type II biosynthesis
RNA, Messenger biosynthesis
Saururaceae chemistry
Signal Transduction physiology
Anti-Inflammatory Agents, Non-Steroidal
Extracellular Signal-Regulated MAP Kinases physiology
Isoindoles pharmacology
NF-kappa B physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19962455
- Full Text :
- https://doi.org/10.1016/j.intimp.2009.11.014