Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995): Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia
| Autor: | Hyuncheol Oh, Dong-Cheol Kim, Youn-Chul Kim, Joung Han Yim, Jae Hak Sohn, Hee-Suk Lee, Dong-Sung Lee, Wonmin Ko |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
MAPK/ERK pathway Aquatic Organisms Lipopolysaccharide MAP Kinase Signaling System Penicillium sp medicine.medical_treatment Interleukin-1beta Anti-Inflammatory Agents Nitric Oxide Synthase Type II Pharmaceutical Science Biology Article Dinoprostone Cell Line Analytical Chemistry Nitric oxide lcsh:QD241-441 Mice chemistry.chemical_compound lcsh:Organic chemistry Drug Discovery medicine Animals nuclear factor-kappa B (NF-κB) mitogen-activated protein kinase (MAPK) Viability assay Physical and Theoretical Chemistry Prostaglandin E2 marine fungus Protein kinase A Macrophages Organic Chemistry NF-kappa B Penicillium NF-κB Molecular biology anti-inflammation Cytokine Biochemistry chemistry Cyclooxygenase 2 Chemistry (miscellaneous) Molecular Medicine Microglia methylpenicinoline medicine.drug |
| Zdroj: | Molecules Volume 19 Issue 11 Pages 18073-18089 Molecules, Vol 19, Iss 11, Pp 18073-18089 (2014) |
| ISSN: | 1420-3049 |
| Popis: | In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS) in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2) production by suppressing cyclooxygenase-2 (COX-2) expression in a concentration-dependent manner (from 10 μM to 80 μM) without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β). In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB) activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α), thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK) pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases. |
| Databáze: | OpenAIRE |
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