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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
- Source :
- Molecules, Volume 19, Issue 11, Pages 18073-18089, Molecules, Vol 19, Iss 11, Pp 18073-18089 (2014)
- Publication Year :
- 2014
- Publisher :
- MDPI AG, 2014.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....6d91c4045eba5622e42a2ffe8de45f63