1. 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
- Author
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Hyuncheol Oh, Dong-Cheol Kim, Youn-Chul Kim, Joung Han Yim, Jae Hak Sohn, Hee-Suk Lee, Dong-Sung Lee, and Wonmin Ko
- 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 - 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.
- Published
- 2014