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Molecules 2014, 19(11), 18073-18089; doi:10.3390/molecules191118073

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

1
Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea
2
Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 400-712, Korea
3
College of Medical and Life Sciences, Silla University, Busan 617-736, Korea
4
Korea Polar Research Institute, KORDI, 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Korea
*
Authors to whom correspondence should be addressed.
Received: 25 September 2014 / Revised: 28 October 2014 / Accepted: 28 October 2014 / Published: 5 November 2014
(This article belongs to the Collection Bioactive Compounds)
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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. View Full-Text
Keywords: methylpenicinoline; Penicillium sp.; marine fungus; anti-inflammation; nuclear factor-kappa B (NF-κB); mitogen-activated protein kinase (MAPK) methylpenicinoline; Penicillium sp.; marine fungus; anti-inflammation; nuclear factor-kappa B (NF-κB); mitogen-activated protein kinase (MAPK)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kim, D.-C.; Lee, H.-S.; Ko, W.; Lee, D.-S.; Sohn, J.H.; Yim, J.H.; Kim, Y.-C.; Oh, H. 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. Molecules 2014, 19, 18073-18089.

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