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

Dong-Cheol Kim³  Hee-Suk Lee³  Wonmin Ko³  Dong-Sung Lee¹  Jae Hak Sohn⁴  Joung Han Yim²  Youn-Chul Kim³  Hyuncheol Oh³ 

[1] Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 400-712, Korea; E-Mail:;Korea Polar Research Institute, KORDI, 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Korea; E-Mail:;Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea; E-Mails:;College of Medical and Life Sciences, Silla University, Busan 617-736, Korea; E-Mail:

关键词: methylpenicinoline;    Penicillium sp.;    marine fungus;    anti-inflammation;    nuclear factor-kappa B (NF-κB);    mitogen-activated protein kinase (MAPK);   

DOI  :  10.3390/molecules191118073

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.