Anti-inflammatory effect of methylpenicinoline from a marine isolate of Penicillium sp. (SF-5995): inhibition of NF-?B and MAPK pathways in lipopolysaccharide-induced RAW264.7 macrophages and BV2 microglia.

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 ?M to 80 ?M) without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1? (IL-1?). 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-?B) activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-? (I?B-?), thereby suppressing the nuclear translocation of NF-?B 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.

SUBMITTER: Kim DC 

PROVIDER: S-EPMC6271136 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature