Anti-inflammatory effect of neoechinulin a from the marine fungus Eurotium sp. SF-5989 through the suppression of NF-?B and p38 MAPK Pathways in lipopolysaccharide-stimulated RAW264.7 macrophages.

ABSTRACT: In the course of a bioassay-guided study of metabolites from the marine fungus Eurotium sp. SF-5989, two diketopiperazine type indole alkaloids, neoechinulins A and B, were isolated. In this study, we investigated the anti-inflammatory effects of neoechinulins A (1) and B (2) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Neoechinulin A (1) markedly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner ranging from 12.5 µM to 100 µM without affecting the cell viability. On the other hand, neoechinulin B (2) affected the cell viability at 25 µM although the compound displayed similar inhibitory effect of NO production to neoechinulin A (1) at lower doses. Furthermore, neoechinulin A (1) decreased the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?). We also confirmed that neoechinulin A (1) blocked the activation of nuclear factor-kappaB (NF-?B) in LPS-stimulated RAW264.7 macrophages by inhibiting the phosphorylation and degradation of inhibitor kappa B (I?B)-?. Moreover, neoechinulin A (1) decreased p38 mitogen-activated protein kinase (MAPK) phosphorylation. Therefore, these data showed that the anti-inflammatory effects of neoechinulin A (1) in LPS-stimulated RAW264.7 macrophages were due to the inhibition of the NF-?B and p38 MAPK pathways, suggesting that neoechinulin A (1) might be a potential therapeutic agent for the treatment of various inflammatory diseases.

SUBMITTER: Kim KS 

PROVIDER: S-EPMC6270177 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature