title: Anti-inflammatory effect of neoechinulin a from the marine fungus Eurotium sp. SF-5989 through the suppression of NF-кB 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-α (TNF-α) and interleukin-1β (IL-1β). We also confirmed that neoechinulin A (1) blocked the activation of nuclear factor-kappaB (NF-κB) in LPS-stimulated RAW264.7 macrophages by inhibiting the phosphorylation and degradation of inhibitor kappa B (IκB)-α. 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-κB and p38 MAPK pathways, suggesting that neoechinulin A (1) might be a potential therapeutic agent for the treatment of various inflammatory diseases.
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. yckim@wku.ac.kr.
authors.forename: Kyoung-Su
authors.initials: KS
authors.lastname: Kim
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Sohn
authors.forename: Joung Han
authors.initials: JH
authors.lastname: Yim
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D055325:Eurotium / Q000737:chemistry*; D026121:Indole Alkaloids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D026121:Indole Alkaloids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010879:Piperazines; C490266:neoechinulin A; D048051:p38 Mitogen-Activated Protein Kinases