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
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- 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
- Kim, Kyoung-Su
Sohn, Jae Hak
Yim, Joung Han
- Biochemistry & Molecular Biology; Chemistry
- Neoechinulin A; Eurotium rubrum; RAW264.7 macrophages; Inflammation
- Issue Date
- Kim, Kyoung-Su, et al. 2013. "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". Molecules, 18: 13245-13259.
- 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
Molecules 2013, 18 13246
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.
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