Molecules 2013, 18(11), 13245-13259; doi:10.3390/molecules181113245
Article

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

1,2,†email, 1,3,†email, 1,2,4email, 5email, 6email, 1,2,4,* email and 1,2,4,* email
Received: 13 September 2013; in revised form: 5 October 2013 / Accepted: 18 October 2013 / Published: 25 October 2013
(This article belongs to the Section Metabolites)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: neoechinulin A; Eurotium rubrum; RAW264.7 macrophages; inflammation; NF-κB; MAPK
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MDPI and ACS Style

Kim, K.-S.; Cui, X.; Lee, D.-S.; Sohn, J.H.; Yim, J.H.; Kim, Y.-C.; Oh, H. 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 2013, 18, 13245-13259.

AMA Style

Kim K-S, Cui X, Lee D-S, Sohn JH, Yim JH, Kim Y-C, Oh H. 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. 2013; 18(11):13245-13259.

Chicago/Turabian Style

Kim, Kyoung-Su; Cui, Xiang; Lee, Dong-Sung; Sohn, Jae H.; Yim, Joung H.; Kim, Youn-Chul; Oh, Hyuncheol. 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, no. 11: 13245-13259.


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