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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,†
, 1,3,†
, 1,2,4
, 5
, 6
, 1,2,4,*  and 1,2,4,*
1 College of Pharmacy, Wonkwang University, Iksan 570-749, Korea 2 Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea 3 Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, 977 Gongyuan Road, Yanji 133002, Jilin, China 4 Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea 5 College of Medical and Life Sciences, Silla University, Busan 617-736, Korea 6 Korea Polar Research Institute, KORDI, 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Korea These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 13 September 2013 / Revised: 5 October 2013 / Accepted: 18 October 2013 / Published: 25 October 2013
(This article belongs to the Section Metabolites)
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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 neoechinulin A; Eurotium rubrum; RAW264.7 macrophages; inflammation; NF-κB; MAPK
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.

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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.

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