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
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; in revised form: 5 October 2013 / Accepted: 18 October 2013 / Published: 25 October 2013
(This article belongs to the Section Natural Products)
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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

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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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