Anti-Inflammatory Effect of Neoechinulin A from the Marine Fungus Eurotium sp SF-5989 through the Suppression of NF-kappa B and p38 MAPK Pathways in Lipopolysaccharide-Stimulated RAW264.7 Macrophages

作者：Kim Kyoung Su; Cui Xiang; Lee Dong Sung; Sohn Jae Hak; Yim Joung Han; Kim Youn Chul^*; Oh Hyuncheol

来源：Molecules, 2013, 18(11): 13245-13259.

DOI：10.3390/molecules181113245

• neoechinulin A
• Eurotium rubrum
• RAW264.7 macrophages
• inflammation
• NF-kappa B
• MAPK

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 E-2 (PGE(2)) and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner ranging from 12.5 mu M to 100 mu M without affecting the cell viability. On the other hand, neoechinulin B (2) affected the cell viability at 25 mu M 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-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). We also confirmed that neoechinulin A (1) blocked the activation of nuclear factor-kappaB (NF-kappa B) in LPS-stimulated RAW264.7 macrophages by inhibiting the phosphorylation and degradation of inhibitor kappa B (I kappa B)-alpha. 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-kappa B and p38 MAPK pathways, suggesting that neoechinulin A (1) might be a potential therapeutic agent for the treatment of various inflammatory diseases.

• 出版日期2013-11
• 单位延边大学; 中国极地研究中心