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Mar. Drugs 2009, 7(4), 589-599; doi:10.3390/md7040589
Article

Inhibitory Effect of N,N-Didesmethylgrossularine-1 on Inflammatory Cytokine Production in Lipopolysaccharide-Stimulated RAW 264.7 Cells

1,* , 2,†
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3
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1 Faculty of Pharmaceutical Sciences, Keio University/Minato-ku, Tokyo 105-8512, Japan 2 Department of Natural Products Chemistry, Tohoku Pharmaceutical University/Aoba-ku, Sendai 981-8558, Japan 3 Integrated Research Institute, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology/4259 Nagatsuda-cho, Midori-ku, Yokohama 226-8501, Japan 4 Faculty of Fisheries and Marine Science, Sam Ratulangi University/Kampus Bahu, Manado 95115, Indonesia On leave from the Division of Marine Life Science, Gyeongsang National University, Tongyeong, Kyungnam 650-160, Korea.
* Author to whom correspondence should be addressed.
Received: 13 October 2009 / Revised: 11 November 2009 / Accepted: 16 November 2009 / Published: 17 November 2009
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Abstract

N,N-Didesmethylgrossularine-1 (DDMG-1), a compound with a rare α-carboline structure, was isolated from an Indonesian ascidian Polycarpa aurata as responsible for the observed inhibitory activity against TNF-α production in lipopolysaccharide-stimulated murine macrophage-like RAW264.7 cells. DDMG-1 inhibited the mRNA level of mTNF-α, IκB-α degradation, and binding of NF-κB to the target DNA site in LPS-stimulated RAW 264.7 cells. Moreover, DDMG-1 had an inhibitory effect on the production of IL-8, which is produced in CD14+-THP-1 cells stimulated by LPS. DDMG-1 is thus a promising drug candidate lead compound for the treatment of chronic inflammatory diseases, such as rheumatoid arthritis.
Keywords: LPS; RAW 264.7 cells; NF-κB; TNF-α; N,N-didesmethylgrossularine-1; natural product LPS; RAW 264.7 cells; NF-κB; TNF-α; N,N-didesmethylgrossularine-1; natural product
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Oda, T.; Lee, J.-S.; Sato, Y.; Kabe, Y.; Sakamoto, S.; Handa, H.; Mangindaan, R.E.P.; Namikoshi, M. Inhibitory Effect of N,N-Didesmethylgrossularine-1 on Inflammatory Cytokine Production in Lipopolysaccharide-Stimulated RAW 264.7 Cells. Mar. Drugs 2009, 7, 589-599.

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