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Inhibitory Effect of N,N-Didesmethylgrossularine-1 on Inflammatory Cytokine Production in Lipopolysaccharide-Stimulated RAW 264.7 Cells
Faculty of Pharmaceutical Sciences, Keio University/Minato-ku, Tokyo 105-8512, Japan
Department of Natural Products Chemistry, Tohoku Pharmaceutical University/Aoba-ku, Sendai 981-8558, Japan
Integrated Research Institute, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology/4259 Nagatsuda-cho, Midori-ku, Yokohama 226-8501, Japan
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; in revised form: 11 November 2009 / Accepted: 16 November 2009 / Published: 17 November 2009
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
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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.
Oda T, Lee J-S, Sato Y, Kabe Y, Sakamoto S, Handa H, Mangindaan REP, Namikoshi M. Inhibitory Effect of N,N-Didesmethylgrossularine-1 on Inflammatory Cytokine Production in Lipopolysaccharide-Stimulated RAW 264.7 Cells. Marine Drugs. 2009; 7(4):589-599.
Oda, Taiko; Lee, Jong-Soo; Sato, Yuta; Kabe, Yasuaki; Sakamoto, Satoshi; Handa, Hiroshi; Mangindaan, Remy E. P.; Namikoshi, Michio. 2009. "Inhibitory Effect of N,N-Didesmethylgrossularine-1 on Inflammatory Cytokine Production in Lipopolysaccharide-Stimulated RAW 264.7 Cells." Mar. Drugs 7, no. 4: 589-599.