Inhibitory effect of N,N-didesmethylgrossularine-1 on inflammatory cytokine production in lipopolysaccharide-stimulated RAW 264.7 cells.
N,N-Didesmethylgrossularine-1 (DDMG-1), a compound with a rare alpha-carboline structure, was isolated from an Indonesian ascidian Polycarpa aurata as responsible for the observed inhibitory activity against TNF-alpha production in lipopolysaccharide-stimulated murine macrophage-like RAW264.7 cells. DDMG-1 inhibited the mRNA level of mTNF-alpha, IkappaB-alpha degradation, and binding of NF-kappaB 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.
Oda
Taiko
T
Faculty of Pharmaceutical Sciences, Keio University/Minato-ku, Tokyo, Japan. oda-ti@pha.keio.ac.jp
Lee
Jong-Soo
JS
Sato
Yuta
Y
Kabe
Yasuaki
Y
Sakamoto
Satoshi
S
Handa
Hiroshi
H
Mangindaan
Remy E P
RE
Namikoshi
Michio
M
D000818:Animals; D002243:Carbolines / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014561:Urochordata / Q000737:chemistry*
D002243:Carbolines; D016207:Cytokines; D020672:I-kappa B Proteins; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C550265:N,N-didesmethylgrossularine-1; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha