Nobiletin from citrus fruit peel inhibits the DNA-binding activity of NF-kappaB and ROS production in LPS-activated RAW 264.7 cells.
Post-treatment with nobiletin (5,6,7,8,3',4'-hexamethoxy flavone), which was purified from the fruit peel of Citrus sunki Hort. ex Tanaka, at concentration 6-50 microM significantly suppressed NF-kappaB transcriptional activation, NO and PGE(2) production, and iNOS and COX-2 protein expression in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Nobiletin inhibited neither LPS-induced phosphorylation/degradation of inhibitory kappaB-alpha nor LPS-induced nuclear translocation of NF-kappaB. However, it interrupted the DNA-binding activity of activated NF-kappaB. As reactive oxygen species (ROS) are also known to regulate the activation of NF-kappaB, we tested the effect of nobiletin on LPS-induced ROS generation. Nobiletin significantly inhibited LPS-induced intracellular ROS production in RAW 264.7 cells. These results suggest that nobiletin may exert an anti-inflammatory effect through the interruption of NF-kappaB DNA-binding activity and the suppression of ROS generation.
Choi
Soo-Youn
SY
Department of Life Science, Cheju National University, 66 Jejudahakno, Jejusi, Jeju 690-756, Republic of Korea.
Hwang
Joon-Ho
JH
Ko
Hee-Chul
HC
Park
Ji-Gweon
JG
Kim
Se-Jae
SJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D002957:Citrus / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology*; D005638:Fruit; D008070:Lipopolysaccharides; D008264:Macrophages; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D047309:Flavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D004247:DNA; C008661:nobiletin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone