Nobiletin from citrus fruit peel inhibits the DNA-binding activity of NF-κB 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 μM significantly suppressed NF-κB transcriptional activation, NO and PGE2 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 κB-α nor LPS-induced nuclear translocation of NF-κB. However, it interrupted the DNA-binding activity of activated NF-κB. As reactive oxygen species (ROS) are also known to regulate the activation of NF-κB, 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-κB DNA-binding activity and the suppression of ROS generation.