Rhamnetin Is a Potent Inhibitor of Extracellular Signal-regulated Kinase 1 and c-Jun N-Terminal Kinase 1

摘要

Rhamnetin is a flavonoid found in cloves and vegetables. Previously, we found that rhamnetin showed anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells, mediated by actions on mitogen-activated protein kinases pathways. Here, we investigated interactions between extracellular signal-regulated kinase 1 (ERK1) and rhamnetin. Based on docking study, we propose a binding model of rhamnetin and ERK1, where the 4-hydroxyl groups of the B-ring and the 5-hydroxyl group of the A-ring of rhamnetin play key roles. In a fluorescence quenching experiment, rhamnetin exhibited high binding affinity to ERK1. We found that rhamnetin has an IC50 value similar to that of the ERK1 inhibitor U0126 in ERK1 kinase assays, as well as to that of the JNK1 inhibitor SP600125 in JNK1 kinase assays. These results imply that rhamnetin may be a candidate inhibitor of ERK1 and JNK1, with potent anti-inflammatory activity.