Evodiamine and rutaecarpine inhibit migration by LIGHT via suppression of NADPH oxidase activation

LIGHT acted as a new player in the atherogenesis. The dried, unripe fruit of Evodia Fructus (EF) has long been used as a traditional Chinese herbal medicine, and is currently widely used for the treatment of headache, abdominal pain, vomiting, colds and reduced blood circulation. Evodiamine and rutaecarpine are active components of EF. In this study, we investigated the inhibitory effect of evodiamine and rutaecarpine on LIGHT-induced migration in human monocytes. Evodiamine and rutaecarpine decreased the LIGHT-induced production of ROS, IL-8, monocyte chemoattractant protein-1 (MCP-1), TNF-alpha, and IL-6, as well as the expression of chemokine receptor (CCR) 1, CCR2 and ICAM-1 and the phosphorylation of the ERK 1/2 and p38 MAPK. Furthermore, NADPH oxidase assembly inhibitor, AEBSF, blocked LIGHT-induced migration and activation of CCR1, CCR2, ICAM-1, and MAPK such as ERK and p38 in a manner similar to evodiamine and rutaecarpine. These findings indicate that the inhibitory effects of evodiamine and rutaecarpine on LIGHT-induced migration and the activation of CCR1, CCR2, ICAM-1, ERK, and p38 MAPK occurs via decreased ROS production and NADPH oxidase activation. Taken together, these results indicate that evodiamine and rutaecarpine have the potential for use as an anti-atherosclerosis agent.