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.
Heo
Sook-Kyoung
SK
Department of Prescriptionology, Cardiovascular Medical Research Center, University of Dongguk, Gyeongju City, Gyeongbuk, Republic of Korea. hsk927@yahoo.com
Yun
Hyun-Jeong
HJ
Yi
Hyo-Seung
HS
Noh
Eui-Kyu
EK
Park
Sun-Dong
SD
D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D026121:Indole Alkaloids / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D054390:Receptors, CCR2 / Q000187:drug effects / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D052999:Quinazolinones
D048049:Extracellular Signal-Regulated MAP Kinases; D026121:Indole Alkaloids; D018799:Intercellular Adhesion Molecule-1; D019255:NADPH Oxidases; D010750:Phosphoproteins; D010936:Plant Extracts; D017346:Protein Serine-Threonine Kinases; D011799:Quinazolines; D017382:Reactive Oxygen Species; D054390:Receptors, CCR2; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D048051:p38 Mitogen-Activated Protein Kinases; C515334:CCR2 protein, human; C505914:TNFSF14 protein, human; C085072:neutrophil cytosol factor 40K; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine; C071570:SNF1-related protein kinases