Biological and Pharmaceutical Bulletin
Regular Articles
Cannabidiol-2′,6′-dimethyl Ether as an Effective Protector of 15-Lipoxygenase-Mediated Low-Density Lipoprotein Oxidation in Vitro
Shuso TakedaAkari HirayamaShino UrataNobutaka ManoKeiko FukagawaMidori ImamuraAyumi IriiSatomi KitajimaTomoko MasuyamaMai NomiyamaSachiko TateiSaari TomitaTaichi KudoMomoko NoguchiYasuhiro YamaguchiYoshiko OkamotoToshiaki AmamotoYoshifumi FukunishiKazuhito WatanabeCurtis John OmiecinskiHironori Aramaki
Author information
JOURNALS FREE ACCESS

Volume 34 (2011) Issue 8 Pages 1252-1256

Details
Download PDF (994K) Contact us
Abstract

15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein (ox-LDL), a major causal factor for atherosclerosis. Both enzymatic (15-LOX) and non-enzymatic (Cu2+) mechanisms have been proposed for the production of ox-LDL. We have recently reported that cannabidiol-2′,6′-dimethyl ether (CBDD) is a selective and potent inhibitor of 15-LOX-catalyzed linoleic acid oxygenation (Takeda et al., Drug Metab. Dispos., 37, 1733—1737 (2009)). In the LDL, linoleic acid is present as cholesteryl linoleate, the major fatty acid esterified to cholesterol, and is susceptible to oxidative modification by 15-LOX or Cu2+. In this investigation, we examined the efficacy of CBDD on i) 15-LOX-catalyzed oxygenation of cholesteryl linoleate, and ii) ox-LDL formation catalyzed by 15-LOX versus Cu2+-mediated non-enzymatic generation of this important mediator. The results obtained demonstrate that CBDD is a potent and selective inhibitor of ox-LDL formation generated by the 15-LOX pathway. These studies establish CBDD as both an important experimental tool for characterizing 15-LOX-mediated ox-LDL formation, and as a potentially useful therapeutic agent for treatment of atherosclerosis.

Information related to the author
© 2011 The Pharmaceutical Society of Japan
Previous article Next article

Recently visited articles
feedback
Top