Cannabidiol-2′,6′-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro

Shuso Takeda, Akari Hirayama, Shino Urata, Nobutaka Mano, Keiko Fukagawa, Midori Imamura, Ayumi Irii, Satomi Kitajima, Tomoko Masuyama, Mai Nomiyama, Sachiko Tatei, Saari Tomita, Taichi Kudo, Momoko Noguchi, Yasuhiro Yamaguchi, Yoshiko Okamoto, Toshiaki Amamoto, Yoshifumi Fukunishi, Kazuhito Watanabe, Curtis John OmiecinskiHironori Aramaki

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1252-1256
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume34
Issue number8
DOIs
StatePublished - Aug 2011

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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