title: Δ9-tetrahydrocannabinol and its major metabolite Δ9-tetrahydrocannabinol-11-oic acid as 15-lipoxygenase inhibitors.
abstract: 15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein, a major causal factor for atherosclerosis. Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a major component of marijuana, has suggested to suppress atherosclerosis. Although Δ(9)-THC seems to be attractive for the prevention of atherosclerosis, there is no information about whether or not 15-LOX isoform can be inhibited by Δ(9)-THC. In the present study, Δ(9)-THC was found to be a direct inhibitor for 15-LOX with an IC(50) (50% inhibition concentration) value of 2.42 μM. Furthermore, Δ(9)-THC-11-oic acid, a major and nonpsychoactive metabolite of Δ(9) -THC, but not another Δ(9)-THC metabolite 11-OH-Δ(9)-THC (psychoactive), was revealed to inhibit 15-LOX. Taken together, it is suggested that Δ(9) -THC can abrogate atherosclerosis via direct inhibition of 15-LOX, and that Δ(9)-THC-11-oic acid is shown to be an "active metabolite" of Δ(9) -THC in this case.
authors.affiliation: Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
authors.forename: Rongrong
authors.initials: R
authors.lastname: Jiang
authors.forename: Hironori
authors.initials: H
authors.lastname: Aramaki
authors.forename: Masumi
authors.initials: M
authors.lastname: Imoto
authors.forename: Akihisa
authors.initials: A
authors.lastname: Toda
authors.forename: Reiko
authors.initials: R
authors.lastname: Eyanagi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Amamoto
authors.forename: Ikuo
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D050197:Atherosclerosis / Q000517:prevention & control*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism
chemical_list: D016859:Lipoxygenase Inhibitors; D043885:Receptor, Cannabinoid, CB2; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol; D001093:Arachidonate 15-Lipoxygenase