Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
J Pharm Sci. 2011 Mar;100(3):1206-11. doi: 10.1002/jps.22354. Epub 2010 Oct 1.
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.
15-脂氧合酶（15-LOX）是形成氧化型低密度脂蛋白的关键酶之一，而氧化型低密度脂蛋白是动脉粥样硬化的主要致病因素。大麻的主要成分Δ（9）-四氢大麻酚（Δ（9）-THC）已被证明具有抑制动脉粥样硬化的作用。虽然Δ（9）-THC 似乎是预防动脉粥样硬化的理想选择，但目前尚不清楚Δ（9）-THC 是否可以抑制 15-LOX 同工酶。本研究发现，Δ（9）-THC 是 15-LOX 的直接抑制剂，其 IC50（50%抑制浓度）值为 2.42 μM。此外，Δ（9）-THC-11-羧酸，Δ（9）-THC 的主要非精神活性代谢物，但不是另一种 Δ（9）-THC 代谢物 11-OH-Δ（9）-THC（精神活性），被发现可以抑制 15-LOX。综上所述，Δ（9）-THC 可以通过直接抑制 15-LOX 来消除动脉粥样硬化，并且在这种情况下，Δ（9）-THC-11-羧酸被证明是 Δ（9）-THC 的“活性代谢物”。
