Δ9-Tetrahydrocannabinol and Its Major Metabolite Δ9-Tetrahydrocannabinol-11-oic Acid as 15-Lipoxygenase Inhibitors
Δ9-Tetrahydrocannabinol and Its Major Metabolite Δ9-Tetrahydrocannabinol-11-oic Acid as 15-Lipoxygenase Inhibitors
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DOI：
10.1002/jps.22354
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发表时间：
2011-03-01
影响因子：
3.8
通讯作者：
Watanabe, Kazuhito
中科院分区：
文献类型：
--
作者：
Takeda, Shuso;Jiang, Rongrong;Watanabe, Kazuhito
15-脂氧合酶（15-LOX）是负责氧化低密度脂蛋白形成的关键酶之一，氧化低密度脂蛋白是动脉粥样硬化的主要病因。Delta（9）-四氢大麻酚（Delta（9）-THC）是大麻的主要成分，已被认为可以抑制动脉粥样硬化。尽管δ（9）-THC似乎对预防动脉粥样硬化有吸引力，但没有关于δ（9）-THC是否能抑制15-LOX同种型的信息。在本研究中，发现Delta（9）-THC是15-LOX的直接抑制剂，IC 50（50%抑制浓度）值为2.42 μ M。此外，发现Delta（9）-THC-11-oic acid（Delta（9）-THC的主要和非精神活性代谢物，而不是另一种Delta（9）-THC代谢物11-OH-Delta（9）-THC（精神活性））抑制15-LOX。综上所述，表明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-酸显示为Δ（9）-THC的“活性代谢物”。(C)2010 Wiley-Liss，Inc.和American Pharmacologist Association J Pharm Sci 100：1206-1211，2011
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. Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), a major component of marijuana, has suggested to suppress atherosclerosis. Although Delta(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 Delta(9)-THC. In the present study, Delta(9)-THC was found to be a direct inhibitor for 15-LOX with an IC50 (50% inhibition concentration) value of 2.42 mu M. Furthermore, Delta(9)-THC-11-oic acid, a major and nonpsychoactive metabolite of Delta(9)-THC, but not another Delta(9)-THC metabolite 11-OH-Delta(9)-THC (psychoactive), was revealed to inhibit 15-LOX. Taken together, it is suggested that Delta(9)-THC can abrogate atherosclerosis via direct inhibition of 15-LOX, and that Delta(9)-THC-11-oic acid is shown to be an "active metabolite" of Delta(9)-THC in this case. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1206-1211, 2011