Department of Pharmaceutical Sciences, MCPHS University, 179 Longwood Ave., Boston, MA, 02115, USA.
Mol Neurobiol. 2013 Oct;48(2):333-9. doi: 10.1007/s12035-013-8499-2. Epub 2013 Jul 14.
The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo. Previous studies have also demonstrated the activity of the pentane extract and its macamides, the most representative lipophilic constituents of Maca, in the endocannabinoid system as fatty acid amide hydrolase (FAAH) inhibitors. One of the most active macamides, N-3-methoxybenzyl-linoleamide, was studied to determine its mechanism of interaction with FAAH and whether it has inhibitory activity on mono-acyl glycerol lipase (MAGL), the second enzyme responsible for endocannabinoid degradation. Macamide concentrations from 1 to 100 μM were tested using FAAH and MAGL inhibitor assay methods and showed no effect on MAGL. Tests with other conditions were performed in order to characterize the inhibitory mechanism of FAAH inhibition. N-3-methoxybenzyl-linoleamide displayed significant time-dependent and dose-dependent FAAH inhibitory activity. The mechanism of inhibition was most likely irreversible or slowly reversible. These results suggest the potential application of macamides isolated from Maca as FAAH inhibitors, as they might act on the central nervous system to provide analgesic, anti-inflammatory, or neuroprotective effects, by modulating the release of neurotransmitters.
秘鲁植物 Lepidium meyenii（玛咖）已被证明具有体外和体内的神经保护活性。先前的研究还表明，戊烷提取物及其酰胺，即玛咖中最具代表性的亲脂性成分，在作为脂肪酸酰胺水解酶（FAAH）抑制剂的内源性大麻素系统中具有活性。最活跃的酰胺之一 N-3-甲氧基苄基-亚油酸酰胺，被研究以确定其与 FAAH 的相互作用机制，以及它是否对单酰基甘油脂肪酶（MAGL）具有抑制活性，MAGL 是负责内源性大麻素降解的第二种酶。使用 FAAH 和 MAGL 抑制剂测定方法测试了 1 至 100 μM 的酰胺浓度，结果表明对 MAGL 没有影响。为了表征 FAAH 抑制的抑制机制，进行了其他条件的测试。N-3-甲氧基苄基-亚油酸酰胺显示出显著的时间依赖性和剂量依赖性 FAAH 抑制活性。抑制机制很可能是不可逆的或缓慢可逆的。这些结果表明，玛咖中分离出的酰胺可能作为 FAAH 抑制剂的应用潜力，因为它们可能通过调节神经递质的释放，作用于中枢神经系统，提供镇痛、抗炎或神经保护作用。
