Ko Yong-Hyun, Shim Kyu-Yeon, Lee Seok-Yong, Jang Choon-Gon
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Biomol Ther (Seoul). 2018 Sep 1;26(5):432-438. doi: 10.4062/biomolther.2017.146.
Worldwide, caffeine is among the most commonly used stimulatory substances. Unfortunately, significant caffeine consumption is associated with several adverse effects, ranging from sleep disturbances (including insomnia) to cardiovascular problems. This study investigates whether treatment with the aqueous extract (ERAE) from berries and its major molecular component, evodiamine, can reduce the adverse caffeine-induced sleep-related and excitation effects. We combined measurements from the pentobarbital-induced sleep test, the open field test, and the locomotor activity test in mice that had been dosed with caffeine. We found that ERAE and evodiamine administration reduced the degree of caffeine-induced sleep disruption during the sleep test. Additionally, we found that evodiamine significantly inhibits caffeine-induced excitation during the open field test, as well as decreasing hyperlocomotion in the locomotor activity test. Additional experiments showed that caffeine administration decreased the expression of γ-aminobutyric acid (GABA) receptor subunits in the mouse hypothalamus. However, evodiamine treatment significantly reversed this expression reduction. Taken together, our results demonstrate that ERAE and its major compound, evodiamine, provide an excellent candidate for the treatment or prevention of caffeine-induced sleep disturbances and excitatory states, and that the mechanism of these beneficial effects acts, at least in part, through the GABA-ergic system.
在全球范围内，咖啡因是最常用的刺激性物质之一。不幸的是，大量摄入咖啡因会带来多种不良影响，从睡眠障碍（包括失眠）到心血管问题。本研究调查了浆果水提取物（ERAE）及其主要分子成分吴茱萸碱能否减轻咖啡因引起的与睡眠相关的不良影响和兴奋作用。我们结合了对服用咖啡因的小鼠进行的戊巴比妥诱导睡眠试验、旷场试验和自发活动试验的测量结果。我们发现，给予ERAE和吴茱萸碱可减轻睡眠试验中咖啡因引起的睡眠中断程度。此外，我们发现吴茱萸碱在旷场试验中显著抑制咖啡因引起的兴奋，并在自发活动试验中减少过度活动。额外的实验表明，给予咖啡因会降低小鼠下丘脑γ-氨基丁酸（GABA）受体亚基的表达。然而，吴茱萸碱治疗可显著逆转这种表达降低。综上所述，我们的结果表明，ERAE及其主要化合物吴茱萸碱是治疗或预防咖啡因引起的睡眠障碍和兴奋状态的极佳候选物，并且这些有益作用的机制至少部分通过GABA能系统起作用。
