Kim Dong Hyun, Yoon Byung Hoon, Kim Yong-Won, Lee Seungjoo, Shin Bum Young, Jung Ji Wook, Kim Hyoung Ja, Lee Yong Sup, Choi Jae Sue, Kim Sun Yeou, Lee Kyung-Tae, Ryu Jong Hoon
Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Korea.
J Pharmacol Sci. 2007 Sep;105(1):82-93. doi: 10.1254/jphs.fp0061565.
In the present study, we assessed the effect of the ethanolic extract of the seeds of Cassia obtusifolia (COE) on the learning and memory impairments induced by scopolamine or transient bilateral common carotid artery occlusion (2VO). In a study of the cholinergic dysfunction induced by scopolamine, single COE (25, 50, or 100 mg/kg, p.o.) administration significantly attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In the 2VO study, COE (50 mg/kg, p.o.) significantly reversed 2VO-induced cognitive impairments in mice by the passive avoidance and the Y-maze tasks (P<0.05). Moreover, COE (50 mg/kg, p.o.) also reduced escape-latency and prolonged swimming time in the target quadrant during a probe trial of the Morris water maze task (P<0.05). In an in vitro study, COE was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50) value: 81.6 microg/ml). Furthermore, COE also inhibited acetylcholinesterase activity in an ex vivo study. These results suggest that COE attenuates memory impairment induced by scopolamine or 2VO and that these effects are mediated by enhancing the cholinergic nervous system via acetylcholinesterase inhibition.
在本研究中,我们评估了决明子种子乙醇提取物(COE)对东莨菪碱或短暂双侧颈总动脉闭塞(2VO)诱导的学习和记忆损伤的影响。在一项关于东莨菪碱诱导的胆碱能功能障碍的研究中,单次口服COE(25、50或100mg/kg)显著减轻了东莨菪碱诱导的认知损伤,这通过被动回避和Y迷宫任务确定(P<0.05),并且还减少了莫里斯水迷宫任务中的逃避潜伏期(P<0.05)。在2VO研究中,COE(50mg/kg,口服)通过被动回避和Y迷宫任务显著逆转了2VO诱导的小鼠认知损伤(P<0.05)。此外,在莫里斯水迷宫任务的探索试验中,COE(50mg/kg,口服)还减少了逃避潜伏期并延长了在目标象限的游泳时间(P<0.05)。在一项体外研究中,发现COE以剂量依赖的方式抑制乙酰胆碱酯酶活性(IC(50)值:81.6μg/ml)。此外,在一项离体研究中COE也抑制了乙酰胆碱酯酶活性。这些结果表明,COE减轻了东莨菪碱或2VO诱导的记忆损伤,并且这些作用是通过抑制乙酰胆碱酯酶增强胆碱能神经系统来介导的。