Kim So Ra, Kang So Young, Lee Ki Yong, Kim Seung Hyun, Markelonis George J, Oh Tae H, Kim Young Choong
College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul, 151-742, South Korea.
Brain Res Cogn Brain Res. 2003 Jul;17(2):454-61. doi: 10.1016/s0926-6410(03)00161-7.
We previously reported that phenylpropanoids isolated from the roots of Scrophularia buergeriana Miquel (Scrophulariaceae) protected cultured cortical neurons against glutamate-induced neurotoxicity [Kim and Kim, Phytochemistry, 54 (2000) 503-509; Kim et al., Br. J. Pharmacol. 135 (2002) 1281-1291]. In the present study, we examined the anti-amnestic activities of phenylpropanoids in mice with amnesia induced in vivo by scopolamine. Among the phenylpropanoids tested through passive avoidance tasks, buergeriside A1, buergeriside C1, E-p-methoxycinnamic acid (E-p-MCA) and E-isoferulic acid significantly improved the deficit of memory induced by scopolamine. This suggested that the alpha,beta-unsaturated carboxyl moiety and the para-methoxy group in phenylpropanoids (E-p-MCA) might be a crucial component in their cognition-enhancing activity. Indeed, E-p-MCA (0.01-2 mg/kg body weight, i.p.), given in pre- or post-treatment paradigms, significantly ameliorated scopolamine-induced amnesia as determined by passive avoidance tasks and prevented or aided in the recovery of memory to a level that was about 60% of control. In addition, E-p-MCA (0.1-1.0 mg/kg body weight, i.p.) significantly improved impairments of spatial learning and memory induced by scopolamine; the compound reduced deficits in both long- and short-term memories as measured by the Morris water maze test. We suggest, therefore, that E-p-MCA may ultimately hold significant therapeutic value in alleviating certain memory impairments observed in dementia.
我们之前报道过,从玄参科植物北玄参(Scrophularia buergeriana Miquel)根部分离得到的苯丙素类化合物可保护培养的皮层神经元免受谷氨酸诱导的神经毒性作用[Kim和Kim,《植物化学》,54 (2000) 503 - 509;Kim等人,《英国药理学期刊》,135 (2002) 1281 - 1291]。在本研究中,我们检测了苯丙素类化合物对东莨菪碱诱导的体内失忆小鼠的抗失忆活性。在通过被动回避任务测试的苯丙素类化合物中,伯格苷A1、伯格苷C1、E - 对甲氧基肉桂酸(E - p - MCA)和E - 异阿魏酸显著改善了东莨菪碱诱导的记忆缺陷。这表明苯丙素类化合物(E - p - MCA)中的α,β - 不饱和羧基部分和对甲氧基可能是其认知增强活性的关键成分。事实上,在治疗前或治疗后给予E - p - MCA(0.01 - 2 mg/kg体重,腹腔注射),通过被动回避任务测定,其显著改善了东莨菪碱诱导的失忆,并预防或帮助记忆恢复到约为对照水平的60%。此外,E - p - MCA(0.1 - 1.0 mg/kg体重,腹腔注射)显著改善了东莨菪碱诱导的空间学习和记忆损伤;该化合物减少了通过莫里斯水迷宫试验测量的长期和短期记忆缺陷。因此,我们认为E - p - MCA在缓解痴呆中观察到的某些记忆损伤方面可能最终具有重要的治疗价值。