Kang So Young, Lee Ki Yong, Koo Kyung Ah, Yoon Jeong Seon, Lim Song Won, Kim Young Choong, Sung Sang Hyun
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Life Sci. 2005 Feb 25;76(15):1691-705. doi: 10.1016/j.lfs.2004.07.029.
We assessed the effects of oral treatments of ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, on learning and memory deficit. The cognition-enhancing effect of ESP-102 was investigated in scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and Morris water maze performance tests. Acute oral treatment (single administration prior to scopolamine treatment) of mice with ESP-102 (doses in the range of 10 to 100 mg/kg body weight) significantly reduced scopolamine-induced memory deficits in the passive avoidance performance test. Another noteworthy result included the fact that prolonged oral daily treatments of mice with much lower amounts of ESP-102 (1 and 10 mg/kg body weight) for ten days reversed scopolamine-induced memory deficits. In the Morris water maze performance test, both acute and prolonged oral treatments with ESP-102 (single administration of 100 mg/kg body weight or prolonged daily administration of 1 and 10 mg/kg body weight for ten days, respectively, significantly ameliorated scopolamine-induced memory deficits as indicated by the formation of long-term and/or short-term spatial memory. In addition, we investigated the effects of ESP-102 on neurotoxicity induced by amyloid-beta peptide (Abeta25-35) or glutamate in primary cultured cortical neurons of rats. Pretreatment of cultures with ESP-102 (0.001, 0.01 and 0.1 mug/ml) significantly protected neurons from neurotoxicity induced by either glutamate or Abeta25-35. These results suggest that ESP-102 may have some protective characteristics against neuronal cell death and cognitive impairments often observed in Alzheimer's disease, stroke, ischemic injury and other neurodegenerative diseases.
我们评估了ESP - 102(一种由当归、三白草和五味子标准化组合提取物)口服治疗对学习和记忆缺陷的影响。通过东莨菪碱诱导(1毫克/千克体重,皮下注射)的失忆小鼠进行被动回避和莫里斯水迷宫性能测试,研究了ESP - 102的认知增强作用。用ESP - 102(剂量范围为10至100毫克/千克体重)对小鼠进行急性口服治疗(在东莨菪碱治疗前单次给药),在被动回避性能测试中显著降低了东莨菪碱诱导的记忆缺陷。另一个值得注意的结果是,用低得多的ESP - 102剂量(1和10毫克/千克体重)对小鼠进行为期十天的长期口服每日治疗,可逆转东莨菪碱诱导的记忆缺陷。在莫里斯水迷宫性能测试中,ESP - 102的急性和长期口服治疗(分别单次给予100毫克/千克体重或连续十天每日给予1和10毫克/千克体重),均显著改善了东莨菪碱诱导的记忆缺陷,这表现为长期和/或短期空间记忆的形成。此外,我们研究了ESP - 102对大鼠原代培养皮层神经元中由β淀粉样肽(Abeta25 - 35)或谷氨酸诱导的神经毒性的影响。用ESP - 102(0.001、0.01和0.1微克/毫升)对培养物进行预处理,可显著保护神经元免受谷氨酸或Abeta25 - 35诱导的神经毒性。这些结果表明,ESP - 102可能对阿尔茨海默病、中风、缺血性损伤和其他神经退行性疾病中常见的神经元细胞死亡和认知障碍具有一定的保护特性。