Wang Chaoyun, Zhang Taiping, Ma Hongmei, Liu Juntian, Fu Fenghua, Liu Ke
Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Basic Clin Pharmacol Toxicol. 2007 Mar;100(3):190-5. doi: 10.1111/j.1742-7843.2007.00041.x.
Huperzine A is an anticholinesterase and cognitive enhancer, which is able to alleviate the symptoms of memory dysfunction in the mouse. The fast metabolization rate and narrow therapeutic spectrum makes it unfit for clinical use. Poly(lactic-co-glycolic acid) microsphere as delivery system effectively maintains the blood concentration of huperzine A by a slow-release effect over a long time. In the present article, we investigated the prolonged protective effect of microsphere-containing huperzine A on memory dysfunction induced by scopolamine. Spectrophotometric assay was used to determine the activity of acetylcholinesterase (AChE) and passive avoidance tests to evaluate memory performance. The results show that a bolus dose of microsphere-containing huperzine A (at a dose of 300 microg/kg or 600 microg/kg) administered intramuscularly can effectively maintain drug activity and significantly decrease the activity of AChE from day 3 to 14, the strongest effect seen on day 3 and 7. Accompanying the reduction of the activity of AChE, microsphere-containing huperzine A (300 microg/kg or 600 microg/kg) remarkably increased transfer latency time and no transfer response on the second trial through mitigating the memory impairments induced by scopolamine as compared to the scopolamine model group. Microsphere-containing huperzine A showed cognitive enhancing properties and anticholinesterase activity and may thus be a candidate for treatment of memory impairment.
石杉碱甲是一种抗胆碱酯酶和认知增强剂，能够缓解小鼠记忆功能障碍的症状。其快速的代谢率和狭窄的治疗谱使其不适合临床使用。聚乳酸-乙醇酸共聚物微球作为递送系统，通过缓释作用能在很长一段时间内有效维持石杉碱甲的血药浓度。在本文中，我们研究了含石杉碱甲微球对东莨菪碱诱导的记忆功能障碍的长期保护作用。采用分光光度法测定乙酰胆碱酯酶（AChE）的活性，并通过被动回避试验评估记忆性能。结果表明，肌肉注射大剂量含石杉碱甲微球（剂量为300μg/kg或600μg/kg）能有效维持药物活性，并在第3天至第14天显著降低AChE的活性，在第3天和第7天效果最强。伴随着AChE活性的降低，与东莨菪碱模型组相比，含石杉碱甲微球（300μg/kg或600μg/kg）通过减轻东莨菪碱诱导的记忆损伤，显著增加了第二次试验的转移潜伏期时间且无转移反应。含石杉碱甲微球具有认知增强特性和抗胆碱酯酶活性，因此可能是治疗记忆损伤的候选药物。
