Department of Functional and Analytical Food Sciences, Niigata University of Pharmacy & Applied Life Sciences, Niigata City, Japan.
J Med Food. 2011 Jun;14(6):601-9. doi: 10.1089/jmf.2010.1362. Epub 2011 May 9.
The aim of this study was to examine the effect of Shengmai-san (SMS) on learning and memory impairment induced by scopolamine (1 mg/kg, i.p.) in mice. The passive avoidance task (PAT) and Morris water maze (MWM) test served as the behavioral models for testing memory. To elucidate the mechanism of its cognitive-enhancing activity, the effects of SMS (2, 4, or 8 g/kg) on activities of acetylcholinesterase (AChE) and antioxidant enzymes and levels of acetylcholine (ACh) and nitrite were evaluated in brain homogenate. Tacrine (THA) (10 mg/kg, p.o.) was used as a reference drug. SMS (4 or 8 g/kg) significantly prevented scopolamine-induced impairments as measured by the PAT and MWM (probe trial session). SMS (4 or 8 g/kg) also significantly reduced the oxidative-nitrative stress, as evidenced by decreased malondialdehyde and nitrite levels and by its prevention of decreases in glutathione and superoxide dismutase levels. The activity of AChE was decreased in scopolamine-treated mice but was inhibited significantly by SMS treatment (4 or 8 g/kg) in both salt- and detergent-soluble fractions of brain homogenates. Further SMS treatment (4 or 8 g/kg) significantly increased the ACh levels in the brain homogenate to a level similar to that observed in THA treatment. Thus, the significant cognitive enhancement observed after 7 days of administration of SMS is closely related to the strong antioxidant properties of SMS in addition to its inhibition of brain AChE activity. These findings stress the critical impact of SMS on higher brain functions such as learning and memory.
本研究旨在考察生脉散（SMS）对东莨菪碱（1mg/kg，ip）诱导的小鼠学习记忆障碍的影响。被动回避任务（PAT）和 Morris 水迷宫（MWM）测试分别作为测试记忆的行为模型。为了阐明其认知增强活性的机制，评估了 SMS（2、4 或 8g/kg）对脑匀浆中乙酰胆碱酯酶（AChE）和抗氧化酶活性以及乙酰胆碱（ACh）和亚硝酸盐水平的影响。他克林（THA）（10mg/kg，po）用作参考药物。SMS（4 或 8g/kg）可显著预防 PAT 和 MWM（探针试验）中由东莨菪碱引起的损伤。SMS（4 或 8g/kg）还可显著降低氧化-硝化应激，表现为丙二醛和亚硝酸盐水平降低，谷胱甘肽和超氧化物歧化酶水平降低得到预防。脑匀浆中 AChE 的活性在东莨菪碱处理的小鼠中降低，但在 SMS 处理（4 或 8g/kg）时被显著抑制，无论是在盐溶性还是在去污剂溶性脑匀浆部分。进一步的 SMS 处理（4 或 8g/kg）可使脑匀浆中的 ACh 水平显著升高，达到与 THA 处理相似的水平。因此，在 7 天给药后观察到的显著认知增强与 SMS 的强抗氧化特性密切相关，除了抑制脑 AChE 活性外。这些发现强调了 SMS 对学习和记忆等高级脑功能的重要影响。
