Acta Neuropharmacologica››2014,Vol. 4››Issue (5): 1-7.

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Study on the Effect and Mechanism of Early Intervention with Compound Danshen Tablet on Learning and Memory in APP/PS1 Transgenic Mice

Liu Min, Guo Hai-biao, Li Chu-yuan, Wang De-qin, Xu Jiang-ping, Qin Ren-an

  1. 1. Institute of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd, Guangzhou, 510515, China
    2. Department of Neuropharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China
  • Online:2014-10-26Published:2015-01-20
  • Contact:徐江平,男,博士生导师;研究方向:神经药理学;电话/传真:020-61648235; E-mail: jpx@smu.edu.cn 覃仁安,男,研究方向:神经药理学:E-mail: qinrenan@813zy.com
  • About author:刘旻,男,博士;研究方向:神经药理学;E-mail: liumin@813zy.com
  • Supported by:

    十二五重大新药创制 中药大品种复方丹参片系统研究及技术改造(No.2011ZX09201)

Abstract:Objective: To investigate effect of compound danshan tablet (CDST) on learning and memory in APP/PS1 transgenic mice and the underlying mechanism.Methods: APP/PS1 transgenic mice at the age of 4 months were orally administered with vehicle or CDST or donepezil for 8 weeks, then the behavioral performance of mice was tested using novel object recognition and step-down passive avoidance. Aβ40 and Aβ42 level in the hippocampus of wild-type mice and APP/PS1 mice were determined by ELISA assay. Real time PCR and Western blot were used to examine mRNA and protein expression of insulin degrading enzyme (IDE) and neprilysin (NEP) respectively.Results: Result of novel object recognition test showed that CDST (720 mg·kg-1) significantly increased the recognition index for the novel object in APP/PS1 mice. Step-down passive avoidance suggested that CDST (720,360mg·kg-1)-treated APP/PS1 mice significantly decreased the latency to stay on the platform. In addition, APP/PS1 mice treated by CDST (720 mg·kg-1) significantly increased retention on the platform. ELISA analysis showed that CDST (720,360mg·kg-1) decreased the level of Aβ40 and Aβ42 in the hippocampus of APP/PS1 mice. In Real time PCR, CDST (720mg·kg-1) statistically increased the mRNA expression of IDE and NEP in the hippocampus of APP/PS1 mice. Western blot analysis indicated that CDST (720mg·kg-1) significantly increased IDE expression in APP/PS1 mice.Conclusion: Improvement of learning and memory by CDST in APP/PS1 mice may be associated with the decreased of Aβ and increased of IDE expression.

Key words:Alzheimer&,rsquo,s disease (AD),APP/PS1 transgenic mice,Compound danshen tablet (CDST),&,beta,-amyloid (A&,beta,),Insulin degrading enzyme (IDE),Neprilysin (NEP)

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