4.7 Article

Evodiamine improves congnitive abilities in SAMP8 and APPswe/PS1ΔE9 transgenic mouse models of Alzheimer's disease

Journal

ACTA PHARMACOLOGICA SINICA
Volume 32, Issue 3, Pages 295-302

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2010.230

Keywords

evodiamine; Alzheimer's disease; imaging; Morris water-maze test; SAMP8; APP(swe)/PS1(Delta E9); inflammation

Funding

  1. Ministry of Health Foundation [200802036]
  2. National Science and Technology Major Projects [2009ZX09501-026]

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Aim: To investigate the effect of evodiamine (a quinolone alkaloid from the fruit of Evodia rutaecarpa) on the progression of Alzheimer's disease in SAMP8 and APP(swe)/PS1(Delta E9) transgenic mouse models. Methods: The mice at age of 5 months were randomized into the model group, two evodiamine (50 mg.kg(-1).d(-1) and 100 mg.kg(-1).d(-1)) groups and an Aricept (2 mg.kg(-1).d(-1)) group. The littermates of no-transgenic mice and senescence accelerated mouse/resistance 1 mice (SAMR1) were used as controls. After 4 weeks of treatment, learning abilities and memory were assessed using Morris water-maze test, and glucose uptake by the brain was detected using positron emission tomography/computed tomography (PET/CT). Expression levels of IL-1 beta, IL-6, and TNF-alpha in brain tissues were detected using ELISA. Expression of COX-2 protein was determined using western blot. Results: In Morris water-maze test, evodiamine (100 mg.kg(-1).d(-1)) significantly alleviated the impairments of learning ability and memory. Evodiamine (100 mg.kg(-1).d(-1)) also reversed the inhibition of glucose uptake due to development of Alzheimer's disease traits in mice. Furthermore, the dose of evodiamine significantly decreased the expression of IL-1 beta, IL-6, TNF-alpha, and COX-2 that were involved in the inflammation due to Alzheimer's disease. Conclusion: The results indicate that evodiamine (100 mg.kg(-1).d(-1)) improves cognitive abilities in the transgenic models of Alzheimer's disease.

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