Tetrahydroxy stilbene glucoside reduces the cognitive impairment and overexpression of amyloid precursor protein induced by aluminum exposure

Neurosci Bull. 2009 Dec;25(6):391-6. doi: 10.1007/s12264-009-0601-4.

Abstract

Objective: Excessive aluminum (Al) exposure impairs neurocognitive function in humans and animals. Epidemiologic studies have shown a potential linkage between chronic Al exposure and Alzheimer's disease. The present study aims to evaluate the effects of tetrahydroxy stilbene glucoside (TSG), the extract from herbal medicine Polygoni Multiflori, on cognitive impairment and the over-expression of hippocampal amyloid precursor protein (APP) induced by chronic exposure to Al in rats.

Methods: Rats were treated with 0.3% aluminum chloride (AlCl3) prepared in the drinking water for 90 d. AlCl3-treated animals were then randomly assigned to receive vehicle, TSG (4 g/kg), or Vitamin E (VE; 40 mg/kg) treatment for 5 months. VE served as a positive control. The effect of TSG was evaluated by passive avoidance task, and APP expression was evaluated by Western blotting.

Results: Following exposure to AlCl3 for 90 d, animals displayed a striking decrease (> 80%) in step-through latency in the passive avoidance task and a significant increase in the expression of APP in the hippocampus. Both TSG and VE significantly ameliorated the performance impairment in the passive avoidance task, and suppressed the over-expression of APP. Moreover, the effects of TSG, but not of VE, were in a time-dependent manner.

Conclusion: TSG may possess therapeutic effects against Alzheimer's disease.

目的: 过量的铝盐可损害人和动物的神经认知功能。 流行病学研究提示, 慢性铝中毒和阿尔茨海默病有潜在的联系。 本实验旨在评估中药何首乌提取物—二苯乙烯苷(TSG)对铝盐慢性中毒的大鼠认知功能的保护作用及海马部位β-淀粉样前体蛋白(APP)表达的影响。

方法: 以水配制0.3% 氯化铝, 连续喂养大鼠90 天。 随后铝盐暴露的大鼠随机分组, 采用溶媒, 进行TSG (4 g/kg)和VE (40 mg/kg)干预5 个月, 其中VE 作为对照药物。 结束后进行电刺激实验, 并用Western blot 法检测APP 的蛋白水平。

结果: 连续服用90 天AlCl3 后, 大鼠躲避电刺激能力显著下降, 并且海马部位APP 的表达显著上调。 经过TSD 和VE 干预后, 大鼠躲避电刺激能力得到显著改善, APP表达的上升也被显著抑制。 与VE相比, TSG的效果随时间延长而变得更为显著。

结论: TSG对阿尔茨海默病有一定的治疗作用。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Chloride
  • Aluminum Compounds / toxicity*
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Avoidance Learning / drug effects
  • Blotting, Western
  • Chlorides / toxicity*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / metabolism*
  • Glucosides / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Neuroprotective Agents / pharmacology*
  • Neuropsychological Tests
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Stilbenes / pharmacology*
  • Time Factors
  • Vitamin E / pharmacology
  • Vitamins / pharmacology

Substances

  • Aluminum Compounds
  • Amyloid beta-Protein Precursor
  • Chlorides
  • Glucosides
  • Neuroprotective Agents
  • Stilbenes
  • Vitamins
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • Vitamin E
  • Aluminum Chloride