L-3-n-butylphthalide improves cognitive impairment induced by intracerebroventricular infusion of amyloid-beta peptide in rats

Eur J Pharmacol. 2009 Oct 25;621(1-3):38-45. doi: 10.1016/j.ejphar.2009.08.036. Epub 2009 Sep 6.


Alzheimer's disease is the most common form of dementia. Amyloid-beta protein is considered as a key factor of pathogenesis of Alzheimer's disease. l-3-n-butylphthalide (L-NBP), an anti-cerebral ischemia drug, has been shown to have therapeutic effects in vascular dementia animal models. In the present study, we investigated the potential of L-NBP to protect against cognitive impairment, oxidative damage and neuropathological changes induced by intracerebroventricular infusion of amyloid-beta peptide in rats. Daily treatments of 10 and 30 mg/kg L-NBP significantly improved spatial learning deficits and attenuated working memory deficits in Morris water maze task. L-NBP partially reversed the reduction of glutathione peroxidase activities and decreased malondialdehyde levels in the cortex and hippocampus. Furthermore, L-NBP markedly inhibited amyloid-beta-induced neuronal apoptosis, possibly by blocking caspase-3 activation. In addition, L-NBP reduced activation of glycogen synthase kinase-3beta and tau protein phosphorylation. Our results demonstrate that L-NBP protects against amyloid-beta-induced neurodegeneration and cognitive decline in a rat model, suggesting that it may have potential as a therapy for Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Benzofurans / pharmacology*
  • Benzofurans / therapeutic use
  • Cerebral Ventricles*
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Infusion Pumps*
  • Learning / drug effects
  • Male
  • Memory / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Benzofurans
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • tau Proteins
  • 3-n-butylphthalide