Bajijiasu Ameliorates β-Amyloid-Triggered Endoplasmic Reticulum Stress and Related Pathologies in an Alzheimer's Disease Model

Cell Physiol Biochem. 2018;46(1):107-117. doi: 10.1159/000488414. Epub 2018 Mar 20.

Abstract

Background/aims: Alzheimer disease (AD) is a common neurodegenerative disease that is characterized by the deposition of beta-amyloid peptide and formation of intracellular neurofibrillary tangles. Due to the failure of various clinical trials of novel drugs for AD, effective drugs for AD treatment are urgently required.

Methods: In this study, we used the classic APP/PS1 mouse model to explore the neuroprotective effects of a new compound, bajijiasu, and the mechanisms involved. Behavioral tests and western blotting were performed to assess the beneficial effects of bajijiasu in APP/PS1 mice.

Results: Morris water maze and Y-maze test results showed that oral administration of bajijiasu (35 mg/kg/day and 70 mg/kg/day) improved learning and memory abilities in APP/PS1 mice. Bajijiasu reduced ROS and MDA levels in both the hippocampus and cortex. Moreover, western blotting results showed that bajijiasu protected neurons from apoptosis, elevated the expression levels of neurotrophic factors, and alleviated endoplasmic reticulum stress in both the hippocampus and cortex.

Conclusion: These results indicate that the mechanisms underlying the effects of bajijiasu on AD might be related to beta-amyloid-downstream pathologies, particularly endoplasmic reticulum stress.

Keywords: Alzheimer; Aβ; Bajijiasu; Disease; ER Stress.

MeSH terms

  • Administration, Oral
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Caspase 3 / metabolism
  • Cerebellar Cortex / drug effects
  • Cerebellar Cortex / metabolism
  • Disaccharides / chemistry
  • Disaccharides / pharmacology
  • Disaccharides / therapeutic use*
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress* / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Mice
  • Mice, Transgenic
  • Nerve Growth Factors / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Disaccharides
  • Nerve Growth Factors
  • Neuroprotective Agents
  • PSEN1 protein, human
  • Presenilin-1
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • fructofuranosyl-(2-2)-fructofuranosyl
  • Malondialdehyde
  • Caspase 3