Neoline Improves Memory Impairment and Reduces Amyloid-β Level and Tau Phosphorylation Through AMPK Activation in the Mouse Alzheimer's Disease Model

J Alzheimers Dis. 2021;81(2):507-516. doi: 10.3233/JAD-201614.

Abstract

Background: Alzheimer's disease (AD) is the most general, chronic, and progressive neurodegenerative senile disorder characterized clinically by progressive cognitive deterioration and memory impairment. Neoline is effective against neuropathic pain models, but the effects of neoline against AD-like phenotypes have not been investigated.

Objective: We offer the investigation of the effects of neoline in AD.

Methods: In this study, a Tg-APPswe/PS1dE9 AD mouse model was treated orally with neoline at a concentration of 0.5 mg/kg or 0.1 mg/kg starting at 7.5 months and administered for three months, and its anti-AD effects were evaluated.

Results: Neoline improved memory and cognition impairments and reduced the number of amyloid-beta plaque and the amount of amyloid-β in the brain of AD mice. Furthermore, neoline reduced the anxiety behavior in the AD mouse model. The chronic administration of neoline also induced AMPK phosphorylation and decreased tau, amyloid-β, and BACE1 expression in the hippocampus. These findings indicate that chronic administration of neoline has therapeutic effects via AMPK activation, and BACE1 downregulation resulted in a decrease in the amyloid-β levels in the brain of Tg-APPswe/PS1dE9 AD mice.

Conclusion: Our results suggest that neoline is a therapeutic agent for the cure of neurodegenerative diseases like AD.

Keywords: AMPK; Alzheimer’s disease; BACE1; cognitive function; neoline; tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / drug effects*
  • AMP-Activated Protein Kinases / metabolism
  • Aconitine / analogs & derivatives*
  • Aconitine / pharmacology
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / drug effects
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Disease Models, Animal
  • Memory / drug effects
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism
  • Mice, Transgenic
  • tau Proteins / drug effects
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • neoline
  • tau Proteins
  • AMP-Activated Protein Kinases
  • Amyloid Precursor Protein Secretases
  • Aconitine