Epigallocatechin-3-Gallate Provides Protection Against Alzheimer's Disease-Induced Learning and Memory Impairments in Rats

Drug Des Devel Ther. 2021 May 13:15:2013-2024. doi: 10.2147/DDDT.S289473. eCollection 2021.

Abstract

Purpose: Recent evidence has highlighted the anti-inflammatory properties of the constituent of Green Tea Polyphenols (GTP), epigallocatechin-3-gallate (EGCG) which has been suggested to exert a neuroprotective effect on Alzheimer's disease (AD). The current study aimed to elucidate the effect of EGCG on memory function in rats with AD.

Methods: AD rat models were initially established through an injection with Aβ 25-35 solution, followed by gavage with EGCG at varying doses to determine the effect of EGCG on learning and cognitive deficits in AD. Morris water maze test was conducted to evaluate the spatial memory function of the rats. Immunohistochemistry and Western blot analysis were performed to identify Tau phosphorylation. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA and protein in rat hippocampus was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Acetylcholinesterase (AchE) activity, Aβ1-42 expression and Ach content were all detected using enzyme-linked immunosorbent assay (ELISA).

Results: EGCG intervention brought about a decrease in the escape latency period while increasing the time at the target quadrant among the AD rats. EGCG decreased the hyperphosphorylation of Tau in hippocampus. BACE1 expression and activity as well as the expression of Aβ1-42 were suppressed by EGCG. Moreover, EGCG promoted Ach content by diminishing the activity of AchE.

Conclusion: The current study demonstrates that EGCG may diminish the hyperphosphorylation of the Tau protein, downregulate BACE1 and Aβ1-42 expression to improve the antioxidant system and learning and memory function of rats with AD.

Keywords: ACh; AChE; Aβ1-42; BACE1; epigallocatechin-3-gallate; learning and memory function; tau hyperphosphorylation.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid beta-Peptides / genetics
  • Animals
  • Antioxidants / metabolism
  • Aspartic Acid Endopeptidases / genetics
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cognition Disorders / drug therapy
  • Cognition Disorders / physiopathology
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / physiopathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Spatial Memory / drug effects
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Catechin
  • epigallocatechin gallate
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, rat

Grants and funding

This study was supported by the Education Department of Jilin Province (No. JJKH20190060KJ).