Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer's amyloid-induced mitochondrial dysfunction

J Alzheimers Dis. 2011;26(3):507-21. doi: 10.3233/JAD-2011-101629.


Amyloid-β (Aβ)-induced mitochondrial dysfunction may play a role in the onset and progression of Alzheimer's disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Plant-derived flavonoids have shown promise in improving certain AD phenotypes, but the overall mechanism of action(s) through which flavonoids protect from AD is still unknown. To identify flavonoids and other natural products that may correct amyloid-induced mitochondrial dysfunction, 25 natural products were screened for their ability to restore altered mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, or ATP levels in neuroblastoma cells expressing mutant amyloid-β protein precursor (AβPP). Epigallocatechin-3-gallate (EGCG) and luteolin were identified as the top two mitochondrial restorative compounds from the in vitro screen. EGCG was further tested in vivo to determine its effects on brain mitochondrial function in an AβPP/PS-1 (presenilin 1) double mutant transgenic mouse model of AD. EGCG treatment restored mitochondrial respiratory rates, MMP, ROS production, and ATP levels by 50 to 85% in mitochondria isolated from the hippocampus, cortex, and striatum. The results of this study lend further credence to the notion that EGCG and other flavonoids, such as luteolin, are 'multipotent therapeutic agents' that not only reduce toxic levels of brain Aβ, but also hold the potential to protect neuronal mitochondrial function in AD.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / biosynthesis
  • Amyloid beta-Peptides / toxicity*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Blotting, Western
  • Brain / drug effects
  • Brain / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flavonoids / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Mice
  • Mice, Transgenic
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondrial Diseases / chemically induced*
  • Mitochondrial Diseases / prevention & control*
  • Oxygen Consumption / drug effects
  • Reactive Oxygen Species / metabolism


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Flavonoids
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • Catechin
  • epigallocatechin gallate