Inhibition of Aβ aggregates in Alzheimer’s disease by epigallocatechin and epicatechin-3-gallate from green tea

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive accumulation of senile plaques, which are primarily composed of misfolded amyloid β-peptide (Aβ). Aβ aggregates are believed to be a key factor in the pathogenesis of AD, affecting the nervous system in human body. The therapeutic potential of tea-derived polyphenolic compounds, (–)-epigallocatechin (EGC) and (–)-epicatechin-3-gallate (ECG), for AD was investigated by assessing their effects on the Cu2+/Zn2+-induced or self-assembled Aβ40 aggregation using thioflavine T fluorescent spectrometry, inductively coupled plasma mass spectrometry, UV–Vis spectroscopy, transmission electron microscope, silver staining, immunohistochemistry, and immunofluorescence assays. EGC and ECG mildly bind to Cu2+ and Zn2+, and diminish the Cu2+- or Zn2+-induced or self-assembled Aβ aggregates; they also modulate the Cu2+/Zn2+-Aβ40 induced neurotoxicity on mouse neuroblastoma Neuro-2a cells by reducing the production of ROS. Metal chelating, hydrogen bonding or Van Der Waals force may drive the interaction between the polyphenolic compounds and Aβ. The results demonstrate that green tea catechins EGC and ECG are able to alleviate the toxicity of Aβ oligomers and fibrils. Particularly, ECG can cross the blood–brain barrier to reduce the Aβ plaques in the brain of APP/PS1 mice, thereby protecting neurons from injuries. The results manifest the potential of green tea for preventing or ameliorating the symptoms of AD.