School of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, PR China.
Institute of Nautical Medicine, Nantong University, Nantong 226019, PR China.
Bioorg Chem. 2020 Dec;105:104382. doi: 10.1016/j.bioorg.2020.104382. Epub 2020 Oct 15.
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 Cu/Zn-induced or self-assembled Aβ 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 Cu and Zn, and diminish the Cu- or Zn-induced or self-assembled Aβ aggregates; they also modulate the Cu/Zn-Aβ 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.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是进行性积累老年斑，老年斑主要由错误折叠的淀粉样β肽（Aβ）组成。Aβ 聚集物被认为是 AD 发病机制中的一个关键因素，影响人体神经系统。采用硫黄素 T 荧光光谱法、电感耦合等离子体质谱法、紫外-可见光谱法、透射电子显微镜、银染、免疫组织化学和免疫荧光法，研究了茶衍生多酚化合物（-）-表没食子儿茶素（EGC）和（-）-表儿茶素-3-没食子酸酯（ECG）对 AD 的治疗潜力，以评估它们对 Cu/Zn 诱导或自组装 Aβ 聚集的影响。EGC 和 ECG 轻度结合 Cu 和 Zn，并减少 Cu 或 Zn 诱导或自组装 Aβ 聚集物；它们还通过减少 ROS 的产生来调节 Cu/Zn-Aβ 对小鼠神经母细胞瘤 Neuro-2a 细胞的神经毒性。金属螯合、氢键或范德华力可能驱动多酚化合物与 Aβ 之间的相互作用。结果表明，绿茶儿茶素 EGC 和 ECG 能够减轻 Aβ 低聚物和纤维的毒性。特别是，ECG 可以穿过血脑屏障，减少 APP/PS1 小鼠大脑中的 Aβ 斑块，从而保护神经元免受损伤。结果表明绿茶具有预防或改善 AD 症状的潜力。
