Department of Biotechnology, Chonnam National University, San96-1, Dun-Duk Dong, Yeosu, Chonnam 550-749, Korea.
Department of Refrigeration Engineering, Chonnam Natational University, San96-1, Dun-Duk Dong, Yeosu, Chonnam 550-749, Korea.
Molecules. 2020 May 16;25(10):2334. doi: 10.3390/molecules25102334.
Alzheimer's disease (AD) is the most frequent type of dementia affecting memory, thinking and behaviour. The major hallmark of the disease is pathological neurodegeneration due to abnormal aggregation of Amyloid beta (Aβ) peptides generated by β- and γ-secretases via amyloidogenic pathway. Purpose of the current study was to evaluate the effects of theasaponin E1 on the inhibition of Aβ producing β-, γ-secretases (BACE1, PS1 and NCT) and acetylcholinesterase and activation of the non-amyloidogenic APP processing α-secretase (ADAM10). Additionally, theasaponin E1 effects on Aβ degrading and clearing proteins neprilysin and insulin degrading enzyme (IDE). The effect of theasaponin E1 on these crucial enzymes was investigated by RT-PCR, ELISA, western blotting and fluorometric assays using mouse neuroblastoma cells (SweAPP N2a). theasaponin E1 was extracted and purified from green tea seed extract via HPLC, and N2a cells were treated with different concentrations for 24 h. Gene and protein expression in the cells were measured to determine the effects of activation and/or inhibition of theasaponin E1 on β- and γ-secretases, neprilysin and IDE. Results demonstrated that theasaponin E1 significantly reduced Aβ concentration by activation of the α-secretase and neprilysin. The activities of β- and γ-secretase were reduced in a dose-dependent manner due to downregulation of , presenilin, and nicastrin. Similarly, theasaponin E1 significantly reduced the activity of acetylcholinesterase. Overall, from the results it is concluded that green tea seed extracted saponin E1 possess therapeutic significance as a neuroprotective natural product recommended for the treatment of Alzheimer's disease.
阿尔茨海默病（AD）是最常见的痴呆类型，影响记忆、思维和行为。该疾病的主要标志是病理性神经退行性变，原因是β-和γ-分泌酶通过淀粉样蛋白途径异常聚集淀粉样β（Aβ）肽。本研究的目的是评估茶皂素 E1 对 Aβ产生β-、γ-分泌酶（BACE1、PS1 和 NCT）和乙酰胆碱酯酶的抑制作用，以及对非淀粉样前体蛋白加工α-分泌酶（ADAM10）的激活作用。此外，还研究了茶皂素 E1 对 Aβ 降解和清除蛋白神经肽酶和胰岛素降解酶（IDE）的影响。通过 RT-PCR、ELISA、western blot 和使用小鼠神经母细胞瘤细胞（SweAPP N2a）的荧光测定法，研究了茶皂素 E1 对这些关键酶的影响。茶皂素 E1 从绿茶籽提取物中通过 HPLC 提取和纯化，并用不同浓度处理 N2a 细胞 24 小时。测量细胞中的基因和蛋白质表达，以确定茶皂素 E1 对β-和γ-分泌酶、neprilysin 和 IDE 的激活和/或抑制作用。结果表明，茶皂素 E1 通过激活α-分泌酶和 neprilysin 显著降低 Aβ 浓度。由于下调，β-和γ-分泌酶的活性呈剂量依赖性降低，早老素和 nicastrin。同样，茶皂素 E1 显著降低乙酰胆碱酯酶的活性。总的来说，从结果可以得出结论，绿茶籽提取的皂素 E1 作为一种具有神经保护作用的天然产物，具有治疗意义，推荐用于治疗阿尔茨海默病。
