School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China.
Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui Road No. 222, Lanzhou, China.
Phytomedicine. 2022 Aug;103:154245. doi: 10.1016/j.phymed.2022.154245. Epub 2022 Jun 6.
Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid β plaques (Aβ) is a central hallmark of AD. Accumulating evidence suggest that shifting amyloid precursor protein (APP) metabolism pathway to non-amyloidogenic ways and inducing autophagy play key roles in AD pathology. In published reports, there is no research on the APP metabolic process of Terminalia chebula Retz. (T. Chebula).
The study aims to assess the effects of T. Chebula in AD transgenic SH-SY5Y cells to determine its underlying mechanisms on reducing Aβ level by regulating APP metabolic process.
The effects of T. Chebula water extract (TWE) on APPswe transgenic SH-SY5Y cells were analyzed by cell viability. ELISA used to quantify extracellular Aβ and Aβ generations. Western blot and RT-PCR assays were chosen to detect the expression of proteins and genes. The acridine orange (AO) stain was used to label autophagic-vesicles.
Treatment with TWE significantly suppressed the Aβ and Aβ generations of APPswe transgenic cells. TWE inhibited amyloidogenic pathway by reducing BACE1 expression, and promote non-amyloidogenic pathway by inducing ADAM10 level of APP metabolism. Additionally, TWE induced autophagy in APPswe transgenic cells involved in APP metabolism to shift the balance to non-amyloidogenic pathway.
In summary, our finding first time expounded that TWE can inhibit the generation of Aβ and Aβ in APPswe transgenic SH-SY5Y cells, which were regulated APP metabolism tends to non-amyloid metabolism pathway and mediated by autophagy. The results presented a novel finding for AD treatment of traditional natural medicines.
阿尔茨海默病（AD）是最常见的神经退行性疾病。淀粉样β斑块（Aβ）的沉积是 AD 的一个中心标志。越来越多的证据表明，将淀粉样前体蛋白（APP）代谢途径转向非淀粉样生成途径和诱导自噬在 AD 病理中起着关键作用。在已发表的报告中，没有关于诃子（T. Chebula）的 APP 代谢过程的研究。
本研究旨在评估诃子水提物（TWE）对 AD 转基因 SH-SY5Y 细胞的影响，通过调节 APP 代谢过程来确定其降低 Aβ 水平的潜在机制。
通过细胞活力分析来分析 TWE 对 APPswe 转基因 SH-SY5Y 细胞的影响。ELISA 用于定量细胞外 Aβ 和 Aβ 生成。选择 Western blot 和 RT-PCR 测定来检测蛋白质和基因的表达。吖啶橙（AO）染色用于标记自噬小泡。
TWE 处理显著抑制了 APPswe 转基因细胞的 Aβ 和 Aβ 生成。TWE 通过降低 BACE1 的表达抑制淀粉样蛋白形成途径，并通过诱导 APP 代谢中的 ADAM10 水平促进非淀粉样蛋白形成途径。此外，TWE 诱导 APPswe 转基因细胞中的自噬参与 APP 代谢，以将平衡转向非淀粉样蛋白形成途径。
总之，我们的研究结果首次阐明，TWE 可以抑制 APPswe 转基因 SH-SY5Y 细胞中 Aβ 和 Aβ 的生成，这是通过调节 APP 代谢向非淀粉样代谢途径和自噬介导的。研究结果为传统天然药物治疗 AD 提供了新的发现。
