β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the formation of β-amyloid peptides (Aβ), which are important in the development of Alzheimer's disease. It has been demonstrated that albiflorin can alleviate Aβ aggregation. However, the mechanism behind this effect is unknown. In our previous work, albiflorin and its four analogues were isolated from Paeonia lactiflora Pall. This study aims to investigate the relationship of these four compounds with BACE1. Our results show that the albiflorin analogue 4-O-galloylalbiflorin (4-O-GA) had the strongest BACE1 inhibitory effect and was also selective for BACE1. Furthermore, docking study of BACE1 with these analogues yielded similar results, whereby 4-O-GA treatment caused the greatest decreases in both the generation of Aβ_1–42 and Aβ_1–40 and in the expression of BACE1 and HIF-1α. Our findings indicate that 4-O-GA exerted significant and selective inhibitory activities against BACE1, potentially providing a useful agent for developing BACE1 inhibitor drugs.

β-位淀粉样蛋白前体蛋白裂解酶1（BACE1）是形成β-淀粉样肽（Aβ）的限速酶，对阿尔茨海默氏病的发展至关重要。已经证明白花素可以减轻Aβ聚集。但是，这种作用的机制尚不清楚。在我们以前的工作中，从bi药中分离了白花素及其四个类似物颇尔 这项研究旨在调查这四种化合物与BACE1的关系。我们的结果表明，白花素类似物4-O-galloylalbiflorin（4-O-GA）具有最强的BACE1抑制作用，并且对BACE1具有选择性。此外，BACE1与这些类似物的对接研究产生了相似的结果，其中4-O-GA处理导致_Aβ1–42和_Aβ1–40的生成以及BACE1和HIF-1α的表达下降最大。我们的发现表明4-O-GA对BACE1发挥了显着的选择性抑制活性，可能为开发BACE1抑制剂药物提供有用的药物。