Key Laboratory of Radiopharmaceuticals Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Pharm Biol. 2011 Oct;49(10):1008-13. doi: 10.3109/13880209.2011.559585.
The destabilization of β-amyloid (Aβ) peptide aggregates and the protection of functional cells are the attractive therapeutic strategies for Alzheimer's disease (AD). Some active ingredients of Salvia miltiorrhiza f. alba C.Y.Wu & H.W.Li (Lamiaceae) (SM) have attracted increasing attention for the treatment of neurodegenerative diseases.
Salvianic borneol ester (SBE) is a new compound based on SM formulas. The present study was designed to examine the anti-amyloid effects and neuroprotection of SBE in vitro.
The destabilizing effects of SBE and its related compounds (salvianic acid A and borneol) on preformed Aβ oligomers were measured by using fluorescence spectroscopy with thioflavin T (ThT) and the destabilizing effects of SBE were further confirmed visually by transmission electron microscopy (TEM). The neuroprotective effects of SBE against hydrogen peroxide (H(2)O(2))-induced toxicity in human neuroblastoma cells (SH-SY5Y) and motor neuron hybridoma cells (VSC 4.1) were shown by MTT assay and morphological observation.
SBE showed the most significant destabilizing effect, though the mixture of salvianic acid A and borneol also destabilized Aβ1-40 oligomers. The destabilizing activity of salvianic acid A or borneol alone was not significant. SBE destabilized Aβ1-40 oligomers in dose- and time-dependent manners and the destabilizing effect could also be seen in the photographs of TEM. Furthermore, SBE could protect SH-SY5Y cells and VSC 4.1 cells against H(2)O(2)-induced toxicity in a dose-dependent manner.
SBE had the bifunctional activities of anti-amyloid and neuroprotection. It may have therapeutic potential for AD and be an alternative lead compound for developing new drugs against AD.
β-淀粉样蛋白（Aβ）肽聚集物的稳定和功能细胞的保护是治疗阿尔茨海默病（AD）的有吸引力的治疗策略。丹参（唇形科）的一些活性成分引起了人们对治疗神经退行性疾病的越来越多的关注。
丹参醇基酯（SBE）是基于 SM 配方的新型化合物。本研究旨在体外研究 SBE 的抗淀粉样蛋白作用和神经保护作用。
使用噻唑蓝（ThT）荧光光谱法测量 SBE 及其相关化合物（丹酚酸 A 和冰片）对预形成的 Aβ寡聚物的去稳定作用，并通过透射电子显微镜（TEM）进一步直观地确认 SBE 的去稳定作用。通过 MTT 测定和形态观察显示 SBE 对过氧化氢（H2O2）诱导的人神经母细胞瘤细胞（SH-SY5Y）和运动神经元杂交瘤细胞（VSC 4.1）毒性的神经保护作用。
SBE 显示出最显著的去稳定作用，尽管丹酚酸 A 和冰片的混合物也使 Aβ1-40 寡聚物去稳定。丹酚酸 A 或冰片单独的去稳定作用不显著。SBE 以剂量和时间依赖的方式使 Aβ1-40 寡聚物去稳定，并且在 TEM 的照片中也可以看到去稳定作用。此外，SBE 可以剂量依赖性方式保护 SH-SY5Y 细胞和 VSC 4.1 细胞免受 H2O2 诱导的毒性。
SBE 具有抗淀粉样蛋白和神经保护的双重作用。它可能对 AD 具有治疗潜力，并可能成为开发治疗 AD 的新药的替代先导化合物。
