Center for Excellence in Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa, FL 33612, USA.
Curr Alzheimer Res. 2009 Dec;6(6):564-71. doi: 10.2174/156720509790147115.
Inhibition of beta-amyloid (A beta) accumulation and A beta fibril (fA beta) formation from A beta are attractive therapeutic targets for the treatment of Alzheimer's disease (AD). While previous studies have shown anti-amyloidogenic effects of curcumin in vitro and in vivo, no studies have examined optimized turmeric extracts enriched in curcuminoids or turmerones. Three standardized turmeric extracts, HSS-838, HSS-848, and HSS-888, were prepared with different chemical profiles to investigate their potential therapeutic benefits for AD. These extracts were fingerprinted by DART TOF-MS to reveal the significant chemical complexity. In addition four curcuminoids (curcumin, tetrahydrocurcumin, demethoxycurcumin and bisdemethoxycurcumin) were also examined. We measured the effects of the extracts and curcuminoids, on the aggregation of A beta by using a thioflavin T cell-free assay and the secretion of A beta from human neuronal cells (SweAPP N2A cells) in vitro. All three extracts and the curcuminoids showed dose-dependent inhibition of fA beta aggregation from A beta(1-42) in the cell-free assay, with IC(50) values of <or= 5 microg/mL. However, only HSS-888, curcumin and demethoxycurcumin significantly decreased A beta secretion (approximately 20%) in SweAPP N2A cells. Interaction matrices were used to examine possible synergistic interactions between HS-888 and the other extracts and the individual curcuminoids on A beta aggregation. Only simple additive effects were observed for the A beta aggregation inhibition, supporting the notion that the known curcuminoids are not strong inhibitors of this activity. However, HSS-888 showed strong inhibition of A beta aggregation and secretion, thus indicating that there are novel bioactive molecules in this extract that might be important leads for future AD drug discovery efforts.
抑制β-淀粉样蛋白（Aβ）的积累和 Aβ纤维（fAβ）的形成是治疗阿尔茨海默病（AD）的有吸引力的治疗靶点。虽然以前的研究表明姜黄素在体外和体内具有抗淀粉样变性作用，但没有研究检查过富含姜黄素或姜酮的优化姜黄提取物。三种标准化姜黄提取物 HSS-838、HSS-848 和 HSS-888 具有不同的化学特征，用于研究其对 AD 的潜在治疗益处。这些提取物通过 DART TOF-MS 进行了指纹图谱分析，以揭示其显著的化学复杂性。此外，还检查了四种姜黄素（姜黄素、四氢姜黄素、脱甲氧基姜黄素和双脱甲氧基姜黄素）。我们通过使用无细胞硫黄素 T 测定法测量了提取物和姜黄素对 Aβ聚集的影响，以及在体外从人神经元细胞（SweAPP N2A 细胞）中分泌 Aβ。所有三种提取物和姜黄素在无细胞测定中均显示出剂量依赖性抑制 Aβ（1-42）纤维的聚集，IC50 值均<或=5μg/mL。然而，只有 HSS-888、姜黄素和脱甲氧基姜黄素显著降低了 SweAPP N2A 细胞中 Aβ的分泌（约 20%）。使用相互作用矩阵检查 HSS-888 与其他提取物和单个姜黄素对 Aβ聚集的可能协同相互作用。仅观察到 Aβ聚集抑制的简单加性作用，这表明已知的姜黄素不是这种活性的强抑制剂。然而，HSS-888 显示出对 Aβ聚集和分泌的强烈抑制作用，因此表明该提取物中存在新型的生物活性分子，这些分子可能是未来 AD 药物发现工作的重要先导物。
