Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
J Agric Food Chem. 2011 Mar 9;59(5):1683-9. doi: 10.1021/jf103822h. Epub 2011 Feb 8.
Alzheimer's disease is neuropathologically characterized by amyloid β-protein (Aβ) deposition, resulting in neurotoxicity. Herein, we focused on the prevention of anthocyanins from amyloid-mediated neurodysfunction. The data demonstrated that combined exposure of Aβ(1-40) and Aβ(25-35) to Neuro-2A cells resulted in reactive oxygen species (ROS) production and perturbation of calcium homeostasis. The expressions of LXRα, ApoE, ABCA1, and seladin-1 genes were significantly down-regulated upon Aβ challenge. β-Secretase, the rate-limiting enzyme that catalyzes amyloid precursor protein transform to Aβ, was up-regulated by Aβ treatment. For the duration of Aβ stimulation, malvidin (Mal) or oenin (Oen; malvidin-3-O-glucoside) was added, and the protective effects were observed. Mal and Oen showed protective effects against Aβ-induced neurotoxicity through blocking ROS formation, preserving Ca(2+) homeostasis, and preventing Aβ-mediated perturbation of certain genes involved in Aβ metabolism and cellular defense. The present study implicates anthocyanin as a potential therapeutic candidate for the prevention of amyloid-mediated neurodysfunction.
阿尔茨海默病在神经病理学上的特征是淀粉样 β-蛋白(Aβ)沉积,导致神经毒性。在此,我们专注于预防花青素介导的神经功能障碍。研究数据表明,Aβ(1-40)和 Aβ(25-35)联合暴露于 Neuro-2A 细胞中会导致活性氧(ROS)的产生和钙稳态的紊乱。Aβ 刺激后,LXRα、ApoE、ABCA1 和 seladin-1 基因的表达显著下调。β-分泌酶是一种限速酶,可催化淀粉样前体蛋白转化为 Aβ,Aβ 处理会使其上调。在 Aβ 刺激期间添加矢车菊素(Mal)或圣草酚(Oen;矢车菊素-3-O-葡萄糖苷),观察到保护作用。Mal 和 Oen 通过阻断 ROS 形成、维持 Ca(2+)稳态以及防止 Aβ 介导的 Aβ 代谢和细胞防御相关基因的紊乱,对 Aβ 诱导的神经毒性具有保护作用。本研究表明,花青素可能是预防淀粉样蛋白介导的神经功能障碍的潜在治疗候选物。