Department of Otolaryngology Head and Neck Surgery, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Urology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China.
Int J Mol Med. 2019 Mar;43(3):1406-1416. doi: 10.3892/ijmm.2019.4058. Epub 2019 Jan 10.
By analyzing the L‑glutamic acid (L‑Glu)‑induced apoptosis of PC12 cells and an AlCl3 combined with D‑galactose (D‑gal)‑developed Alzheimer's disease (AD) mouse model, the protective effects of isoastilbin (IAB) against AD were systematically investigated in the present study. Pre‑incubation with IAB for 3 h prior to treatment with 25 mM L‑Glu decreased cell viability and inhibited apoptosis, suppressed the accumulation of intracellular reactive oxygen species, and restored mitochondrial membrane potential in PC12 cells induced by L‑Glu. In mice with AD, the reduced escape latency time in the water maze test, suppressed chronic movement in the center area of an open field test and enhanced ability to seek hidden food in a Y maze test indicated that abnormal behaviors had improved after 28 days of treatment with IAB. Furthermore, IAB reduced the deposition of amyloid β (Aβ) and the expression of phosphorylated‑Tau in the mouse brain and enhanced the serum levels of Aβ. IAB ameliorated the oxidative stress via modulating the levels of associated enzymes and improved the functioning of the central cholinergic system, as indicated by an increase in acetylcholine and choline acetyltransferase concentrations. The expression levels of acetylcholine esterase were reduced in the mouse brain in response to IAB pre‑treatment. In cells and brain tissue, IAB regulated the expression levels of pro‑ and anti‑apoptotic proteins and enhanced the nuclear levels of NF‑E2p45‑related factor 2 (Nrf2); subsequently, IAB further enhanced the expression of superoxide dismutase 1, catalase, and heme oxygenase‑1 and ‑2. The findings of the present study indicated that the protection of IAB against AD is at least partially associated with its antioxidation and anti‑apoptotic properties.
通过分析 L-谷氨酸（L-Glu）诱导的 PC12 细胞凋亡和 AlCl3 联合 D-半乳糖（D-gal）建立的阿尔茨海默病（AD）小鼠模型，本研究系统研究了异落新妇苷（IAB）对 AD 的保护作用。在用 25mM L-Glu 处理之前，用 IAB 预孵育 3 小时可降低细胞活力并抑制细胞凋亡，抑制细胞内活性氧的积累，并恢复 L-Glu 诱导的 PC12 细胞中线粒体膜电位。在 AD 小鼠中，水迷宫测试中逃避潜伏期时间的减少、旷场测试中心区域慢性运动的抑制以及 Y 迷宫测试中寻找隐藏食物能力的增强表明，经过 28 天的 IAB 治疗后，异常行为得到改善。此外，IAB 减少了小鼠大脑中淀粉样β（Aβ）的沉积和磷酸化 Tau 的表达，并提高了血清中 Aβ的水平。IAB 通过调节相关酶的水平改善了氧化应激，提高了中枢胆碱能系统的功能，乙酰胆碱和胆碱乙酰转移酶浓度增加。在小鼠大脑中，乙酰胆碱酯酶的表达水平在 IAB 预处理后降低。在细胞和脑组织中，IAB 调节了促凋亡和抗凋亡蛋白的表达水平，并增强了核因子 E2 相关因子 2（Nrf2）的核水平；随后，IAB 进一步增强了超氧化物歧化酶 1、过氧化氢酶和血红素加氧酶-1 和 -2 的表达。本研究的结果表明，IAB 对 AD 的保护作用至少部分与其抗氧化和抗凋亡特性有关。
