Department of Neurology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
Department of Anesthesiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
J Appl Toxicol. 2022 Nov;42(11):1777-1786. doi: 10.1002/jat.4355. Epub 2022 Jun 16.
Alzheimer's disease (AD) is a neurodegenerative disease in elderly population. Pterostilbene (PTS) is a resveratrol analog with neuroprotective activity. However, the biological mechanisms of PTS in AD progression are largely uncertain. An animal model of AD was established using streptozotocin (STZ)-treated C57BL/6J mice. Monoamine oxidase B (MAOB) expression was analyzed by bioinformatics analysis and detected by western blotting assay. The memory impairment was investigated by Morris water maze test. The levels of Tau hyperphosphorylation and death-related proteins were detected by western blotting analysis. The levels of amyloid β (Aβ) accumulation, oxidative stress-related markers (ROS, MDA, SOD, and GSH), and inflammation-relative markers (TNF-α, IL-1β, IL-6, and p-NF-κB) were measured by ELISA. MAOB expression was increased in hippocampus of AD mice, and it was decreased by PTS. PTS attenuated STZ-induced body weight loss and memory impairment by regulating MAOB. PTS mitigated Aβ accumulation and Tau hyperphosphorylation by regulating MAOB in STZ-treated mice. PTS attenuated neuronal death by decreasing cleaved caspase-3 and Bax levels and increasing Bcl2 expression in hippocampus by regulating MAOB in STZ-treated mice. PTS weakened STZ-induced oxidative stress in hippocampus by decreasing ROS and MDA levels and increasing SOD and GSH levels by regulating MAOB. PTS protected against STZ-induced neuroinflammation in hippocampus by inhibiting TNF-α, IL-1β, IL-6, and p-NF-κB levels through regulating MAOB. In conclusion, PTS alleviates STZ-induced memory impairment, Aβ accumulation, Tau hyperphosphorylation, neuronal death, oxidative stress, and inflammation by decreasing MAOB in AD mice, proving anti-AD potential of PTS.
阿尔茨海默病（AD）是老年人群中的一种神经退行性疾病。白藜芦醇二聚体（PTS）是一种具有神经保护活性的白藜芦醇类似物。然而，PTS 在 AD 进展中的生物学机制在很大程度上尚不清楚。使用链脲佐菌素（STZ）处理的 C57BL/6J 小鼠建立 AD 动物模型。通过生物信息学分析和 Western blot 检测分析单胺氧化酶 B（MAOB）的表达。通过 Morris 水迷宫试验研究记忆障碍。通过 Western blot 分析检测 Tau 过度磷酸化和死亡相关蛋白的水平。通过 ELISA 测量淀粉样β（Aβ）积累、氧化应激相关标志物（ROS、MDA、SOD 和 GSH）和炎症相关标志物（TNF-α、IL-1β、IL-6 和 p-NF-κB）的水平。AD 小鼠海马中的 MAOB 表达增加，而 PTS 则降低了 MAOB 表达。PTS 通过调节 MAOB 减轻了 STZ 引起的体重减轻和记忆障碍。PTS 通过调节 MAOB 减轻了 STZ 处理小鼠的 Aβ 积累和 Tau 过度磷酸化。PTS 通过降低海马中 cleaved caspase-3 和 Bax 水平并增加 Bcl2 表达来减轻神经元死亡，通过调节 MAOB 减轻 STZ 处理小鼠的神经元死亡。PTS 通过调节 MAOB 降低了 ROS 和 MDA 水平，增加了 SOD 和 GSH 水平，减弱了 STZ 诱导的海马氧化应激。PTS 通过抑制 TNF-α、IL-1β、IL-6 和 p-NF-κB 水平来防止 STZ 诱导的海马神经炎症，从而调节 MAOB。总之，PTS 通过降低 AD 小鼠中的 MAOB 减轻了 STZ 诱导的记忆障碍、Aβ 积累、Tau 过度磷酸化、神经元死亡、氧化应激和炎症，证明了 PTS 的抗 AD 潜力。
