School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.
Department of Bioengineering, Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong 519041, China.
Food Funct. 2020 Mar 26;11(3):2427-2438. doi: 10.1039/c9fo02927c.
Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens elderly health. Schisandrin (SCH) and nootkatone (NKT) are two core components derived from Alpinia oxyphylla-Schisandra chinensis herb pair (ASHP), a traditional Chinese medicine formulation. Previous studies demonstrated that the combination of NKT and SCH exerted a neuroprotective effect in AD mouse models. The present study was undertaken to investigate whether there was a synergistic effect between NKT and SCH and the possible mechanism in Aβ1-42 induced PC12 cells. SCH (50 μM) and NKT (10 μM) had the most notable inhibitory effect on the level of Aβ secreted by cells. Treatment with NKT + SCH activated the PI3K/AKT/Gsk-3β/mTOR pathway. Inflammation related proteins such as NF-κB, IKK, IL-1β, IL-6 and TNF-α were decreased. The levels of cleaved-Caspase3 and LC3-II were reduced, indicating that apoptosis and autophagy were inhibited. These results revealed that NKT + SCH exerted a neuroprotective effect via the PI3K/AKT pathway, inhibiting inflammation, apoptosis and autophagy.
阿尔茨海默病（AD）是一种严重威胁老年人健康的神经退行性疾病。五味子素（SCH）和诺卡酮（NKT）是来源于五味子-南五味子草药对（ASHP）的两种核心成分，是一种传统的中药配方。先前的研究表明，NKT 和 SCH 的联合使用对 AD 小鼠模型具有神经保护作用。本研究旨在探讨 NKT 和 SCH 之间是否存在协同作用及其在 Aβ1-42 诱导的 PC12 细胞中的可能机制。SCH（50 μM）和 NKT（10 μM）对细胞分泌的 Aβ 水平具有最显著的抑制作用。用 NKT+SCH 处理可激活 PI3K/AKT/Gsk-3β/mTOR 通路。NF-κB、IKK、IL-1β、IL-6 和 TNF-α 等炎症相关蛋白的水平降低。Cleaved-Caspase3 和 LC3-II 的水平降低，表明细胞凋亡和自噬受到抑制。这些结果表明，NKT+SCH 通过 PI3K/AKT 通路发挥神经保护作用，抑制炎症、细胞凋亡和自噬。
