The neuroprotective effect of schisandrol A on 6-OHDA-induced PD mice may be related to PI3K/AKT and IKK/IκBα/NF-κB pathway
The neuroprotective effect of schisandrol A on 6-OHDA-induced PD mice may be related to PI3K/AKT and IKK/IκBα/NF-κB pathway
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DOI：
10.1016/j.exger.2019.110743
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发表时间：
2019-12-01
影响因子：
3.9
通讯作者：
Jia, Ying
中科院分区：
文献类型：
--
作者：
Yan, Tingxu;Sun, Yingying;Jia, Ying
帕金森病是第二大常见的神经退行性疾病。其主要病理特征是黑质-纹状体多巴胺能神经元功能障碍，导致DA释放不足，引起运动症状，并伴有非运动症状。五味子醇甲属于木脂素类成分，具有抗炎、抗氧化和神经保护作用。本实验采用C57 BL/6 J雄性小鼠前脑内侧束注射6-OHDA建立模型。采用旷场实验和极杆实验检测小鼠运动功能，蔗糖偏好实验检测小鼠抑郁样行为，Y迷宫检测小鼠记忆功能。结果发现，五味子醇甲（20 mg/kg/d）能显著改善6-OHDA诱导的PD小鼠的运动症状，减轻抑郁样症状和记忆障碍。然后通过H.E.，ELISA检测试剂盒和Western blot。结果表明，五味子醇甲可增强小鼠脑内PI 3 K/AKT通路，抑制IKK/I kappa B alpha/NF-κ B B通路，减轻神经元炎症反应和氧化应激，提高DA能神经元存活率。这些结果表明，五味子醇甲有望成为改善帕金森病的潜在药物。
Parkinson's disease is the second most common neurodegenerative disease. Its main pathological feature is the substantial nigra-striatum dopaminergic neuronal dysfunction, which causes insufficient release of DA, induces motor symptoms, and is accompanied by nonmotor symptoms. Schisandrol A belongs to lignan components and has anti-inflammatory, antioxidant and neuroprotective effects. In this experiment, we injected 6-OHDA into medial forebrain bundle of C57BL/6J male mice to establish the model. The motor function of mice was examined by open field test and pole test, the depression-like behavior of mice was examined by sucrose preference test and the memory function was examined by Y maze. We found that schisandrol A (20 mg/kg/d) could significantly improve the motor symptoms, and alleviate the depression-like symptoms and memory dysfunction of PD mice induced by 6-OHDA. Then we studied the neuroprotective mechanism of schisandrol A by H.E., ELISA assay kits and Western blot. Results showed that schisandrol A may enhance the PI3K/AKT pathway, inhibit the IKK/I kappa B alpha/NF-kappa B pathway, reduce neuronal inflammation and oxidative stress, and enhance the survival of DA neurons in the brain of mice. These results indicate that schisandrol A is expected to be a potential drug for improving Parkinson's disease.