芍药苷可保护斑马鱼和PC12细胞免受MPP(+)诱导的神经毒性。
Paeonolum protects against MPP(+)-induced neurotoxicity in zebrafish and PC12 cells.
作者信息
Lu Xi-Lin, Lin Yue-Hao, Wu Qi, Su Feng-Juan, Ye Cheng-Hui, Shi Lei, He Bai-Xuan, Huang Fei-Wen, Pei Zhong, Yao Xiao-Li
机构信息
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
出版信息
BMC Complement Altern Med. 2015 Apr 29;15:137. doi: 10.1186/s12906-015-0661-0.
BACKGROUND
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population aged over 65 years old. Mitochondrial defects and oxidative stress actively participate in degeneration of dopaminergic (DA) neurons in PD. Paeonolum, a main component isolated from Moutan cortex, has potent antioxidant ability. Here, we have examined the effects of paeonolum against MPP(+)-induced neurotoxicity in zebrafish and PC12 cells.
METHODS
The overall viability and neurodegeneration of DA neurons was assessed in ETvmat2:green fluorescent protein (GFP) transgenic zebrafish, in which most monoaminergic neurons are labeled by GFP. Damage to PC12 cells was measured using a cell viability assay and assessment of nuclear morphology. Intracellular reactive oxygen species (ROS) and the level of total GSH were assessed. The mitochondrial cell death pathway including mitochondrial membrane potential, cytochrome C release and caspase-3 activity were also examined in PC12 cells.
RESULTS
Paeonolum protected against MPP(+)-induced DA neurodegeneration and locomotor dysfunction in zebrafish in a concentration-dependent manner. Similar neuroprotection was replicated in the PC12 cellular model of MPP(+) toxicity. Paeonolum attenuated MPP(+)-induced intracellular ROS accumulation and restored the level of total GSH in PC12 cells. Furthermore, paeonolum significantly inhibited the mitochondrial cell death pathway induced by MPP(+).
CONCLUSIONS
Collectively, the present study demonstrates that paeonolum protects zebrafish and PC12 cells against MPP(+)-induced neurotoxicity.
背景
帕金森病（PD）是第二常见的神经退行性疾病，影响2%的65岁以上人群。线粒体缺陷和氧化应激积极参与帕金森病中多巴胺能（DA）神经元的变性。芍药苷是从牡丹皮中分离出的主要成分，具有强大的抗氧化能力。在此，我们研究了芍药苷对1-甲基-4-苯基吡啶离子（MPP(+)）诱导的斑马鱼和PC12细胞神经毒性的影响。
方法
在ETvmat2：绿色荧光蛋白（GFP）转基因斑马鱼中评估DA神经元的总体活力和神经变性，其中大多数单胺能神经元用GFP标记。使用细胞活力测定法和核形态评估来测量PC12细胞的损伤。评估细胞内活性氧（ROS）和总谷胱甘肽（GSH）水平。还在PC12细胞中检测了包括线粒体膜电位、细胞色素C释放和半胱天冬酶-3活性在内的线粒体细胞死亡途径。
结果
芍药苷以浓度依赖性方式保护斑马鱼免受MPP(+)诱导的DA神经变性和运动功能障碍。在MPP(+)毒性的PC12细胞模型中也观察到了类似的神经保护作用。芍药苷减轻了MPP(+)诱导的PC12细胞内ROS积累，并恢复了总GSH水平。此外，芍药苷显著抑制了MPP(+)诱导的线粒体细胞死亡途径。
结论
总体而言，本研究表明芍药苷可保护斑马鱼和PC12细胞免受MPP(+)诱导的神经毒性。
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