The protective effects of citrullus colocynthis on inhibiting oxidative damage and autophagy-associated cell death in Parkinson's disease

The protective effects of citrullus colocynthis on inhibiting oxidative damage and autophagy-associated cell death in Parkinson's disease
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西瓜对抑制帕金森病氧化损伤和自噬相关细胞死亡的保护作用

DOI:
10.1016/j.jtice.2019.04.003
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发表时间:
2019-07-01
影响因子:
5.7
通讯作者:
Liu, Bo
Liu, Bo
中科院分区:
工程技术3区
文献类型:
--
作者:
Chen, Yanmei;Sa, Yuliang;Liu, Bo

文献摘要

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香瓜(Citrullus colocynthis, CC)是一种民族药,分布在中国新疆维吾尔自治区,是治疗风湿性关节炎或由黑胆异常引起的疾病的传统药物。在此,我们研究了CC对帕金森病(PD)的治疗作用及其保护机制。首先,通过一系列行为学实验评价CC对mptp诱导的PD小鼠模型的影响。运动迟缓、记忆减退和攀爬时间均有显著改善。同时免疫组化和western blot检测酪氨酸羟化酶(TH)和a-synuclein的改善。此外,还发现CC可通过降低超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和提高丙二醛(MDA)活性来缓解PD小鼠脑组织氧化应激。并结合生物信息学方法分析了其可能的保护机制。随后,利用免疫荧光、流式细胞术和western blot验证其作用机制。结果表明,CC可通过ROS-AMPK-ULK1信号通路抑制MPP+诱导的SH-SY5Y细胞的自噬,从而减轻氧化损伤。综上所述,本研究验证了CC对PD具有良好的神经保护作用,可以减轻氧化应激,抑制自噬细胞死亡。(C) 2019台湾省化学工程师学会。Elsevier B.V.版权所有。
Citrullus colocynthis (CC), an ethnic medicine, distributed in Xinjiang Uygur Autonomous Region of China, is a traditional remedy for rheumatic arthritis or diseases caused by abnormal black biliary. Here, we investigated the therapeutic effect of CC on Parkinson's disease (PD) and its protective mechanisms. Firstly, the effects of CC on MPTP-induced PD mouse model were evaluated by a series of behavioral tests. Significant improvement of bradykinesia and memory reduction and reduction of climbing time were observed. Meanwhile, improvement of tyrosine hydroxylase (TH) and a-synuclein was also detected by immunohistochemical and western blot analysis. Additionally, it was also found that CC could relieve the oxidative stress in PD mouse brain tissues by decreasing activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and increasing activity of malondialdehyde (MDA). Moreover, possible protective mechanisms were analyzed by a set of combined bioinformatics methods. Subsequently, the mechanism was verified using immunofluorescence, flow cytometry and western blot. Results showed that CC could reduce oxidative damage by inhibiting the autophagy via ROS-AMPK-ULK1 signaling pathway in MPP+-induced SH-SY5Y cells. In conclusion, the present study validated that CC has a promising neuroprotective effect against PD, which can reduce oxidative stress and inhibiting autophagic cell death. (C) 2019 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.