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根皮苷可减轻 MPTP 诱导的帕金森病小鼠的行为缺陷和神经炎症反应。

Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice.

机构信息

Department of Neurology, Xi'an Jiaotong University Affiliated Xi'an Central Hospital, No.161, Xiwu Road, Xincheng District, Xi'an, Shaanxi Province 710003, China.

Department of Ophthalmology, Xi'an Jiaotong University Affiliated Xi'an Central Hospital, No.161, Xiwu Road, Xincheng District, Xi'an, Shaanxi Province 710003, China.

出版信息

Life Sci. 2019 Sep 1;232:116600. doi: 10.1016/j.lfs.2019.116600. Epub 2019 Jun 25.

DOI:10.1016/j.lfs.2019.116600
PMID:31251998
Abstract

Neuroinflammation is one of the significant neuropathological conditions in Parkinson's disease (PD) which is due to microglial and astrocytes activation leads to progressive dopaminergic neuronal loss. To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ability to prevent the progression of neurodegeneration. Therefore, a better approach to develop a multi potent drug of natural origin would be beneficial in managing the disease. Therefore, the present study aimed to investigate the neuroprotective and anti-inflammatory effects of PHL by exploring its neuroprotective mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) induced PD in mice. MPTP intoxication in mice cause motor abnormalities, decreased dopamine (DA) levels, reduced tyrosine hydroxylase (TH) enzyme protein expression and inflammation which were effectively restored by PHL. Moreover gliotic specific inflammatory markers like glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (Iba-1), iNOS and COX-2 were found to be expressed more in MPTP intoxicated mice, Further the levels of proinflammatory cytokines like IL-β, IL-6, and TNF-α were significantly upregulated in MPTP intoxicated mice, these deleterious responses were diminished to extend neuroprotection by PHL treatment. Our findings strongly suggest PHL as a potent therapeutic agent in treating PD.

摘要

神经炎症是帕金森病(PD)的重要神经病理学条件之一,这是由于小胶质细胞和星形胶质细胞的激活导致多巴胺能神经元进行性丧失。迄今为止,目前的 PD 药物仅提供对症缓解,具有不良反应,并且缺乏预防神经退行性变进展的能力。因此,开发一种具有天然来源的多效药物的更好方法将有益于管理该疾病。因此,本研究旨在通过探索其在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 小鼠中的神经保护机制,研究 PHL 的神经保护和抗炎作用。MPTP 中毒可导致小鼠运动异常、多巴胺(DA)水平降低、酪氨酸羟化酶(TH)酶蛋白表达减少和炎症,而 PHL 可有效恢复这些症状。此外,在 MPTP 中毒的小鼠中发现胶质特异性炎症标志物如胶质纤维酸性蛋白(GFAP)、钙结合接头蛋白-1(Iba-1)、iNOS 和 COX-2 的表达增加,进一步的促炎细胞因子如 IL-β、IL-6 和 TNF-α的水平在 MPTP 中毒的小鼠中显著上调,这些有害反应通过 PHL 治疗得到缓解以延长神经保护作用。我们的研究结果强烈表明 PHL 是治疗 PD 的有效治疗剂。

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