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杜仲提取物对鱼藤酮诱导的帕金森病模型小鼠神经退行性变的中枢和肠神经保护作用。

Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse.

机构信息

Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

Department of Medical Neurobiology, Okayama University Medical School.

出版信息

Acta Med Okayama. 2022 Aug;76(4):373-383. doi: 10.18926/AMO/63889.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone-induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification.

摘要

帕金森病(PD)是一种中枢和周围/肠神经系统的进行性神经退行性疾病。氧化应激和神经炎症与 PD 的发病机制有关,这表明抗氧化和抗炎化合物可能是 PD 的神经保护剂。杜仲(EU)是一种传统的草药,通过抗炎和抗氧化特性发挥神经保护作用。我们之前的研究表明,绿原酸(EU 的一种成分)治疗可预防 PD 模型中中枢和肠神经系统的神经变性。在这项研究中,我们研究了 EU 提取物(EUE)对低剂量鱼藤酮诱导的 PD 模型小鼠黑质致密部(SNpc)多巴胺能神经退行性变、神经胶质反应和α-突触核蛋白表达以及肠道肠神经退行性变的影响。每日口服 EUE 可改善 SNpc 中的多巴胺能神经退行性变和α-突触核蛋白的积累。EUE 治疗抑制了鱼藤酮诱导的总星形胶质细胞数量和抗氧化分子金属硫蛋白表达的减少。EUE 还可防止鱼藤酮诱导的小胶质细胞激活。此外,EUE 治疗对 PD 模型中的肠道神经元丢失具有保护作用。这些结果表明,EU 通过胶质细胞修饰对鱼藤酮诱导的帕金森病小鼠的中枢和肠神经系统发挥神经保护作用。

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