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一种多酚类白葡萄汁提取物在实验性自身免疫性脑脊髓炎小鼠模型中的神经保护作用。

Neuroprotective effects of a polyphenolic white grape juice extract in a mouse model of experimental autoimmune encephalomyelitis.

作者信息

Giacoppo Sabrina, Galuppo Maria, Lombardo Giovanni Enrico, Ulaszewska Maria Malgorzata, Mattivi Fulvio, Bramanti Placido, Mazzon Emanuela, Navarra Michele

机构信息

IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, contrada Casazza, 98124, Messina, Italy.

Università degli Studi di Messina, Dipartimento di Scienze del farmaco e dei Prodotti per la Salute, Viale Annunziata, 98168, Messina, Italy.

出版信息

Fitoterapia. 2015 Jun;103:171-86. doi: 10.1016/j.fitote.2015.04.003. Epub 2015 Apr 8.

DOI:10.1016/j.fitote.2015.04.003
PMID:25863350
Abstract

In the last 20 years, wine phenolic compounds have received increasing interest since several epidemiological studies have suggested associations between regular consumption of moderate amount of wine and prevention of certain chronic pathologies, such as neurodegenerative diseases. This study was aimed to investigate the possible neuroprotective role of a polyphenolic white grape juice extract (WGJe) in an experimental mice model of autoimmune encephalomyelitis (EAE), the most commonly used model for multiple sclerosis (MS) in vivo. EAE mimics the main features of MS, including paralysis, weight loss, demyelination, central nervous system (CNS) inflammation and blood-brain barrier (BBB) breakdown. Our study demonstrated that oral administration of WGJe (20 and 40 mg/kg/day) may exert neuroprotective effects against MS, diminishing both clinical signs and histological score typical of disease (lymphocytic infiltration and demyelination). In particular, by western blot, histological evaluations and immunolocalization of the main markers of inflammation, oxidative stress and apoptosis (TNF-α, iNOS, Nitrotyrosine, PARP, Foxp3, Bcl-2, Caspase 3 and DNA fragmentation), we documented that WGJe counteracts the alteration of all these inflammatory and oxidative pathway, without any apparent sign of toxicity. On these bases, we propose this natural product as putative novel helpful tools for the prevention of autoimmune and neurodegenerative diseases such as MS. WGJe could have considerable implication for future therapies of MS, and this study may represents the starting point for further investigation on the role of WGJe in neuroinflammation.

摘要

在过去20年里,葡萄酒中的酚类化合物越来越受到关注,因为多项流行病学研究表明,适量饮用葡萄酒与预防某些慢性疾病(如神经退行性疾病)之间存在关联。本研究旨在探讨一种多酚白葡萄汁提取物(WGJe)在实验性自身免疫性脑脊髓炎(EAE)小鼠模型中的潜在神经保护作用,EAE是体内最常用于多发性硬化症(MS)研究的模型。EAE模拟了MS的主要特征,包括瘫痪、体重减轻、脱髓鞘、中枢神经系统(CNS)炎症和血脑屏障(BBB)破坏。我们的研究表明,口服WGJe(20和40毫克/千克/天)可能对MS具有神经保护作用,可减轻疾病典型的临床症状和组织学评分(淋巴细胞浸润和脱髓鞘)。特别是,通过蛋白质印迹法、组织学评估以及炎症、氧化应激和细胞凋亡主要标志物(TNF-α、iNOS、硝基酪氨酸、PARP、Foxp3、Bcl-2、Caspase 3和DNA片段化)的免疫定位,我们证明WGJe可对抗所有这些炎症和氧化途径的改变,且无任何明显的毒性迹象。基于这些结果,我们提出这种天然产物可能是预防自身免疫性和神经退行性疾病(如MS)的新型有用工具。WGJe可能对MS的未来治疗具有重要意义,本研究可能是进一步研究WGJe在神经炎症中作用的起点。

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