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槲皮素靶向Nrf2信号通路在预防和治疗神经疾病中的应用:综述与新进展

Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments.

作者信息

Zamanian Mohammad Yasin, Soltani Afsaneh, Khodarahmi Zahra, Alameri Ameer A, Alwan Athemar M R, Ramírez-Coronel Andrés Alexis, Obaid Rasha Fadhel, Abosaooda Munther, Heidari Mahsa, Golmohammadi Maryam, Anoush Mahdieh

机构信息

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Fundam Clin Pharmacol. 2023 Dec;37(6):1050-1064. doi: 10.1111/fcp.12926. Epub 2023 Jun 16.

Abstract

BACKGROUND

Neurological disorders (NLDs) are widely acknowledged as a significant public health concern worldwide. Stroke, Alzheimer's disease (AD), and traumatic brain injury (TBI) are three of these disorders that have sparked major study attention. Neurological dysfunction, protein buildup, oxidation and neuronal injury, and aberrant mitochondria are all prevalent neuropathological hallmarks of these disorders. The signaling cascade of nuclear factor erythroid 2 related factor 2 (Nrf2) shares all of them as a common target. Several studies have found that overexpression of Nrf2 is a promising treatment method in NLDs. Effective treatment of these disorders continues to be a universal concern regardless of various medicines. In order to treat a variety of neurological problems, organic remedies may provide an alternative treatment. It has been demonstrated that polyphenols like quercetin (Que) offer considerable capabilities for treating NLDs. One of Que's greatest key targets, Nrf2, has the capacity to control the production of a number of cytoprotective enzymes that exhibit neuroprotective, detoxifying, and antioxidative effects. Additionally, Que enhanced the expression of Nrf2 and inhibited alterations in the shape and death of neurons in the hippocampus.

OBJECTIVE

In this review, we have focused on Que's medicinal prospects as a neuroprotective drug.

METHODS

PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study.

RESULTS

The findings of this research demonstrate that (1) Que protected the blood-brain barrier via stimulating Nrf2 in animal stroke, which alleviated ischemic reperfusion and motor dysfunction. (2) By triggering the Nrf2 pathway, Que reduced the neuroinflammation and oxidative damage brought on by TBI in the cortex. (3) In an experimental model of AD, Que enhanced cognitive function by decreasing A1-4, antioxidant activity, and Nrf2 levels in the brain.

CONCLUSION

We discuss recent research on Que-mediated Nrf2 expression in the management of several NLDs in this paper.

摘要

背景

神经疾病(NLDs)被广泛认为是全球重大的公共卫生问题。中风、阿尔茨海默病(AD)和创伤性脑损伤(TBI)是引发大量研究关注的其中三种疾病。神经功能障碍、蛋白质堆积、氧化和神经元损伤以及线粒体异常都是这些疾病常见的神经病理学特征。核因子红细胞2相关因子2(Nrf2)的信号级联反应将所有这些作为共同靶点。多项研究发现,Nrf2的过表达是神经疾病中有前景的治疗方法。尽管有各种药物,但有效治疗这些疾病仍然是一个普遍关注的问题。为了治疗各种神经问题,有机疗法可能提供一种替代治疗方法。已证明,像槲皮素(Que)这样的多酚具有治疗神经疾病的显著能力。Que最关键的靶点之一Nrf2能够控制多种具有神经保护、解毒和抗氧化作用的细胞保护酶的产生。此外,Que增强了Nrf2的表达,并抑制了海马体中神经元的形态改变和死亡。

目的

在本综述中,我们重点关注了Que作为神经保护药物的药用前景。

方法

使用PubMed、Scopus、Science Direct和谷歌学术搜索本研究的文章。

结果

本研究结果表明:(1)在动物中风模型中,Que通过刺激Nrf2保护血脑屏障,减轻了缺血再灌注和运动功能障碍。(2)通过触发Nrf2途径,Que减少了TBI在皮质中引发的神经炎症和氧化损伤。(3)在AD实验模型中,Que通过降低大脑中的Aβ1-4、抗氧化活性和Nrf2水平增强了认知功能。

结论

在本文中,我们讨论了Que介导的Nrf2表达在几种神经疾病管理中的最新研究。

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