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天然产物对亨廷顿病的保护作用:科学证据概述及其作用机制的理解。

Protective Effect of Natural Products against Huntington's Disease: An Overview of Scientific Evidence and Understanding Their Mechanism of Action.

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, 30450 Perak, Malaysia.

School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Selangor Darul Ehsan, Malaysia.

出版信息

ACS Chem Neurosci. 2021 Feb 3;12(3):391-418. doi: 10.1021/acschemneuro.0c00824. Epub 2021 Jan 21.

Abstract

Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against / models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either or models were included in the present review. Behavioral outcomes in the HD model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.

摘要

亨廷顿病(HD)是一种神经退行性疾病,通常在成年期开始,随后逐渐出现特征性的精神障碍和认知及运动功能障碍。据我们所知,目前尚无完全缓解 HD 进展的治疗方法。在各种治疗方法中,大量文献报道证实了天然产物在 HD 实验模型中的药用功效。基于这一信息,本综述简要概述了天然产物对 HD 模型的神经保护机制。从多个科学数据库,包括 PubMed、ScienceDirect、Scopus 和 Google Scholar 中确定了相关研究。在筛选了 2005 年至今的文献后,本综述共纳入了 14 种药用植物物种和 30 种天然分离化合物,这些化合物是基于或模型来研究对 HD 的作用。HD 模型中的行为学结果表明,天然化合物显著减轻了 3-硝基丙酸(3-NP)诱导的记忆丧失和运动不协调。生化改变得到明显缓解,表现为脂质过氧化减少、内源性酶抗氧化剂增加、乙酰胆碱酯酶活性降低和线粒体能量产生增加。有趣的是,某些天然产物治疗后,纹状体中 3-NP 诱导的损伤得到了改善,组织学上可见。总的来说,天然产物通过抗氧化和抗炎特性、维持线粒体功能、抑制细胞凋亡和诱导自噬,在 HD 的临床前研究中提供了不同程度的神经保护作用。

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