从生物可及性和多药理角度对黄酮类化合物的老年保护活性进行严格评估

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Roumi Naskar , Anirrban Ghosh , Raja Bhattacharya , Sandipan Chakraborty
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引用次数: 0

摘要

类黄酮是一种常见的天然产品,具有抗氧化、抗炎、抗病毒、抗过敏、保肝、抗癌和保护神经等保健作用。一些研究报告称,类黄酮在临床环境中对改善记忆、学习和认知能力有益。黄酮类化合物的作用机制是通过调节多种信号级联介导的。这种多药理作用使黄酮类化合物成为一种极具吸引力的天然支架,可用于设计和开发治疗阿尔茨海默病和帕金森病等复杂神经系统疾病的新型有效疗法。黄酮类化合物可抑制与神经退行性疾病(NDDs)有关的关键靶点,包括乙酰胆碱酯酶、丁酰胆碱酯酶、β-分泌酶、γ-分泌酶、α-突触核蛋白、Aβ 蛋白聚集和神经纤维缠结的形成。与神经递质的生物发生和失活相关的神经信号通路的保守性、遗传操作的简易性和可操作性、成本效益以及短暂的寿命使 elegans 成为神经科学研究和神经退行性疾病高通量药物筛选中最常用的模型之一。在此,我们根据临床试验和流行病学数据对不同黄酮类化合物的神经保护活性进行了批判性评估。这篇综述对各类类黄酮的吸收、代谢和组织分布,以及在分子水平上观察到的神经保护活性的详细机制提供了重要的见解,从而使临床数据合理化。我们进一步扩展了综述范围,对黄酮类化合物在神经退行性疾病治疗中的应用范围进行了批判性评估,并回顾了将秀丽隐杆线虫作为模型生物来研究黄酮类化合物和天然产品的神经保护功效的适宜性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A critical appraisal of geroprotective activities of flavonoids in terms of their bio-accessibility and polypharmacology

A critical appraisal of geroprotective activities of flavonoids in terms of their bio-accessibility and polypharmacology

Flavonoids, a commonly consumed natural product, elicit health-benefits such as antioxidant, anti-inflammatory, antiviral, anti-allergic, hepatoprotective, anti-carcinogenic and neuroprotective activities. Several studies have reported the beneficial role of flavonoids in improving memory, learning, and cognition in clinical settings. Their mechanism of action is mediated through the modulation of multiple signalling cascades. This polypharmacology makes them an attractive natural scaffold for designing and developing new effective therapeutics for complex neurological disorders like Alzheimer's disease and Parkinson's disease. Flavonoids are shown to inhibit crucial targets related to neurodegenerative disorders (NDDs), including acetylcholinesterase, butyrylcholinesterase, β-secretase, γ-secretase, α-synuclein, Aβ protein aggregation and neurofibrillary tangles formation. Conserved neuro-signalling pathways related to neurotransmitter biogenesis and inactivation, ease of genetic manipulation and tractability, cost-effectiveness, and their short lifespan make Caenorhabditis elegans one of the most frequently used models in neuroscience research and high-throughput drug screening for neurodegenerative disorders. Here, we critically appraise the neuroprotective activities of different flavonoids based on clinical trials and epidemiological data. This review provides critical insights into the absorption, metabolism, and tissue distribution of various classes of flavonoids, as well as detailed mechanisms of the observed neuroprotective activities at the molecular level, to rationalize the clinical data. We further extend the review to critically evaluate the scope of flavonoids in the disease management of neurodegenerative disorders and review the suitability of C. elegans as a model organism to study the neuroprotective efficacy of flavonoids and natural products.

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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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