Center for Innovation in Molecular and Pharmaceutical Sciences (CIMPS), Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, 500046, India.
Amity Institute of Biotechnology, Amity University, Kolkata, 700135, India.
Neurochem Int. 2024 Nov;180:105859. doi: 10.1016/j.neuint.2024.105859. Epub 2024 Sep 10.
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.
类黄酮是一种常见的天然产物，具有抗氧化、抗炎、抗病毒、抗过敏、保肝、抗癌和神经保护等多种健康益处。有几项研究报告称，类黄酮在改善临床记忆、学习和认知方面具有有益作用。它们的作用机制是通过调节多种信号级联来实现的。这种多效性使它们成为设计和开发新的有效治疗复杂神经退行性疾病（如阿尔茨海默病和帕金森病）的有吸引力的天然支架。类黄酮被证明可以抑制与神经退行性疾病相关的关键靶点，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 蛋白聚集和神经原纤维缠结形成。与神经递质生物合成和失活、遗传操作和可操作性、成本效益相关的保守神经信号通路，以及它们的短寿命，使秀丽隐杆线虫成为神经科学研究和高通量药物筛选中最常用的模型之一，用于神经退行性疾病。在这里，我们根据临床试验和流行病学数据，批判性地评估了不同类黄酮的神经保护活性。这篇综述提供了关于各种类黄酮的吸收、代谢和组织分布的关键见解，以及在分子水平上观察到的神经保护活性的详细机制，以合理化临床数据。我们进一步扩展了综述，批判性地评估了类黄酮在神经退行性疾病管理中的范围，并回顾了秀丽隐杆线虫作为研究类黄酮和天然产物神经保护功效的模型生物的适宜性。
