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阿尔茨海默病的病理生理机制及其植物天然产物治疗的深入了解。

An Insight in Pathophysiological Mechanism of Alzheimer's Disease and its Management Using Plant Natural Products.

机构信息

Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221005, India.

出版信息

Mini Rev Med Chem. 2021;21(1):35-57. doi: 10.2174/1389557520666200730155928.

Abstract

Alzheimer's disease (AD) is an age-associated nervous system disorder and a leading cause of dementia worldwide. Clinically, it is described by cognitive impairment and pathophysiologically by deposition of amyloid plaques and neurofibrillary tangles in the brain and neurodegeneration. This article reviews the pathophysiology, course of neuronal degeneration, and the various possible hypothesis of AD progression. These hypotheses include amyloid cascade, tau hyperphosphorylation, cholinergic disruption, metal dysregulation, vascular dysfunction, oxidative stress, and neuroinflammation. There is an exponential increase in the occurrence of AD in the recent few years that indicate an urgent need to develop some effective treatment. Currently, only 2 classes of drugs are available for AD treatment, namely acetylcholinesterase inhibitor and NMDA receptor antagonist. Since AD is a complex neurological disorder and these drugs use a single target approach, alternatives are needed due to limited effectiveness and unpleasant side-effects of these drugs. Currently, plants have been used for drug development research especially because of their multiple sites of action and fewer side effects. Uses of some herbs and phytoconstituents for the management of neuronal disorders like AD have been documented in this article. Phytochemical screening of these plants shows the presence of many beneficial constituents like flavonoids, triterpenes, alkaloids, sterols, polyphenols, and tannins. These compounds show a wide array of pharmacological activities, such as anti-amyloidogenic, anticholinesterase, and antioxidants. This article summarizes the present understanding of AD progression and gathers biochemical evidence from various works on natural products that can be useful in the management of this disease.

摘要

阿尔茨海默病(AD)是一种与年龄相关的神经系统疾病,也是全球痴呆症的主要病因。临床上,它表现为认知障碍,病理上表现为大脑中淀粉样斑块和神经原纤维缠结的沉积和神经退行性变。本文综述了 AD 的病理生理学、神经元退行性变过程和 AD 进展的各种可能假说。这些假说包括淀粉样蛋白级联、tau 过度磷酸化、胆碱能破坏、金属失调、血管功能障碍、氧化应激和神经炎症。近年来,AD 的发病率呈指数级增长,这表明迫切需要开发一些有效的治疗方法。目前,只有 2 类药物可用于 AD 的治疗,即乙酰胆碱酯酶抑制剂和 NMDA 受体拮抗剂。由于 AD 是一种复杂的神经退行性疾病,这些药物采用单一靶点方法,由于这些药物的疗效有限且副作用令人不快,因此需要替代药物。目前,植物已被用于药物开发研究,特别是因为它们具有多种作用部位和较少的副作用。本文记录了一些草药和植物成分用于管理 AD 等神经元疾病的用途。这些植物的植物化学筛选表明存在许多有益的成分,如类黄酮、三萜、生物碱、甾醇、多酚和单宁。这些化合物表现出广泛的药理活性,如抗淀粉样形成、抗胆碱酯酶和抗氧化作用。本文总结了 AD 进展的现有认识,并从各种天然产物的工作中收集了生化证据,这些证据可能对这种疾病的管理有用。

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