帕金森病(PD)是仅次于阿尔茨海默病的第二大最常见的神经系统疾病,主要影响老年人口,严重影响他们的生活质量。PD的确切病因仍然难以捉摸,但是最近的研究揭示了潜在的因素,包括α-突触核蛋白聚集体的形成,氧化应激,神经递质失衡,和大脑黑质致密部(SNpc)区域的多巴胺能神经变性,最终导致运动症状,如运动迟缓,运动障碍,震颤,和刚性。单胺氧化酶(MAO)是一种必需的酶,包含两种同工型,MAO-A和MAO-B,负责氧化单胺,如多巴胺。MAO-B活性的增加是中脑SNpc区域多巴胺水平降低的原因,这与PD样表现的发病机理显着相关。MAO-B抑制剂增强纹状体神经元对多巴胺的反应,使它们在治疗PD中有价值,涉及多巴胺缺乏。临床批准的MAO-B抑制剂如司来吉兰,L-异戊二烯,Pargyline,和雷沙吉兰用于治疗与PD相关的神经退行性疾病。包括用于PD的MAO-B抑制剂在内的当前治疗性干预主要旨在缓解这些运动症状,但通常伴随着许多副作用,这对于患者而言可能是特别具有挑战性的。虽然有效,他们有局限性,促使人们寻找替代疗法,人们对探索天然产物(特别是类黄酮)作为新型MAO-B抑制剂的潜在来源的兴趣与日俱增。与此相符,本综述的重点是植物来源的天然黄酮类化合物,有望成为新型MAO-B抑制剂的潜在候选化合物。讨论包括体外和体内研究,阐明其潜在的治疗应用。此外,这篇综述强调了探索天然产物作为MAO-B抑制剂有价值的储库的重要性,为药物开发提供了新的途径,并解决了对改善PD样病理状况的治疗的迫切需要。这篇综述的作者主要探讨了具有显着MAO-B抑制活性的天然黄酮类化合物的神经保护潜力,以及在PD治疗中的多靶向方法,临床证据和当前治疗方法面临的挑战。
Parkinson\'s disease (PD) stands as the second most common neurological disorder after Alzheimer\'s disease, primarily affecting the elderly population and significantly compromising their quality of life. The precise etiology of PD remains elusive, but recent research has shed light on potential factors, including the formation of α-synuclein aggregates, oxidative stress, neurotransmitter imbalances, and dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) region of the brain, culminating in motor symptoms such as bradykinesia, akinesia, tremors, and rigidity. Monoamine oxidase (MAO) is an essential enzyme, comprising two isoforms, MAO-A and MAO-B, responsible for the oxidation of monoamines such as dopamine. Increased MAO-B activity is responsible for decreased dopamine levels in the SNpc region of mid brain which is remarkably associated with the pathogenesis of PD-like manifestations. Inhibitors of MAO-B enhance striatal neuronal responses to dopamine, making them valuable in treating PD, which involves dopamine deficiency. Clinically approved MAO-B inhibitors such as selegiline, L-deprenyl, pargyline, and rasagiline are employed in the management of neurodegenerative conditions associated with PD. Current therapeutic interventions including MAO-B inhibitors for PD predominantly aim to alleviate these motor symptoms but often come with a host of side effects that can be particularly challenging for the patients. While effective, they have limitations, prompting a search for alternative treatments, there is a growing interest in exploring natural products notably flavonoids as potential sources of novel MAO-B inhibitors. In line with that, the present review focuses on natural flavonoids of plant origin that hold promise as potential candidates for the development of novel MAO-B inhibitors. The discussion encompasses both in vitro and in vivo studies, shedding light on their potential therapeutic applications. Furthermore, this review underscores the significance of exploring natural products as valuable reservoirs of MAO-B inhibitors, offering new avenues for drug development and addressing the pressing need for improved treatments in PD-like pathological conditions. The authors of this review majorly explore the neuroprotective potential of natural flavonoids exhibiting notable MAO-B inhibitory activity and additionally multi-targeted approaches in the treatment of PD with clinical evidence and challenges faced in current therapeutic approaches.