Verma Mansi, Mohd Siddique Mohd Usman, Singh Niraj Kumar
Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, NH#19 Delhi Mathura Highway, Chaumuhan, Mathura 281406, UP, India.
Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH#38 Delhi-Roorkee Highway, Meerut-(250005), UP, India.
Curr Top Med Chem. 2025;25(10):1251-1265. doi: 10.2174/0115680266357793241223100307.
Alzheimer's Disease (AD), a prevalent neurodegenerative disorder, poses a significant global health challenge with complicated pathogenesis. Pathological characteristics of AD include increasing loss of cholinergic neurons, oxidative stress, mitochondrial dysfunction, and amyloid beta accumulation. Due to the limited availability of effective therapeutic options with only symptomatic relief and their severe adverse effects, there is a significant need to search and explore new agents for the management of AD. Recently, natural products and/or phytoconstituents of plants have gained notable attention as potential sources of neuroprotective agents due to their diverse chemical constituents, mechanism of action, and relatively safe profiles. In view of this, Glycyrrhiza glabra has been recognized for its several therapeutic properties in traditional medicine systems for centuries. Further, neuroactive phytoconstituents of this plant, including glycyrrhizin, liquiritigenin, isoliquiritigenin, glabridin, and glycyrrhizic acid, exhibit significant pharmacological advantages along with potential neuroprotective effects against AD. and its phytoconstituents have gained significant interest due to its ability to exert a neuroprotective impact by influencing multiple signaling pathways, inhibiting AChE and BACE1 activity, reducing Aβ accumulation, plaque formation, and tau phosphorylation, and quenching the free radical in experimentally-induced AD-like brain. The present review summarizes available and preclinical studies that have been performed to evaluate the beneficial neuroprotective effect of Glycyrrhiza glabra and its phytoconstituents against AD-like pathology. Based on available facts, it can be concluded that neuroactive phytoconstituents of Glycyrrhiza glabra could be significant lead molecules for the drug discovery of anti-AD medicines in the future.
阿尔茨海默病(AD)是一种常见的神经退行性疾病,其发病机制复杂,给全球健康带来了重大挑战。AD的病理特征包括胆碱能神经元的不断丧失、氧化应激、线粒体功能障碍以及β-淀粉样蛋白的积累。由于目前有效的治疗选择有限,仅能缓解症状且副作用严重,因此迫切需要寻找和探索新的药物来治疗AD。近年来,天然产物和/或植物的植物成分因其多样的化学成分、作用机制和相对安全的特性,作为神经保护剂的潜在来源而受到显著关注。鉴于此,甘草在传统医学体系中因其多种治疗特性而被认可了几个世纪。此外,该植物的神经活性植物成分,包括甘草酸、甘草素、异甘草素、光甘草定和甘草次酸,不仅具有显著的药理学优势,还对AD具有潜在的神经保护作用。甘草及其植物成分因其能够通过影响多种信号通路、抑制乙酰胆碱酯酶(AChE)和β-分泌酶1(BACE1)的活性、减少β-淀粉样蛋白(Aβ)的积累、斑块形成和tau蛋白磷酸化,以及清除实验性诱导的AD样大脑中的自由基,从而发挥神经保护作用而备受关注。本综述总结了已进行的评估甘草及其植物成分对AD样病理有益神经保护作用的现有临床前研究。基于现有事实,可以得出结论,甘草的神经活性植物成分可能是未来抗AD药物发现的重要先导分子。