Banu Zeenath, Das Nihar Ranjan
Department of Pharmacology, GITAM School of Pharmacy, GITAM (Deemed to be University), Gandhi Nagar, Rushikonda, Visakhapatnam, Andhra Pradesh, 530045, India.
Department of Pharmacology, RBVRR Women's College of Pharmacy, Barkatpura, Hyderabad, Telangana, 500027, India.
Neurochem Res. 2025 Jul 9;50(4):226. doi: 10.1007/s11064-025-04478-9.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory impairment and cognitive decline. Pathophysiological mechanisms contributing to AD include oxidative stress, increased acetylcholinesterase activity, neuroinflammation, and the accumulation of hyperphosphorylated tau proteins and amyloid-β (Aβ) plaques in the brain. The shortcomings of existing therapeutic approaches have necessitated the exploration of alternative treatment strategies. Elaeocarpus angustifolius Blume, traditionally used for neurological disorders, has been investigated for its neuroprotective potential through its alkaloid-rich fraction. This study evaluated the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of E. angustifolius alkaloid-rich fraction (EAF) and its protective effects against Aβ-induced cytotoxicity in human neuron-like SH-SY5Y cells and murine microglial BV-2 cells using the MTT assay. The results demonstrated that for AChE and BuChE, EAF showed significant inhibition with IC50 of 145.1 ± 4.782 µg/mL and 165.8 ± 1.10 µg/mL, respectively. In the MTT assay, EAF effectively mitigated Aβ-induced cytotoxicity in a dose-dependent manner, with the highest dose (100 µg/mL) restoring viability from 67.91 to 75.31% in SH-SY5Y cells and from 60.29 to 76.01% in BV-2 cells. From these results, it is apparent that EAF has anticholinesterase and neuroprotective properties. However, further research on this may help decipher underlying mechanisms before establishing EAF as an effective alternative in treating AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，主要特征为记忆障碍和认知衰退。导致AD的病理生理机制包括氧化应激、乙酰胆碱酯酶活性增加、神经炎症以及大脑中过度磷酸化的tau蛋白和淀粉样β（Aβ）斑块的积累。现有治疗方法的不足促使人们探索替代治疗策略。狭叶杜英传统上用于治疗神经系统疾病，其富含生物碱的部分已被研究具有神经保护潜力。本研究使用MTT法评估了狭叶杜英富含生物碱部分（EAF）的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制活性及其对人神经元样SH-SY5Y细胞和小鼠小胶质细胞BV-2细胞中Aβ诱导的细胞毒性的保护作用。结果表明，对于AChE和BuChE，EAF表现出显著抑制作用，IC50分别为145.1±4.782μg/mL和165.8±1.10μg/mL。在MTT试验中，EAF以剂量依赖方式有效减轻了Aβ诱导的细胞毒性，最高剂量（100μg/mL）使SH-SY5Y细胞的活力从67.91%恢复到75.31%，使BV-2细胞的活力从60.29%恢复到76.01%。从这些结果可以明显看出，EAF具有抗胆碱酯酶和神经保护特性。然而，对此进行进一步研究可能有助于在将EAF确立为治疗AD的有效替代方法之前，破译其潜在机制。
