Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new anti-AD remedies, 2-[Hydroxy-(4-nitrophenyl)methyl]-cyclopentanone (NMC), a β hydroxyl ketone derivative was studied to explore its neuroprotective potentials against AD. The in-vitro AChE and BuChE enzymes inhibition were evaluated by Ellman protocol and antioxidant potentials of NMC by DPPH free radical scavenging assay. In-vivo behavioral studies were performed in the transgenic 5xFAD mice model of AD using shallow water maze (SWM), Paddling Y-Maze (PYM), elevated plus maze (EPM) and balance beam (BB) tests. Also, the ex-vivo cholinesterase inhibitory effects of NMC and histopathological analysis of amyloid-β plaques were determined in the frontal cortex and hippocampal regions of the mice brain. NMC exhibited significant in vitro anti-cholinesterase enzyme potentials with an IC₅₀ value of 67 μg/ml against AChE and 96 μg/ml against BuChE respectively. Interestingly, the activities of AChE and BuChE enzymes were also significantly lower in the cortex and hippocampus of NMC-treated groups. Also, in the DPPH assessment, NMC displayed substantial antioxidant properties with an IC₅₀ value observed as 171 μg/ml. Moreover, histopathological analysis via thioflavin-s staining displayed significantly lower plaques depositions in the cortex and hippocampus region of NMC-treated mice groups. Furthermore, SWM, PYM, EPM, and BB behavioral analysis indicated that NMC enhanced spatial learning, memory consolidation and improved balance performance. Altogether, to the best of our knowledge, we believe that NMC may serve as a potential and promising anti-cholinesterase, antioxidant and neuroprotective agent against AD.

阿尔茨海默氏病（AD）是一种进行性，慢性和与年龄相关的神经退行性疾病，影响了全球成千上万人。为了追求新的抗AD疗法，研究了β-羟基酮衍生物2- [羟基-（4-硝基苯基）甲基]-环戊酮（NMC），以探索其抗AD的神经保护潜力。通过Ellman方案评估了体外AChE和BuChE酶的抑制作用，并通过DPPH自由基清除试验评估了NMC的抗氧化能力。使用浅水迷宫（SWM），划桨Y型迷宫（PYM），高架迷宫（EPM）和平衡木（BB）测试在转基因5xFAD小鼠AD模型中进行体内行为研究。也，在小鼠大脑的额叶皮层和海马区测定了NMC的离体胆碱酯酶抑制作用和淀粉样β蛋白斑的组织病理学分析。NMC通过IC表现出显着的体外抗胆碱酯酶潜力针对AChE的₅₀值分别为67μg/ ml和针对BuChE的96μg/ ml。有趣的是，在NMC处理组的皮质和海马中，AChE和BuChE酶的活性也显着降低。另外，在DPPH评估中，NMC的IC ₅₀表现出显着的抗氧化性能观察到的值为171μg/ ml。此外，通过硫代黄素-s染色的组织病理学分析显示，在NMC处理的小鼠组的皮质和海马区中，斑块的沉积明显降低。此外，SWM，PYM，EPM和BB行为分析表明NMC增强了空间学习，记忆巩固并改善了平衡表现。总之，据我们所知，我们相信NMC可以作为潜在且有前途的抗胆碱酯酶，抗氧化剂和抗AD的神经保护剂。