Abstract:
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.
