Cyclopentanone Derivative Attenuates Memory Impairment by Inhibiting Amyloid Plaques Formation in the 5xFAD Mice

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder. This study was designed to investigate the effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) on behavior, amyloid β (Aβ) plaque deposition, and βAPP cleaving enzyme-1 (BACE-1) expression in the 5xFAD mouse brain. In this study, computational studies were conducted to predict the binding mode of the 3NCP with target sites of the β-secretase. In vivo studies were performed on the 5xFAD mice model of AD using different behavioral test models like light/dark box, elevated plus maze (EPM), and the Barnes maze tests for the assessment of anxiety, spatial learning and memory. The thioflavin-S staining, immunohistochemistry (IHC), and RT-PCR studies were carried out to find the effect of the 3NCP on the β-amyloid plaques formation and BACE-1 expression. The results of the computational studies showed that the 3NCP has excellent binding affinities for beta-secretase. The light/dark box study depicted that the 3NCP does not cause anxiety. The 3NCP treatment effects in the EPM and Barnes maze tests showed a significant effect on learning and memory. Furthermore, the results of the thioflavin staining and IHC revealed that the 3NCP significantly reduced the formation of the beta-amyloid plaques in brain tissues. Moreover, the RT-PCR study showed that 3NCP significantly reduced the BACE-1 expression in the brain. Conclusively, the results of the current study demonstrate that the 3NCP may be a potential candidate for AD treatment in the future.

The Neuroprotective Propensity of Organic Extracts of Acacia stenophylla Bark and Their Effectiveness Against Scopolamine-/Diazepam-Induced Amnesia in Mice

“…The Acacia stenophylla bark contains cyclic ketone derivatives, it has been reported that these derivatives reduce cholinesterases activities, Aβ plaques formation, neuroinflammation, and oxidative stress in the mice model of Alzheimer's disease. 30,72 The possible mechanism of action of Acacia stenophylla bark extracts to ameliorate amnesia is their anti-cholinesterase and anti-oxidant activities and the anti-inflammatory, anti-oxidant, and anti-cholinesterase properties of their active constituents derivatives. The schematic representation of ASEE and ASB extracts is shown in Figure 9.…”