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Attenuation of Scopolamine-Induced Amnesia via Cholinergic Modulation in Mice by Synthetic Curcumin Analogs
Authors:Haya Hussain  Shujaat Ahmad  Syed Wadood Ali Shah  Abid Ullah  Niaz Ali  Mazen Almehmadi  Manzoor Ahmad  Atif Ali Khan Khalil  Syed Babar Jamal  Hanif Ahmad  Mustafa Halawi
Abstract:Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a–1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.
Keywords:curcumin analogs  Alzheimer’  s disease  amnesia  acetylcholinesterase  butyrylcholinesterase  docking  scopolamine  EPM  Y-maze  NORT  hippocampus
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