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Agarwal, T, Manandhar, S, B, HK, Famurewa, AC, Gurram, PC, Suggala, RS, Sankhe, R, Mudgal, J and Pai, KSR (2024) Oxyresveratrol-β-cyclodextrin mitigates streptozotocin-induced Alzheimer's model cognitive impairment, histone deacetylase activity in rats: in silico & in vivo studies. Scientific Reports, 14 (1).
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Oxyresveratrolβcyclodextrin mitigates streptozotocin induced Alzheimers model cognitive impairment histone deacetylase activity in rats.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
Alzheimer's disease (AD) is associated with cognitive deficits and epigenetic deacetylation that can be modulated by natural products. The role of natural oxyresveratrol-β-cyclodextrin (ORV) on cognition and histone deacetylase activity in AD is unclear. Herein, in-silico docking and molecular dynamics simulation analysis determined that oxyresveratrol potentially targets histone deacetylase-2 (HDAC2). We therefore evaluated the in vivo ameliorative effect of ORV against cognitive deficit, cerebral and hippocampal expression of HDAC in experimental AD rats. Intracerebroventricular injection of STZ (3 mg/kg) induced experimental AD and the rats were treated with low dose (200 mg/kg), high dose (400 mg/kg) of ORV and donepezil (10 mg/kg) for 21 days. The STZ-induced AD caused cognitive and behavioural deficits demonstrated by considerable increases in acetylcholinesterase activity and escape latency compared to sham control. The levels of malondialdehyde (MDA) and HDAC activity were significantly increased in AD disease group comparison to the sham. Interestingly, the ORV reversed the cognitive-behavioural deficit and prominently reduced the MDA and HDAC levels comparable to the effect of the standard drug, donepezil. The findings suggest anti-AD role of ORV via antioxidant effect and inhibition of HDAC in the hippocampal and frontal cortical area of rats for AD.
| Item Type: | Article |
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| Uncontrolled Keywords: | Hippocampus; Animals; Rats; Rats, Wistar; Alzheimer Disease; Disease Models, Animal; Malondialdehyde; Stilbenes; Streptozocin; beta-Cyclodextrins; Plant Extracts; Male; Molecular Dynamics Simulation; Histone Deacetylase 2; Molecular Docking Simulation; Cognitive Dysfunction; Donepezil; Alzheimer’s disease; Dementia; Epigenetics; In silico docking; Oxyresveratrol; Streptozocin; Animals; Alzheimer Disease; Rats; Streptozocin; Cognitive Dysfunction; Stilbenes; Male; Disease Models, Animal; Histone Deacetylase 2; beta-Cyclodextrins; Molecular Docking Simulation; Hippocampus; Malondialdehyde; Donepezil; Molecular Dynamics Simulation; Rats, Wistar; Plant Extracts; Neurosciences; Behavioral and Social Science; Dementia; Aging; Neurodegenerative; Alzheimer's Disease; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); Brain Disorders; Acquired Cognitive Impairment; 2.1 Biological and endogenous factors; 5.1 Pharmaceuticals; Neurological; Animals; Alzheimer Disease; Rats; Streptozocin; Cognitive Dysfunction; Stilbenes; Male; Disease Models, Animal; Histone Deacetylase 2; beta-Cyclodextrins; Molecular Docking Simulation; Hippocampus; Malondialdehyde; Donepezil; Molecular Dynamics Simulation; Rats, Wistar; Plant Extracts |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General) R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pharmacy and Biomolecular Sciences |
| Publisher: | Nature Research |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 03 Dec 2024 16:41 |
| Last Modified: | 03 Dec 2024 16:45 |
| DOI or ID number: | 10.1038/s41598-024-57188-7 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/24994 |
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