Neuroprotective evaluation of diospyrin against drug-induced Alzheimer's disease

Fitoterapia. 2023 Dec:171:105703. doi: 10.1016/j.fitote.2023.105703. Epub 2023 Oct 16.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease linked to memory impairment. A current investigation was performed to assess the neuroprotective effect of Diospyrin, a novel therapeutic agent, for the curing of Alzheimer's disease. For this purpose, in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays and antioxidant studies were conducted, whereas in-vivo studies involved different behavioral animal models tests such as elevated plus maze (EPM), morris water maze (MWM) and paddling Y-maze test. Results of the in-vitro analysis showed IC50 values of 95 μg/mL for AChE and 110 μg/mL for BChE as compared to the standard drug donepezil (IC50: 95 & 85 μg/mL, respectively). DPPH antioxidant assay showed a maximum of 72.85% inhibition (IC50: 139.74 μg/mL) of DPPH-free radicals at the highest concentration of 1000 μg/mL as compared to the ascorbic acid (IC50: 13.72 μg/mL). Moreover, the in-vivo analysis revealed that diospyrin treatment demonstrated gradual betterment in memory and enhanced motor functionality. On the other hand, the computational analysis also showed that the diospyrin had exceptional binding affinities for both AChE and BChE enzymes. In the net shell, it may be deduced that our compound diospyrin could be a valuable drug candidate in managing neurodegenerative disorders like AD.

Keywords: Alzheimer's disease; Cholinesterase inhibition antioxidant activity; Diospyrin; Neuroprotection.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Acetylcholinesterase / therapeutic use
  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / drug therapy
  • Animals
  • Antioxidants / chemistry
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism
  • Butyrylcholinesterase / therapeutic use
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Molecular Docking Simulation
  • Molecular Structure
  • Neurodegenerative Diseases*
  • Neuroprotective Agents* / pharmacology

Substances

  • Butyrylcholinesterase
  • Antioxidants
  • Acetylcholinesterase
  • Cholinesterase Inhibitors
  • diospyrin
  • Neuroprotective Agents