Appraisal of the Neuroprotective Potentials of Isoeugenol Using In-vitro, In-vivo and In-silico Approaches

Background: Alzheimer's disease (AD) is a neurodegenerative condition that affects the elder population and is linked to behavioral instability and cognitive decline. Only a few drugs are approved for clinical management of AD. Volatile oils and their components exhibit diverse pharmacological potentials, including neuroprotective properties. The current study aimed to evaluate isoeugenol's neuroprotective potentials against cognitive impairments caused by scopolamine. Methods: Standard protocols were followed in the in-vitro antioxidant, cholinesterase inhibitory and molecular docking assays. Isoeugenol was initially evaluated for antioxidant potential using DPPH and ABTS free radicals scavenging assays. Subsequently, AChE/BChE inhibition studies were performed following Ellman’s assay. To assess the compound's binding effectiveness at the enzymes' target site, it was docked against the binding sites of cholinesterase. The effect of isoeugenol supplementation on scopolamine-induced amnesia was assessed using Shallow Water Maze (SWM), Y-Maze and Elevated Plus Maze (EPM) tests. Results: In DPPH and ABTS assays, isoeugenol exhibited considerable efficacy against free radicals with IC50 of 38.97 and 43.76 μg/mL, respectively. Isoeugenol revealed 78.39 ± 0.40% and 67.73 ± 0.03% inhibitions against AChE and BChE, respectively, at 1 mg/ml concentration. In docking studies, isoeugenol exhibited a docking score of -12.2390, forming two hydrogen bonds at the active site residues of AChE. Further, with a docking score of -10.1632, isoeugenol binds adequately to theBChE enzyme via two arene-hydrogen interactions and one hydrogen bond. Conclusion: Isoeugenol offered considerable protection against scopolamine-induced memory deficits and improved the special memory of the rodents.