Alyami Bandar A, Ahmad Zeeshan, Ghufran Mehreen, Mahnashi Mater H, Sadiq Abdul, Ayaz Muhammad
Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Kingdom of Saudi Arabia.
Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), KP, Pakistan.
Curr Neuropharmacol. 2025;23(3):317-328. doi: 10.2174/1570159X22666240329125626.
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.
Standard protocols were followed in the 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.
In DPPH and ABTS assays, isoeugenol exhibited considerable efficacy against free radicals with IC 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 the BChE enzyme via two arene-hydrogen interactions and one hydrogen bond.
Isoeugenol offered considerable protection against scopolamine-induced memory deficits and improved the special memory of the rodents.
阿尔茨海默病（AD）是一种影响老年人群的神经退行性疾病，与行为不稳定和认知衰退有关。目前仅有少数药物被批准用于AD的临床治疗。挥发油及其成分具有多种药理潜力，包括神经保护特性。本研究旨在评估异丁香酚对东莨菪碱引起的认知障碍的神经保护潜力。
抗氧化、胆碱酯酶抑制和分子对接实验均遵循标准方案。最初使用DPPH和ABTS自由基清除实验评估异丁香酚的抗氧化潜力。随后，按照埃尔曼实验进行乙酰胆碱酯酶/丁酰胆碱酯酶抑制研究。为评估该化合物在酶靶点部位的结合有效性，将其与胆碱酯酶的结合位点进行对接。使用浅水迷宫（SWM）、Y迷宫和高架十字迷宫（EPM）实验评估异丁香酚补充剂对东莨菪碱诱导的失忆的影响。
在DPPH和ABTS实验中，异丁香酚对自由基表现出显著效果，其IC50分别为38.97和43.76μg/mL。在1mg/ml浓度下，异丁香酚对乙酰胆碱酯酶和丁酰胆碱酯酶的抑制率分别为78.39±0.40%和67.73±0.03%。在对接研究中，异丁香酚的对接分数为-12.2390，在乙酰胆碱酯酶的活性位点残基处形成两个氢键。此外，异丁香酚以-10.1632的对接分数通过两个芳烃-氢相互作用和一个氢键与丁酰胆碱酯酶充分结合。
异丁香酚对东莨菪碱诱导的记忆缺陷提供了显著保护，并改善了啮齿动物的空间记忆。
