In Silico Study and Pharmacological Evaluation of Eplerinone as an Anti-Alzheimer's Drug in STZ-Induced Alzheimer's Disease Model.

Abstract

Alzheimer’s disease (AD) is the neurodegenerative disorder characterized by impairment of higher intellectual dysfunctions associated with changes in the cognitive, behavioral, and social activities. Aim of the study: The current study was designed to evaluate the potential of aldosterone antagonist in the treatment of AD. Methodology: The study was conducted on albino mice of either sex (n = 60). Mice were subcategorized into six groups, each group having 10 mice. Group I—normal control (CMC 1 mL/kg), group II—diseased [streptozotocin (STZ), 3 mg/kg, intracerebroventricular (i.c.v.)], group III—standard (piracetam, 200 mg/kg, i.p.), and groups IV–VI designated as the treatment group (eplerinone at dose levels of 4, 8, and 16 mg/kg, orally), respectively. The study was carried out for 14 consecutive days. STZ was administered through the i.c.v. route on first and third days of the study for memory impairment. The molecular docking was performed to investigate the chemical behavior of compounds to inhibit the AChE. Anti-Alzheimer’s effect was assessed by using the behavioral paradigms such as passive avoidance, elevated plus maze, Morris water maze, open field, and balance beam. Various endogenous antioxidants such as SOD, GSH, nitrite, MDA, CAT, and AChE were identified in brain tissues of treated mice to assess the oxidative stress index. Biochemical markers for AD such as norepinephrine, dopamine, and serotonin, Aβ 1–40, Aβ 1–42, NF-κB, and tumor necrosis factor alpha were analyzed in brain tissues of mice. Expression of beta amyloid was observed by PCR. Results: The in silico study indicated the distinct mechanism of eplerinone to inhibit the AChE. The outcomes of the in vivo study manifested that eplerinone at the highest dose was found to be more effective in the treatment of AD. Conclusion: It may be concluded from the research work that eplerinone can be effective for cognitive improvement which proposes its therapeutic effect in many neurodegenerative disorders such as AD.