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.

Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

“…E Extinction coefficient of hydrogen peroxide (0.071 mmol/cm). Protein contents were estimated using the Lowry's method (Hira et al, 2020).…”

Appraisal of anti‐Parkinson activity of rhinacanthin‐C in haloperidol‐induced parkinsonism in mice: A mechanistic approach

“…After that, it was placed in an ice bath, and then, centrifuged for 10 min at 3000 rpm. The upper layer was obtained to measure absorbance at 532 nm (Hira et al, 2020). The MDA will be calculated by using following formula:…”

“…After cooling to room temperature, absorbance was measured at 352 and 452 nm for dopamine and noradrenaline, respectively. Blank for dopamine and noradrenaline was prepared in reverse order, that is, Na 2 SO 3 before iodine (Hira et al, 2020).…”

“…On testing day, time to complete the walk on apparatus was recorded. The maximum time allowed per mice was 180 s (Hira et al, 2020).…”

“…The aqueous phase of brain tissue was prepared according to the earlier method (Hira et al, 2020). For serotonin analysis, 0.25 ml of o-phthaldialdehyde was added to 0.2 ml of the aqueous phase and heated to 100°C for 10 min.…”