A Novel Nanoformulation of Ellagic Acid is Promising in Restoring Oxidative Homeostasis in Rat Brains with Alzheimer's Disease

Abstract

Background: Aluminum toxicity induces neurodegenerative changes in the brain and results in Alzheimer's disease (AD).

Objective: Here, the aim was to evaluate the antioxidant therapeutic effects of ellagic acid (EA) and EA-loaded nanoparticles (EA-NP) in an aluminum chloride-induced AD rat model.

Methods: The nanoparticles' loading of EA was 0.84/1 w/w. The in vitro release kinetics of EA from EA-NP in fetal bovine serum showed 60% release in the first 1-5 hours, followed by sustained release at 60-70% over 6-24 hours. Six groups were implemented; group 1 served as the control, group 2 received EA, group 3 received EA-NP, group 4 was the AD rat model administered AlCl3 (50 mg/kg) for 4 weeks, groups 5 (AD+EA) and 6 (AD+EA-NP) were treated with EA and EA-NP, respectively, for 2 weeks after AlCl3 was stopped. The neurotoxicity in the rat brain was examined by measuring the brain antioxidant biomarkers catalase, glutathione, and total antioxidant activity and lipid peroxidation (thiobarbituric acid, TBA). Histopathological studies using hematoxylin and eosin, cresyl violet, silver stains, and the novel object recognition test were examined.

Results: Data revealed significant increase of antioxidant biomarkers and decreased TBA in the EA-NP group. The pathological hallmarks of AD-vacuolation of the neurons, chromatolysis, neurofibrillary tangles, and the senile plaques in brains of the AD rat model were decreased and restoration of Nissl granules was noted. The calculated discrimination index in the behavioral test increased more in cases treated with EA-NP.

Conclusion: The treatment of AD with EA-NP was more effective than EA in alleviating the oxidative neurotoxic effects on AD rat brains.

Keywords: Alzheimer`s disease; aluminum; antioxidant biomarkers; ellagic acid; nano-ellagic acid; nanoformulation; neuroprotection.; oxidative stress.