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


Steve Harakeh*, Mohamad H. Qari, Wafaa S. Ramadan, Soad K. Al Jaouni, Mohammed S. Al Muhayawi, Turki Al Amri, Ghulam Md Ashraf, Dhruba J Bharali and Shaker A Mousa*   Pages 1 - 9 ( 9 )


Background: Aluminum toxicity induces neurodegenerative changes in 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 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 AD rat model were decreased and restoration of Nissl granules was noted. The calculated discrimination index in 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 in AD rat brains.


Alzheimer’s disease, aluminum, oxidative stress, antioxidant biomarkers, ellagic acid, nanoformulation, nano-Ellagic acid, neuroprotection.


Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University (KAU), Department of Hematology, King Abdulaziz University (KAU), Jeddah, Department of Anatomy, Faculty of Medicine, KAU, Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, KAU, Department of Medical Microbiology/Parasitology and Molecular Microbiology Laboratory, KAUH, KAU, Family and Community Medicine Department, Faculty of Medicine-Rabigh Branch, King Abdulaziz University, Jeddah, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Albany Nutraceuticals, Rensselaer, NY, 12144, Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University (KAU)

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