Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting the elderly, characterized by mitochondrial dysfunction. Mitochondria play a dual role in AD, serving both as the main source of reactive oxygen species (ROS) generation and as a major target of oxidative damage. This study aimed to investigate the protective mechanisms of ellagic acid (EA) a natural dietary polyphenol on mitochondrial function in an intracerebroventricular (ICV) streptozotocin (STZ)-injected rat model of AD. Rats were randomly assigned to six groups: Control, Sham, STZ (1.5 mg/kg on days 1 and 3), STZ + EA 5 mg/kg, STZ + EA 50 mg/kg, and STZ + EA 100 mg/kg. On day 14, behavioral tests (Shuttle box and Step-down), histopathological evaluations, oxidative stress markers, and mitochondrial indices were assessed in brain tissue. Treatment with EA (100 mg/kg) significantly improved spatial memory, as evidenced by increased latency time in the Morris water maze test (p < 0.001). Furthermore, EA treatment mitigated hippocampal neurodegeneration, increasing neuronal density in the CA1 subfield (p < 0.001) and restoring total hippocampal volume (p < 0.01). At the biochemical level, EA markedly reduced oxidative stress levels (p < 0.001) and enhanced mitochondrial function, restoring cortical ATP levels (p < 0.001) and cytochrome c oxidase activity (p < 0.01) compared to the STZ- group. In conclusion, these findings suggest that EA may have therapeutic potential in mitigating mitochondrial dysfunction and oxidative stress in AD, offering a promising approach for addressing neurodegeneration and energy deficits associated with the disease.