ResArginTM, a conjugate of resveratrol and arginine, prevents memory impairment and oxidative stress in the Alzheimer’s disease rat model intoxicated with aluminum chloride

Background: Effective drugs for the prevention and treatment of Alzheimer's disease (AD) remain scarce. Antioxidant compounds are increasingly being explored for their anti-Alzheimer’s potential. This has led to the inclusion of up to three compounds in the 2023 Alzheimer's drug development pipeline for phase 3 trials targeting oxidative stress. This study presents the antioxidant effects of ResArginTM (a conjugate of resveratrol and the amino acid arginine) and its protective effects against memory loss in a rat model of AD induced by AlCl3. Method: Female rats were given AlCl3 (50mg/kg bw) by oral gavage, except for the normal control group. One hour later, they were given distilled water for the positive control, 300 and 500 mg/kg b.w ResArginTM for the test groups, or 1 mg/kg b.w Donepezil (reference 1) or 100mg/kg for vitamin E (reference 2) by daily gavage for 42 days. Neurobehavioral tests (Elevated Plus Maze and Morris Water Maze) were performed. Subsequently, the rats were sacrificed and the levels of MDA and GSH in rat brains were measured. The activity of antioxidant enzymes (SOD, CAT, GPx) and the level of reduced glutathione (GSH) were assessed in the rat brain. Histological sections of the regions of the hippocampus were made. Results: ResArginTM (300mg/kgbw and 500 mg/kgbw) treatments preserved the learning profile and reduced latency time to reach the target quadrant in the MWM. ResArginTM at 500mg/kg b.w (RSA500) significantly reduced (p < 0.05) the latency time to reach the target quadrant from 5.0 ± 1.01 seconds at week 2 to 2.3 ± 0.4 seconds at week 6. They protected the different areas of the brain (CA1, 3, and DG) from alterations induced by AlCl3 and prevented oxidative stress in the brain. Conclusion: ResArginTM prevents memory disorders, memory loss, altered hippocampus areas, and oxidative stress induced by AlCl3 in rats.