Investigating new drugs or formulations that target Alzheimer disease (AD) is critical for advancing therapeutic interventions. Therefore, this study aimed to assess the effectiveness of nanoencapsulated curcumin (NC Curc) in alleviating memory impairment, oxidative stress, and neuroinflammation in a validated AD model. Male Wistar rats were given bilateral intracerebroventricular injections of either saline or streptozotocin (STZ) (3 mg/3 µL/site) to establish the AD model (day 0). On day 22, daily oral administrations of curcumin (6 mg/kg), NC Curc (6 mg/kg), or a vehicle (unloaded NC) were initiated and continued for 14 days. NC Curc significantly reversed memory deficits in object recognition and inhibitory avoidance tests induced by STZ. Both formulations of curcumin attenuated elevated acetylcholinesterase activity caused by STZ. Importantly, NC Curc alone effectively mitigated STZ-induced oxidative stress. Additionally, NC Curc treatment normalized GFAP levels, suggesting a potential reduction in neuroinflammation in STZ-treated rats. Our findings indicate that NC Curc improves memory in an AD rat model, highlighting its enhanced therapeutic effects compared to unencapsulated curcumin. This research significantly contributes to understanding the therapeutic and neurorestorative potential of NC Curc in AD, particularly in reversing pathophysiological changes.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder marked by motor deficits and non-motor symptoms, such as depression, which are associated with dopaminergic loss and α-synuclein aggregation in the brain. Objectives: This study investigated the neuroprotective effects of a hydroalcoholic extract of the purple fruit of Eugenia uniflora (PFEU) on motor ability and depressive-like behaviors in a PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in female Wistar rats. Methods: Rats received intranasal administration of MPTP or vehicle, followed by 14 days of oral administration of PFEU (300 or 2000 mg/kg, administered once daily) or vehicle. Depressive-like behavior was assessed using the splash and forced swimming tests, while motor ability was evaluated using the rotarod and open field tests. On day 15, hippocampal tissue was collected for immunoreactivity analysis. Results: MPTP treatment induced depressive-like behavior, which was significantly reversed by PFEU, as evidenced by increased grooming and decreased immobility. No motor coordination or locomotion deficits were observed. Furthermore, PFEU treatment prevented the MPTP-induced increase in hippocampal α-synuclein, p-p53, and Bax while restoring Bcl-2 levels, suggesting neuroprotective effects through the modulation of apoptotic pathways and α-synuclein. Conclusions: These findings support PFEU’s potential as a neuroprotective agent for MPTP-induced depressive-like behavior in female rats, highlighting its molecular mechanisms.

Alzheimer's disease (AD) is characterized by cognitive impairment and neuropsychiatric disturbances, including depression, both tightly linked to redox imbalance and neuroinflammatory activation. This study investigated whether the selenium-containing compound 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) mitigates behavioral and biochemical alterations in a β-amyloid (Aβ)-induced mouse model of AD through modulation of redox-regulated pathways. Male Swiss mice received intracerebroventricular Aβ (25-35) or saline (3 µL/site) and were treated orally for seven days with 4-PSQ (1 mg/kg), paroxetine (1 mg/kg), or donepezil (1 mg/kg). Depressive-like behavior and memory performance were assessed, followed by determination of plasma corticosterone, reactive species levels, lipid peroxidation, antioxidant enzyme activities, neuroinflammatory mediators, and acetylcholinesterase (AChE) activity in the hippocampus and prefrontal cortex of mice. 4-PSQ significantly reversed Aβ-induced depressive behavior and memory impairment. The compound normalized plasma corticosterone levels, reduced reactive species and lipid peroxidation, and restored antioxidant enzyme activity. It also decreased the expression of inflammatory markers while regulating AChE activity, indicating concomitant modulation of redox, neuroimmune, and cholinergic pathways. By restoring redox homeostasis and attenuating neuroinflammatory responses, 4-PSQ effectively counteracted behavioral and biochemical disruptions associated with Aβ toxicity. These findings support 4-PSQ as a promising selenium-based therapeutic candidate targeting redox-driven features of AD, including comorbid depression and cognitive decline.