Effects of ginger root extract on cognitive impairment and the Nrf2/GPX4/SLC7A11 signaling pathway in aluminum-exposed rats.

Abstract

Aluminum exposure has been widely demonstrated to cause cognitive impairment and neuronal damage, which are significant factors in many neurodegenerative diseases. Ginger root extract (GRE) has attracted researchers' attention in recent years due to its antioxidant and neuroprotective properties, as a potential therapeutic intervention to mitigate aluminum-induced neural damage.To evaluate the effects of GRE on cognitive impairment and the expression of Nrf2, GPX4, and SLC7A11 in aluminum (Al)-exposed rats. In this study, a total of 60 male Sprague-Dawley (SD) rats were randomly assigned to 6 groups: Control, Al exposure (Al), Clinical Drug, low-dose GRE (Al + L-GRE), medium-dose GRE (Al + M-GRE), and high-dose GRE (Al + H-GRE). All groups, except Control, received 10mg/ml AlCl₃ in drinking water for three months. Post-exposure treatments included saline for Control and Al groups, 0.5mg/kg donepezil hydrochloride for the Clinical Drug group, and 100, 200, and 400mg/kg GRE for the respective GRE groups. Treatments were administered once daily, five days a week, for a duration of one month. Cognitive and spatial abilities were assessed using the Morris water maze and Y-maze tests. Neuronal damage and mitochondrial structure in the hippocampus were evaluated via Nissl staining and transmission electron microscopy. Serum levels of SOD, GSH, MDA, and Fe²⁺ were measured, and Nrf2/GPX4/SLC7A11 mRNA and protein levels in hippocampal tissues were analyzed using real-time PCR and Western blotting. The Al group demonstrated compromised cognitive function, diminished neuronal integrity, disrupted mitochondrial structure, and an imbalance in serum antioxidant levels compared to the Control group.GRE treatment appeared to have a positive effect on cognitive function, potentially contributing to the maintenance of neuronal integrity, possibly aiding in the preservation of mitochondrial structure, and potentially assisting in the regulation of antioxidant levels. Notably, the Al + M-GRE and Al + H-GRE groups demonstrated encouraging enhancements in escape latency, platform crossings, novel arm entries, and time spent in the novel arm. Additionally, these groups showed elevated levels of SOD and GSH, reduced levels of MDA and Fe²⁺, and increased expression of Nrf2, GPX4, and SLC7A11, suggesting a potential beneficial impact of GRE treatment.GRE mitigated cognitive impairment in Al-exposed rats, likely through the Nrf2/GPX4/SLC7A11 signaling pathway, demonstrating its potential neuroprotective effects.