Effect of thymol on oxidative stress and reelin signaling pathway in Alzheimer's disease model

The purpose of this study was to investigate how thymol affects cognitive functions and the levels of MDA, GSH, Aβ_1-42, ApoE, reelin, and LRP8 in an AD model induced in male Wistar albino rats with the application of D-galactose (D-gal) and aluminum chloride (AlCl₃).

In this work, 3-month-old male Wistar albino rats were used. Group 1 served as the Control, Group 2 received 0.5 mL/day saline + 0.5 mL/day sunflower oil, Group 3 was administered 200 mg/kg/day AlCl₃ + 60 mg/kg/day D-gal, Group 4 received 30 mg/kg/day thymol, and Group 5 was administered 200 mg/kg/day AlCl₃ + 60 mg/kg/day D-gal + 30 mg/kg/day thymol. At the end of the 10-week experimental period, behavioral and memory tests were performed. GSH and MDA levels were measured in the obtained serum and brain tissue samples, while Aβ_1-42, ApoE, reelin, and LRP8 levels were measured in brain tissue samples. Statistical analyses were performed using ANOVA test in Graphpad Prism V8.3 program. A p-value <0.05 was considered significant in intergroup analyses.

When the novel object recognition test (NORT) results were evaluated, the Alzheimer + thymol (ALZ+TYM) group showed a significant increase in the recognition index (RI) and discrimination index (DI) compared to the Alzheimer (ALZ) group at the 24th hour. Thymol reduced working memory errors (WME), reference memory errors (RME), and maze completion time at 48, 72, and 96 hours when evaluated in terms of spatial memory in rats with Alzheimer's disease. Furthermore, Aβ_1-42 and ApoE levels were increased in the ALZ group compared to the control (C), while reelin and LRP8 levels were decreased in the ALZ group compared to the C group.

The data we obtained suggest that thymol may play an effective role in cognitive processes against AD and have an anti-Alzheimer's disease effect.