The Effect of Empagliflozin on the Brain Toll Like Receptor-4 Gene Expression in the Experimental Models of Parkinson's Disease

Objective: To investigate the effect of empagliflozin on brain toll like receptor 4 gene expression in animal models of Parkinson and to assess the neuroprotective effect of this intervention Study Design: Experimental studyPlace and Duration of Study: This study was conducted at the Department of Pharmacology, College of Medicine, University of Babylon, Hilla, Iraq from 1st December 2025 to 30th April 2026. Methods: Thirty healthy male albino rats were divided randomly in 5 experimental groups. The time spent on rotarod apparatus was used to assess anti-parkinsonism effect of levodopa/carbidopa and empagliflozin and the real time polymerase chain reaction was used to measure toll like receptor 4 gene expression. Results: Rotenone administration leads to upregulation of toll like receptor 4 gene expression and significant decrease in body weight, also time spent on rotarod apparatus was considerably lower than the control group(p≤0.05) .Conversely, therapeutic intervention with levodopa/carbidopa and empagliflozin in both doses showed a significant increase in locomotor activity and the body weight when compared with group 2. Groups 3, 4 and group 5 demonstrated significant down regulation of toll like receptor 4 gene expression when compared with rotenone group 2. Conclusion: Empagliflozin exhibits promising anti-Parkinsonian like effects and it appears to attenuate the neurodegeneration effect induced by rotenone potentially through down-regulation of toll like receptor 4 in the mid brain tissue.