Epalrestat improves motor symptoms by reducing oxidativestress and inflammation in the reserpine induced mouse model of Parkinson's disease

摘要

Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but improve the quality of life.Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis.Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS.Therefore,in this study,we investigated the role of Epalrestat in the reserpine induced mouse model of PD.Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia,muscular rigidity,palpebral ptosis,and tremor,as well as conducting swim and open field tests.Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.Results:Epalrestat treatment significantly improved akinesia and bradykinesia,muscular dysfunctions,tremor level,and gait functions compared to the reserpine group.It also improved the latency in the swim test.Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes,glutathione,catalase,and superoxide dismutase.Furthermore,Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.