Neuroprotective effects of linagliptin in a rotenone-induced rat model of Parkinson's disease.

The present study investigates the antiParkinsonian activity of dipeptidyl peptidase-4 (DPP-IV) inhibitor, linagliptin. The experimental Parkinson's disease (PD) was induced by administration of rotenone at a dose of 1.5 mg/kg at alternate day subcutaneously for 21 days. Standard drug (levodopa-200 mg/kg and carbidopa-50 mg/kg) and treatment drug (linagliptin-5 mg/kg, 10 mg/kg, and 20mg/kg) were administered orally daily 1 h before rotenone administration. In a rat rotenone model, linagliptin improved muscle coordination, motor performance, and corrected akinesia. Pretreatment with linagliptin showed significant higher levels of superoxide dismutase, catalase, and glutathione in brain homogenate of animals. Linagliptin significantly elevated the levels of striatal DA and active glucagon-like peptide 1 in brain homogenate of animals. Furthermore, linagliptin amended alterations induced by rotenone in the thiobarbituric acid reactive substances and inflammatory marker such as tumor necrosis factor-α level. The results of the present study indicate the neuroprotective potential of linagliptin for the management of PD might be due to remarkable improvement in motor functions, antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective mechanisms.