Fisetin Ameliorates Levodopa-Induced Dyskinesia in Experimental Model Parkinson's Disease: Role of Mitochondrial Activities and Monoamines Turnover

Background: Levodopa (or l-DOPA) is the current standard of care for the management of Parkinson's disease (PD), but its chronic administration has been associated with the development of LID (l-DOPA-induced dyskinesia). Fisetin is a dietary flavonoid known for its neuroprotective efficacy. Aim: To determine the neuroprotective potential of fisetin in 6-hydroxydopamine (6-OHDA)-lesioned LID animals. Methods: 6-OHDA (12 µg and L-ascorbic acid [10 µL]) was injected in a substantial nigra of Sprague-Dawley rat to develop PD followed by l-DOPA (20 mg/kg and benserazide HCl [5 mg/kg], 42 days) to induce LID. Rats were concomitantly administered with vehicle or amantadine (40 mg/kg), or fisetin (5, 10, and 25 mg/kg, p.o.) for 42 days with l-DOPA. Results: Chronic l-DOPA administration resulted in progressive abnormal involuntary movements (AIMs viz. axial, forelimb, and orolingual), akinesia (forelimb adjusting steps, FAS), muscular rigidity (catalepsy bar test), muscular coordination, and neurological impairments. Fisetin at doses of 10 and 25 mg/kg effectively reduced (P