Baicalein enhances the effect of low dose Levodopa on the gait deficits and protects dopaminergic neurons in experimental Parkinsonism

摘要

Parkinson's Disease (PD) is the second most common neurodegenerative disease with the clinical characteristics of gait deficits. The classical symptomatic treatment for PD is Levodopa (L-DOPA) which brings a plethora of side effects and dosage problems in a prolonged drug regimen. Baicalein is a flavonoid extracted from Scutellaria baicalensis Georgi with the properties of neuroprotection. In this study, we investigated the ameliorative effect of baicalein with low dose L-DOPA (25 mg/kg) on the 1-methyl-4-phe nyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinsonism. The gait variability was assessed by a computer-assisted gait analysis system Catwalk. The results showed that MPTP challenged mice had significant gait deficits on dynamic paw function and posture stability. L-DOPA reversed the MPTP induced gait deficits and the effect was positively dose-dependent. The combined treatment of baicalein and under threshold dose of L-DOPA significantly improved gait functions, compared with exclusive low dose L-DOPA treatment, and the effect was comparable with high dose L-DOPA treatment. The histological assessment demonstrated that the Tyrosine hydroxylase expression increased in all the baicalein stratified groups, which suggest baicalein might have the neuroprotective effect to retain the dopaminergic neurons or enhance the dopaminergic neuron regeneration after MPTP injection. This neuroprotection probably depended on altering the inflammatory response and resisting the apoptosis through the underlying mechanism investigation. Our study provides experimental evidence that the combination of L-DOPA and baicalein might be a potential treatment for Parkinson's disease. The synergistic interaction of baicalein and L-dopa treatment might reduce the side-effect of the normal to high dose L-DOPA used today. (C) 2019 Published by Elsevier Ltd.