EGb761 protects against nigrostriatal dopaminergic neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice: role of oxidative stress.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity and behavioral impairment in rodents. Previous studies suggest that oxidative stress, via free radical production, is involved in MPTP-induced neurotoxicity. The MPTP-treated mouse has been the most widely used model for assessing neuroprotective agents for Parkinson's disease. It has been reported previously that EGb761 prevents dopaminergic neurotoxicity of MPTP. This compound is multifunctional via different mechanisms. Here, we report the neuroprotective effect of EGb761 against oxidative stress induced by MPTP in C57BL/6J mice. EGb761 is a patented and well-defined mixture of active compounds extracted from Ginkgo biloba leaves, with neuroprotective effects, exerted probably via its antioxidant or free radical scavenger action. MPTP administration resulted in a significant decrease in striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. Mice receiving EGb761 had significantly attenuated MPTP-induced loss of striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. The neuroprotective effect of EGb761 against MPTP neurotoxicity is associated with blockade of lipid peroxidation and reduction of superoxide radical production (indicated by a down-regulation of Mn-superoxide dismutase activity), both of which are indices of oxidative stress. Behavioral analyses showed that EGb761 improved MPTP-induced impairment of locomotion in a manner that correlated with enhancement of striatal dopamine levels. These findings suggest that, in mice, EGb761 attenuates MPTP-induced neurodegeneration of the nigrostriatal pathway and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.