Disruption of neuronal
iron homeostasis and oxidative stress are closely related to the pathogenesis of
Parkinson's disease (PD).
Ginkgetin, a natural
biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the
neuroprotective effects in PD remains unclear. The present study utilized PD models induced by
1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (
MPTP) to explore the neuroprotective ability of
ginkgetin in vivo and in vitro. Our results showed that
ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular
reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile,
ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the
caspase-3 and Bcl2/Bax pathway. Moreover,
ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by
MPTP by dramatically inhibiting the decrease of
tyrosine hydroxylase expression in the substantia nigra and
superoxide dismutase activity in the striatum. Interestingly,
ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile
iron pool through downregulating
L-ferritin and upregulating
transferrin receptor 1. These results indicate that the neuroprotective mechanism of
ginkgetin against neurological injury induced by
MPTP occurs via regulating
iron homeostasis. Therefore,
ginkgetin may provide neuroprotective
therapy for PD and
iron metabolism disorder related diseases.