Abstract
Neurodegeneration is one of the primary etiologies in the onset of Parkinson's disease.
In the quest for a new antiparkinsonism treatment the potential benefits of puerarin
from the roots of Pueraria lobata have been recognized. Thus, we examined whether puerarin is capable to protect dopaminergic
neurons of the substantia nigra against 6-hydroxydopamine induced neuronal cell death.
Our data showed that the intraperitoneal administration of 0.12 mg/kg/day puerarin
over 10 days reduced the 6-hydroxydopamine-induced decrease of tyrosine hydroxylase-positive
cell counts. Analysis of apoptosis via DNA fragmentation by the terminal deoxynucleotidyl
transferase dUTP nick-end labeling assay proved that puerarin could prevent 6-hydroxydopamine-induced
apoptosis. As an additional apoptotic cell death marker, the BAX and BCL-2 expression
levels were investigated using immunohistochemistry. Whereas 6-hydroxydopamine increased
the level of Bax (p < 0.05), the coadministrated puerarin significantly antagonized
this effect in a dose-dependent manner. Bcl-2 expression was not affected. Analysis
of the dopamine, dihydroxyphenylacetic acid, and L-dihydroxy-phenyl-alanine contents
of 6-hydroxydopamine-treated animals by HPLC revealed that puerarin was capable to
restore the contents of dopamine and its metabolites. Moreover, the expression level
of glial cell line-derived neurotrophic factor in the striatum was higher in puerarin
than in rats treated with 6-hydroxydopamine alone. These results suggest that puerarin
develops its neuroprotective effect against 6-hydroxydopamine-induced neurotoxicity
in the substantia nigra through the inhibition of apoptotic signaling pathways and
upregulation of glial cell line-derived neurotrophic factor expression in the striatum.
Key words
puerarin -
Pueraria lobata
- Fabaceae - Parkinson's disease - apoptosis - GDNF
References
in vivo .
Nature.
1995;
373
335-339
1 Equal contribution to this article.
qinglin_lee@hotmail.com
