Puerarin protects dopaminergic neurons against 6-hydroxydopamine neurotoxicity via inhibiting apoptosis and upregulating glial cell line-derived neurotrophic factor in a rat model of Parkinson's disease.
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.
Zhu
Guoqi
G
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, PR China.
Wang
Xuncui
X
Chen
Yuefa
Y
Yang
Shu
S
Cheng
Hui
H
Wang
Ning
N
Li
Qinglin
Q
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006892:Hydroxydopamines / Q000633:toxicity; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018517:Plant Roots; D029908:Pueraria / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013194:Staining and Labeling; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D006892:Hydroxydopamines; D007529:Isoflavones; D018696:Neuroprotective Agents; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; C033607:puerarin