Possible mechanisms of the protection of ginsenoside Re against MPTP-induced apoptosis in substantia nigra neurons of Parkinson's disease mouse model.
We have investigated the role of ginsenoside Re (Re) in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of the substantia nigra neurons in the mouse model of Parkinson's disease (PD). C57BL mice have been administrated i.s.c. with MPTP to establish the PD model. Pretreatment groups were given different doses of Re (6.5, 13, 26 mg kg(-1)) i.g. for 13 days. Transmission electron microscope (TEM), tyrosine hydroxythase (TH) immunostaining and TDT-mediated dUTP nick-end labeling (TUNEL) staining have been used to observe the damage of substantia nigral neurons. To measure the expression of inducible nitric oxide synthase (iNOS), Bcl-2, Bax protein and expression of Bcl-2, Bax gene, immunohistochemistry and in situ hybridization have been explored respectively. Western blot analysis has been performed with anti-caspase-3. Pretreatment with Re (13, 26 mg kg(-1)) markedly increases TH-positive neurons and decreases the TUNEL-positive ratio compared with the MPTP model group. Furthermore, Re could enhance the expression of Bcl-2 protein and Bcl-2 mRNA, but reduce the expression of Bax, Bax mRNA, and iNOS, and weaken the cleavage of caspase-3. In summary, ginsenoside Re showed protection from MPTP-induced apoptosis in the PD model mouse nigral neurons and this effect may be attributable to upregulating the expression of Bcl-2 protein, downregulating the expression of Bax, and iNOS protein, and inhibiting the activation of caspase-3.
Xu
Bei-Bei
BB
Physiological Department, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Liu
Chun-Qing
CQ
Gao
Xi
X
Zhang
Wan-Qin
WQ
Wang
Shi-Wei
SW
Cao
Ying-Lin
YL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D036145:Ginsenosides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C049864:ginsenoside Re; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases