Protective effect of ginsenoside Rg1 against MPTP-induced apoptosis in mouse substantia nigra neurons.
OBJECTIVE
To explore the possible mechanism of the ginsenoside Rg1 in protecting substantia nigra neurons from 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced apoptosis in C57BL mice.


METHODS
C57BL male mice were given with MPTP to prepare Parkinson's disease mouse model. Different doses of Rg1 (2.5, 5.0, and 10.0 mg/kg, respectively) were given 3 d prior to MPTP in the pretreatment groups. Nissl staining, TH immunostaining, and TUNEL labeling were used to observe the damage and apoptosis of nigral neurons. The immunohistochemistry assay was used to detect the protein levels of Bcl-2, Bcl-xl, Bax, inducible nitric oxide synthase (iNOS), neuronal NOS (nNOS), and cleaved caspase-3.


RESULTS
Compared with MPTP model group, pretreatment with Rg1 (5.0 and 10.0 mg/kg) was shown to increase the Nissl staining neurons and TH-positive neurons (P<0.01), and to decrease the TUNEL-positive neurons in the substantia nigra zona compacta (P<0.01). Moreover, Rg1 elevated the levels of cleaved caspase-3, Bax, and iNOS, but reduced the levels of Bcl-2 and Bcl-xl (P<0.01).


CONCLUSIONS
Rg1 has protective effect against MPTP-induced apoptosis and this effect may be attributed to enhancing Bcl-2 and Bcl-xl expression, reducing Bax and iNOS expression, and inhibiting activation of caspase-3.
Chen
Xiao-Chun
XC
Fujian Institute of Geriatrics, Union Hospital, Fujian Medical University, Fuzhou 350001, China. ZJCXCH@Public5.FJ.FZ.cn.
Chen
Ying
Y
Zhu
Yuan-Gui
YG
Fang
Fang
F
Chen
Li-Min
LM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D036145:Ginsenosides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D020734:Parkinsonian Disorders / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013378:Substantia Nigra / Q000473:pathology*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D036145:Ginsenosides; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C035054:ginsenoside Rg1