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KMID : 0363620080290040094
Journal of Korean Oriental Medicine
2008 Volume.29 No. 4 p.94 ~ p.103
Protective Effects of Celastrol, the Triterpenoid Component of Celastrus Orbiculatus, on Dopaminergic Neuronal Cells in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned Parkinson¡¯s Disease Rats
Lee Kap-Duk

Park Yong-Ki
Kim Kwang-Jin
Abstract
Objectives: The aim of this study was to determine whether celastrol, the triterpenoid component of Celastrus orbiculatus, offers neuroprotection against Parkinson¡¯s disease (PD) in mice administered 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine(MPTP).

Methods: We examined how celastrol affected MPTP-induced neuronal loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in substantia nigra pars compacta (SNpc) in the midbrain of mice. C57BL/6J mice were divided into four groups: (1) saline-saline, (2) saline-celastrol, (3) MPTP-saline, and (4) MPTP-celastrol. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (18mg/kg) at 2 h intervals and then i.p. administered celastrol (3mg/kg) two times at 12 h after last celastrol administration. Expression of TH on the SNpc of brain tissues were analyzed at 7 days after the treatments by immunohistochemistry and Western blot.

Results: Immunohistochemical analysis using TH antibody showed that celastrol provided significantly protective effects against MPTP-induced loss of TH-positive dopaminergic neurons in the SNpc region of the midbrain of mice. Our Western blot study also showed that celastrol significantly inhibits the MPTP-induced neuronal damage via the up-regulation of TH protein levels in MPTP mice.

Conclusions: The present results suggest that it may be possible to use celastrol for the prevention of nigral degenerative disorders including PD, caused by exposure to toxic substances.
KEYWORD
Celastrus orbiculatus, celastrol, dopaminergic neuron, neuroprotection, Parkinson¡¯s disease
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