KMID : 0363620080290040094
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Journal of Korean Oriental Medicine 2008 Volume.29 No. 4 p.94 ~ p.103
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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
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Lee Kap-Duk
Park Yong-Ki Kim Kwang-Jin
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Abstract
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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.
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KEYWORD
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Celastrus orbiculatus, celastrol, dopaminergic neuron, neuroprotection, Parkinson¡¯s disease
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