Tripchlorolide protects against MPTP-induced neurotoxicity in C57BL/6 mice.
Many current studies of Parkinson's disease (PD) suggest that inflammation is involved in the neurodegenerative process. Tripchlorolide (TW397), a traditional Chinese herbal compound with anti-inflammatory and immunosuppressive properties, has been shown to protect dopaminergic neurons against, and restore their function after, the neurotoxicity induced by 1-methyl-4-phenylpyridinium ions in vitro. This study was designed to investigate the effect of TW397 in vivo in the PD model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned C57BL/6 mice. In the animals that received vehicle-only (i.e., no TW397) treatment with MPTP i.p. injection, the survival ratios of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra pars compacta and TH-IR fibres in the striatum were only 59 and 13%, respectively, compared with the normal controls. Intriguingly, in conjunction with MPTP, treatment with TW397, 1 microg/kg for 16 days, once per day, dramatically improved the survival rate of the TH-IR neurons and TH-IR fibres to 80 and 43% of the control. The treatment with TW397 also significantly improved the level of dopamine in the substantia nigra and striatum to 157 and 191%, respectively, of the MPTP- plus vehicle-treated group. In addition, in MPTP-treated animals the rota-rod performances of those treated with 0.5 or 1 microg/kg TW397 were significantly improved, by approximately 2- and 3-fold, respectively, relative to vehicle-treated animals. The neuroprotective effect of TW397 was coincident with an attenuated astroglial response within the striatum. These data demonstrate a neuroprotective action of TW397 in vivo against MPTP toxicity, with important implications for the treatment of PD.
Hong
Zhen
Z
Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025 China.
Wang
Gang
G
Gu
Jing
J
Pan
Jing
J
Bai
Li
L
Zhang
Shi
S
Chen
Sheng-Di
SD
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D008124:Locomotion / Q000187:drug effects; D020267:MPTP Poisoning / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D009412:Nerve Fibers / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents; D010616:Phenanthrenes / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004224:Diterpenes; D018696:Neuroprotective Agents; D010616:Phenanthrenes; C068051:tripchlorolide; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine