Neurotrophic and neurorescue effects of Echinacoside in the subacute MPTP mouse model of Parkinson's disease.
Many experiments support the notion that augmentation of neurotrophic factors' (NTFs) activity, especially glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) could prevent or halt the progress of neurodegeneration in Parkinson's disease (PD). However, application of NTFs as therapeutic agents for PD is hampered by the difficulty in delivering them to specific brain regions safely and effectively. Another potential strategy is to stimulate the endogenous expression of NTFs. In this study, we investigated the effects of Echinacoside (ECH), a monomer extracted from herbs, on rescuing dopaminergic function in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned mice. We found that oral administration of ECH (30 mg/kg/day for 14 days) to MPTP-treated mice, commencing after impairment of the nigrstriatal system, suppressed the reduction of nigral dopaminergic neurons, striatal fibers, dopamine and dopamine transporter to 134.24%, 203.17%, 147.25% and 154.72 of MPTP-lesioned animals respectively (p<0.05). There was a relative elevation in expression of GDNF and BDNF mRNA (2.94 and 3.75-fold) and protein (184.34% and 185.93%) in ECH treated mice compared with vehicle-treated MPTP-lesioned mice (p<0.05). In addition, the apoptosis cells and Bax/Bcl-2 ratio of mRNA and protein in MPTP-lesioned mice significantly increased, and these effects could be prevented by ECH. At the 7th and 14th days of ECH treatment, the gait disorder displayed obvious improvement (p<0.05). These findings demonstrate that ECH is probably a novel, orally active, non-peptide inducer of NTFs and inhibitor of apoptosis, and they provide preclinical support for therapeutic potential of this compound in the treatment of PD.
Zhao
Qing
Q
Laboratory of Neurology, Institute of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Gao
Junpeng
J
Li
Wenwei
W
Cai
Dingfang
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000201:enzymology; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D020233:Gait Disorders, Neurologic / Q000139:chemically induced / Q000523:psychology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis; D006027:Glycosides / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000201:enzymology; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006027:Glycosides; D009414:Nerve Growth Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D014446:Tyrosine 3-Monooxygenase; C060297:echinacoside; D004298:Dopamine