echinacoside and Parkinson-Disease--Secondary

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.

Topics: Animals; Apoptosis; Axons; bcl-2-Associated X Protein; Blotting, Western; Brain-Derived Neurotrophic Factor; Cell Survival; Chromatography, High Pressure Liquid; Dopamine; Gait Disorders, Neurologic; Glial Cell Line-Derived Neurotrophic Factor; Glycosides; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred C57BL; MPTP Poisoning; Neostriatum; Nerve Growth Factors; Neurons; Parkinson Disease, Secondary; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Tyrosine 3-Monooxygenase

In the present study, we investigated the neuroprotective effects of echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Cistanches salsa, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity. We confirmed that exposure to MPTP in mice leads to permanent behavioral deficits and depletion of dopamine and its metabolites. When administered prior to MPTP, echinacoside reduced behavioral deficits, increased striatal dopamine and dopamine metabolite levels, reduced cell death, and led to a marked increase in tyrosine hydroxylase expression relative to mice treated with MPTP alone. In addition, pre-treatment with echinacoside significantly reduced caspase-3 and caspase-8 activation in 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptosis in cerebellar granule neurons. Taken together, these findings suggest that echinacoside improves the behavioral and neurochemical outcomes in MPTP mice model of Parkinson's disease and inhibits caspase-3 and caspase-8 activation in cerebellar granule neurons, making the compound an attractive candidate treatment for various neurodegenerative disorders, including Parkinson's disease.

Topics: Animals; Apoptosis; Behavior, Animal; Caspase 3; Caspase 8; Cell Death; Cerebellum; Cistanche; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Glycosides; Male; Mice; Mice, Inbred C57BL; MPTP Poisoning; Neurons; Neuroprotective Agents; Parkinson Disease, Secondary; Plant Extracts; Tyrosine 3-Monooxygenase