title: Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in the MPTP-induced mouse model of Parkinson's disease: Involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways.
abstract: Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress-induced neuron loss is thought to play a crucial role in the pathogenesis of PD. Previous work from our group suggests that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from a traditional Chinese herb, Polygonum multiflorum thunb, can attenuate 1-methyl-4-phenyl pyridium-induced apoptosis in the neuronal cell line PC12, by inhibiting reactive oxygen species generation and modulating c-Jun N-terminal kinases (JNK) activation. Here, we investigated the protective effects of TSG against 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-induced loss of tyrosine hydroxylase positive cells in mice and the underlying mechanisms. The results showed that MPTP-induced loss of tyrosine hydroxylase positive cells and reactive oxygen species generation were prevented by TSG in a dose-dependent manner. The reactive oxygen species scavenger N-acetylcysteine could also mitigate reactive oxygen species generation. Moreover, JNK and P38 were activated by MPTP, but extracellular signal-regulated protein kinases phosphorylation did not change after MPTP treatment. TSG at different doses blocked the activation of JNK and P38. The protective effect of TSG was also associated with downregulation of the bax/bcl-2 ratio, reversed the release of cytochrome c and smac, and inhibited the activation of caspase-3, -6, and -9 induced by MPTP. In conclusion, our studies demonstrated that the protective effects of TSG in the MPTP-induced mouse model of PD are involved, at least in part, in controlling reactive oxygen species-mediated JNK, P38, and mitochondrial pathways.
authors.affiliation: Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.affiliation: Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, PR China.
authors.forename: Songhai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, 518 Hospital of PLA, 11 South Park Road, Xi'an 710043, PR China.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an 710038, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, PR China. Electronic address: tanghaifeng71@163.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Physics and Mathematics, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, PR China. Electronic address: zy04310@fmmu.edu.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, PR China. Electronic address: jzchen57@fmmu.edu.cn.
authors.forename: Jianzong
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D005960:Glucosides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D014446:Tyrosine 3-Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D004298:Dopamine
keywords: MPTP; Mitochondria; Mitogen-activated protein kinase; Parkinson's disease; Reactive oxygen species; Tetrahydroxystilbene-glucoside