title: Neuroprotective effects of Eucommia ulmoides Oliv. and its bioactive constituent work via ameliorating the ubiquitin-proteasome system.
abstract: BACKGROUND
  Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. The purpose of this study was to investigate potential in vivo protective effects of Duzhong against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as well as the bioactive constituents against 1-methyl-4-phenylpyridinium (MPP(+)) toxicity in vitro.
  
  
  METHODS
  Male C57BL/6 mice were intraperitoneally administrated five consecutive injections of MPTP every 24 h at a dose of 30 mg/kg to induce an in vivo PD model. Pole and traction tests were performed in mice to evaluate motor deficits and bradykinesia after the final MPTP administration. The striatal levels of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanilic acid, were measured using a High-performance liquid chromatography-electrical conductivity detector. To further explore the bioactive constituents and protective mechanisms of Duzhong, seven compounds from Duzhong were tested on MPP(+)-treated SH-SY5Y cell lines in vitro. A proteasome enzymatic assay and Cell Counting Kit-8 were performed to examine proteasomal activity and cell viability of Duzhong-treated cells, respectively, after exposure to MPP(+) and proteasome inhibitor MG132.
  
  
  RESULTS
  Duzhong antagonized the loss of striatal neurotransmitters and relieved the associated anomaly in ambulatory locomotor activity in PD mice after a 3-day pre-treatment of Duzhong crude extract. The five Duzhong compounds attenuated MPP(+)-induced dysfunction of protease activity and reduced MG132-induced cytotoxicity.
  
  
  CONCLUSIONS
  Duzhong could serve as a potential candidate for PD treatment, and its mechanism involves the amelioration of the ubiquitin-proteasome system.
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshan Xi Road, Nankai District, Tianjin, 300193, China. cacti1983@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshan Xi Road, Nankai District, Tianjin, 300193, China. sflrq@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshan Xi Road, Nankai District, Tianjin, 300193, China. meijiaojiao851020@163.com.
authors.forename: Meijiao
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshan Xi Road, Nankai District, Tianjin, 300193, China. liuqingqing8913@126.com.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshan Xi Road, Nankai District, Tianjin, 300193, China. yubin_771115@hotmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshan Xi Road, Nankai District, Tianjin, 300193, China. huliminth@126.com.
authors.forename: Limin
authors.initials: L
authors.lastname: Hu
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D015655:1-Methyl-4-phenylpyridinium / Q000009:adverse effects; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D031283:Eucommiaceae / Q000737:chemistry*; D020267:MPTP Poisoning / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000068079:Motor Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D010936:Plant Extracts; D025801:Ubiquitin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D046988:Proteasome Endopeptidase Complex; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine