title: Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions.
abstract: Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions.
  
  
  BACKGROUND
  Dangguijakyak-san (DJS), a famous traditional herbal formula, has long been used to treat gynecological disorders, including postmenopausal symptoms. This study evaluated the effects and mechanism of DJS on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a postmenopausal mouse model induced by ovariectomy.
  
  
  METHODS
  Three weeks after ovariectomy, C57bl/6 female mice were divided randomly into (1) control, (2) MPTP (30 mg/kg/day, i.p., 5 days), (3) MPTP+estrogen (50 μg/kg/day, i.p., 5 days), and (4) MPTP+DJS (50 mg/kg/day, p.o., 5 days) groups. We investigated the behavioral recovery and dopamine neuron protection of DJS using the pole test and tyrosine hydroxylase (TH) immunohistochemistry. We also explored the mechanism by assessing the protein expression of Bax, Bcl-2, cytochrome c, and cleaved caspase-3.
  
  
  RESULTS
  DJS treatment restored the movement behavior impaired by MPTP, showing a similar or better effect than estrogen. DJS protected TH-immunoreactive cells and fibers in the nigrostriatal region from MPTP toxicity. In addition, DJS inhibited the Bcl-2 decrease and Bax increase in mitochondria, cytochrome c release to the cytosol, and caspase-3 activation induced by MPTP.
  
  
  CONCLUSIONS
  DJS showed behavior recovery and dopamine neuron protection against MPTP-induced toxicity via anti-apoptotic activities in ovariectomized female mice. These results suggest that DJS treatment is effective for postmenopausal neurodegenerative diseases.
authors.affiliation: Department of Oriental Gynecology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Deok-Sang
authors.initials: DS
authors.lastname: Hwang
authors.forename: Hyo Geun
authors.initials: HG
authors.lastname: Kim
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009068:Movement / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010052:Ovariectomy; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D055441:Poria; D017698:Postmenopause; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D004967:Estrogens; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D053148:Caspase 3