title: Anti-apoptotic effect of modified Chunsimyeolda-tang, a traditional Korean herbal formula, on MPTP-induced neuronal cell death in a Parkinson's disease mouse model.
abstract: BACKGROUND
  The modified-Chungsimyeolda-tang (DG) is an important traditional Korean herbal formula used in traditional oriental medicine for treatment of cerebrovascular disorders, including stroke. The formula is based on the book "Dongui Sasang Shinpyun".
  
  
  OBJECTIVE
  In the previous studies, the neuroprotective effect of DG is demonstrated in an in vitro Parkinson's disease (PD) model, and in this study, the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD is used to evaluate the behavioral effect of DG and possible mechanism through anti-apoptosis of DG. 6-Hydroxydopamine (6-OHDA) also is used to evaluate the anti-apoptosis effect of DG in SH-SY5Y cells.
  
  
  METHODS
  MPTP was used to evaluate the behavioral damage and neurotoxicity in mice. The bradykinesia symptom was measured by a Pole test and a Rota-rod test in mice. Also the loss of tyrosine hydroxylase (TH)-positive neurons induced by MPTP was examined by an immunohistochemical assay. The DG-mediated anti-apoptosis effect was measured using an immunoblotting assay with apoptosis-related markers such as Bax and cleaved caspase-3. DG and 1-methyl-4-phenylpyridinium (MPP(+)) were co-treated with primary dopaminergic neurons to evaluate the protective effect of DG. The expression of caspase-3 and PARP was measured to detect the protective effect of DG from the damage by 6-OHDA.
  
  
  CONCLUSIONS
  The treatment with DG resulted in prophylactic effects on MPTP-induced Parkinsonian bradykinesia and the immunohistochemical analysis showed that DG provided the neuroprotection against the MPP(+)-induced dopaminergic neurons loss through the anti-apoptosis effect. The present results suggested that it might be possible to use DG for the prevention of substantia nigra pars compacta (SNpc) degeneration induced by exposure to the toxic substances, such as MPTP/MPP(+), in PD mouse model.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea; Department of Biological Chemistry, University of Science & Technology (UST), Daejeon 305-350, Republic of Korea; College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Life and Nanopharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Gunhyuk
authors.initials: G
authors.lastname: Park
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea; Department of Sasang Constitution Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Bae
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
authors.forename: Joonki
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: msohok@khu.ac.kr.
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea; Department of Biological Chemistry, University of Science & Technology (UST), Daejeon 305-350, Republic of Korea. Electronic address: hoyang@kist.re.kr.
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects; D006801:Humans; D007723:Korea; D008297:Male; D008519:Medicine, Traditional; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009498:Neurotoxins; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; C494827:Bax protein, mouse; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; C000600921:chungsimyeolda-tang; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D053148:Caspase 3
keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 6-Hydroxydopamine; Apoptosis; Modified-Chungsimyeolda-tang; Neuroprotection; Parkinson's disease