title: The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in models of Parkinson's disease.
abstract: OBJECTIVE
  Modified Yeoldahanso-tang (MYH) is a Korean herbal formula, containing 10 herbs: Pueraria lobata (Willd.) Ohwi, Angelica tenuissima Nakai, Scutellaria baicalensis Georgi, Platycodon grandiflorum (Jacq), Angelicae Dahurica, Cimicifuga heracleifolia Kom, Raphanus sativa L., Polygala tenuifolia (Willd.), Acorus gramineus Soland. and Dimocarpus longan Lour. The constitutive ratio of the ten herbs is at 6:4:2:1:2:2:2:4:6:6 in dry weight. MYH has been used to treat amnesia, hypochondria and dementia in Korea. In this study, we explored the possibility of using MYH in the prevention and treatment of Parkinson's disease (PD). Specifically, we made an effort to demonstrate the neuroprotective effects of MYH using experimental methods similar to those used in a recent study of PD.
  
  
  METHODS
  1-Methyl-4-phenylpyridinium (MPP+) (400μM) was used to induce cytotoxicity in NGF (nerve growth factor)-differentiated PC12 cells. Cell viability was measured using a MTT assay. Induction of autophagy by MYH in NGF-differentiated PC12 cells was measured using an immunoblotting assay with LC3 and beclin 1 antibodies. The proteasomal inhibitor lactacystin (10μM) was used to cause UPS dysfunction in NGF-differentiated PC12 cells. Clearance of aggregated proteins by MYH was measured using an immunoblotting assay with an ubiquitin antibody. 1-Methyl-4-phenyl-1,2,3,6-tetrahydrophenylpyridine (MPTP) (20mg/kg, 4 times i.p.) caused substantia nigra injuries in C57BL/6 mice. Dopamine (DA) neurons were identified using a tyrosine hydroxylase-immunohistochemistry (TH-IHC) assay with a rabbit anti-TH antibody.
  
  
  RESULTS
  Our findings indicate that MYH provides protection against MPP+-induced injury in NGF-differentiated PC12 cell. And MYH provides neuroprotection against lactacystin-induced NGF-differentiated PC12 cell death, which effect is partially mediated by autophagy enhancement through enhanced degradation of aggregated proteins. Additionally, in a C57BL/6 mice model with MPTP-induced substantia nigra injuries, MYH inhibits both the loss of TH-positive neurons in the substantia nigra pars compacta (SNpc) and the reduction of the optical density of TH-IR fibers in the striatum (ST).
  
  
  CONCLUSIONS
  All of our results indicate that MYH treatment has neuroprotective effects that are partially mediated by autophagy enhancement. MYH may be a promising herbal formula for the prevention and treatment of neurodegenerative diseases, especially PD.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, 290 Daejeon-dong, Gangneung, Gangwon-do 210-340, South Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Bae
authors.forename: Taekwon
authors.initials: T
authors.lastname: Ahn
authors.forename: Sungkwon
authors.initials: S
authors.lastname: Chung
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
authors.forename: Hyeonseok
authors.initials: H
authors.lastname: Ko
authors.forename: Hyungun
authors.initials: H
authors.lastname: Oh
authors.forename: Gunhyuk
authors.initials: G
authors.lastname: Park
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D008297:Male; D055670:Medicine, Korean Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D010936:Plant Extracts; D011506:Proteins; D025801:Ubiquitin; C067713:lactacystin; D020932:Nerve Growth Factor; D046988:Proteasome Endopeptidase Complex; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D000111:Acetylcysteine