title: Neuroprotective effect of modified Chungsimyeolda-tang, a traditional Korean herbal formula, via autophagy induction in models of Parkinson's disease.
abstract: OBJECTIVE
  Previous studies in our laboratory revealed the neuroprotective effect of modified Yeoldahanso-tang (MYH) in models of Parkinson׳s disease (PD). In this study, we investigated another traditional Korean herbal formula, modified Chungsimyeolda-tang (termed DG), as a potential treatment for PD. Chungsimyeolda-tang has been used in Korea to treat cerebrovascular diseases, such as stroke. Here, we verify the neuroprotective and autophagy-inducing effects of DG to evaluate any potential anti-parkinsonian properties.
  
  
  METHODS
  1-Methyl-4-phenylpyridinium (MPP(+)) and rotenone were used to induce cytotoxicity in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Cell viability was measured using an MTT assay. Induction of autophagy by DG in NGF-differentiated PC12 cells was measured using an immunoblotting assay with an LC3 antibody. The proteasomal inhibitor lactacystin was used to induce ubiquitin-proteasome system (UPS) dysfunction in NGF-differentiated PC12 cells. DG-mediated clearance of aggregated proteins was measured using an immunoblotting assay with a ubiquitin antibody.
  
  
  CONCLUSIONS
  Our findings indicate that DG robustly protects NGF-differentiated PC12 cells against the neurotoxic effects of MPP(+) and rotenone in an in vitro model. Furthermore, DG protects NGF-differentiated PC12 cells against lactacystin-induced cell death. This effect is partially mediated by an increased autophagy associated with the enhanced degradation of aggregated proteins. This study suggests that DG is an attractive candidate drug for inducing autophagy and, therefore, may represent a promising strategy to prevent diseases associated with misfolded/aggregated proteins in various neurodegenerative disorders, including Parkinson׳s disease.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Gangwon-do, 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: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University, School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: Sungkwon
authors.initials: S
authors.lastname: Chung
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Gangwon-do, Republic of Korea.
authors.forename: Hee Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Gangwon-do, Republic of Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Cha
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University, School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: Hyungun
authors.initials: H
authors.lastname: Oh
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Gangwon-do, Republic of Korea.
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Gu
authors.affiliation: Department of Life and Nanopharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
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, Gangwon-do, Republic of Korea. Electronic address: hoyang@kist.re.kr.
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D055670:Medicine, Korean Traditional; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D012402:Rotenone
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D010936:Plant Extracts; C000600921:chungsimyeolda-tang; D012402:Rotenone; D015655:1-Methyl-4-phenylpyridinium
keywords: Autophagy; DG; Lactacystin; Neuroprotection; PC12 cells; Parkinson׳s disease