title: Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts.
abstract: OBJECTIVE
  Saikokeishito (TJ-10) is a Kampo (traditional Japanese herbal) medicine, clinically used for hundreds of years in East Asia. Among its various mechanisms elucidated so far, TJ-10 inhibits the production of transforming growth factor-β1 (TGF-β1) and development of pancreatic fibrosis in vivo. Oxidative damage of normal human dermal fibroblasts (NHDFs) in the corium is a cause of human dermal senescence. Our aim was to determine whether TJ-10 protects NHDFs from premature senescence by hydrogen peroxide (H₂O₂).
  
  
  METHODS
  Premature senescence was induced in NHDFs by 200 μmol/L H₂O₂ for 4 h. Cell viability and the expressions of p53, AMP-activated protein kinase α1 (AMPKα1), AMPKα2, and 14-3-3 protein sigma (14-3-3 σ) were measured in NHDFs treated with TJ-10 for 48 h before exposure to H₂O₂for 4 h.
  
  
  RESULTS
  Cell viability after treatment with 200 μmol/L H₂O₂ for 4 h was similar (about 80%) to after pre-treatment with TJ-10. Ascorbic acid as a control did not protect NHDFs from damage by 200 μmol/L H₂O₂. Treatment with 200 μmol/L H₂O₂tended to up-regulate p53 and to down-regulate SIRT1 and AMPKα1, but had no effect on AMPKα2 and 14-3-3 σ expression. Pretreatment with TJ-10 inhibited H₂O₂-induced up-regulation of p53 and enhanced AMPKα1 expression.
  
  
  CONCLUSIONS
  It is suggested that Saikokeishito has a protective effect on oxidative stress-induced senescence of NHDFs.
authors.affiliation: Medical Research Institute of Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Takata
authors.affiliation: Medical Research Institute of Kanazawa Medical University, Ishikawa, Japan; E-mail: motoo@kanazawa-med.ac.jp.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Motoo
authors.affiliation: Medical Research Institute of Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D020405:Dermis / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020835:Medicine, Kampo / Q000379:methods*; D056564:Sirtuin 1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; C018142:saiko-keishi-to; D006861:Hydrogen Peroxide; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D001205:Ascorbic Acid