title: Schizandra arisanensis extract attenuates cytokine-mediated cytotoxicity in insulin-secreting cells.
abstract: OBJECTIVE
  To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1β and interferon-γ-mediated β cell death and abolition of insulin secretion.
  
  
  METHODS
  By employing BRIN-BD11 cells, the effects of SA-Et administration on cytokine-mediated cell death and abolition of insulin secretion were evaluated by a viability assay, cell cycle analysis, and insulin assay. The associated gene and protein expressions were also measured. In addition, the bioactivities of several peak compounds collected from the SA-Et were tested against cytokine-mediated β cell death.
  
  
  RESULTS
  Our results revealed that SA-Et dose-dependently ameliorated cytokine-mediated β cell death and apoptosis. Instead of suppressing inducible nitric oxide synthase/nitric oxide cascade or p38MAPK activity, suppression of stress-activated protein kinase/c-Jun NH2-terminal kinase activity appeared to be the target for SA-Et against the cytokine mix. In addition, SA-Et provided some insulinotropic effects which re-activated the abolished insulin exocytosis in cytokine-treated BRIN-BD11 cells. Finally, schiarisanrin A and B isolated from the SA-Et showed a dose-dependent protective effect against cytokine-mediated β cell death.
  
  
  CONCLUSIONS
  This is the first report on SA-Et ameliorating cytokine-mediated β cell death and dysfunction via anti-apoptotic and insulinotropic actions.
authors.affiliation: Division of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, Taipei 112, Taiwan, China.
authors.forename: Yi-Shin
authors.initials: YS
authors.lastname: Hsu
authors.forename: Yao-Haur
authors.initials: YH
authors.lastname: Kuo
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Cheng
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.forename: Hui-Kang
authors.initials: HK
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D032141:Schisandra / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D053583:Interleukin-1beta; D010936:Plant Extracts; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose