4.6 Article

Schizandra arisanensis extract attenuates cytokine-mediated cytotoxicity in insulin-secreting cells

Journal

WORLD JOURNAL OF GASTROENTEROLOGY
Volume 18, Issue 46, Pages 6809-6818

Publisher

BAISHIDENG PUBL GRP CO LTD
DOI: 10.3748/wjg.v18.i46.6809

Keywords

Schizandra arisanensis; C-19 homolignans; Type 1 diabetes; Insulin-secreting cells; Interleukin-1 beta; Interferon-gamma

Funding

  1. National Science Council [NSC94-2314-B-077 -001, NSC101-2320-B-077-003-MY2]
  2. National Research Institute of Chinese Medicine [NRICM95-DHM-04]

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AIM: To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1 beta and interferon-gamma-mediated beta 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 beta cell death. RESULTS: Our results revealed that SA-Et dose-dependently ameliorated cytokine-mediated beta 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 beta cell death. CONCLUSION: This is the first report on SA-Et ameliorating cytokine-mediated beta cell death and dysfunction via anti-apoptotic and insulinotropic actions. (C) 2012 Baishideng. All rights reserved.

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