Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 14, 2012; 18(46): 6809-6818
Published online Dec 14, 2012. doi: 10.3748/wjg.v18.i46.6809
Schizandra arisanensis extract attenuates cytokine-mediated cytotoxicity in insulin-secreting cells
Yi-Shin Hsu, Yao-Haur Kuo, Hui-Ling Cheng, Peter R Flatt, Hui-Kang Liu
Yi-Shin Hsu, Yao-Haur Kuo, Hui-Kang Liu, Division of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, Taipei 112, Taiwan, China
Yao-Haur Kuo, Hui-Ling Cheng, Graduate Institute of Integrated Medicine, China Medical University, Taichung 404, Taiwan, China
Peter R Flatt, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland BT52 1SA, United Kingdom
Author contributions: Hsu YS and Liu HK were responsible for all bio-assays, research design, data analysis and manuscript writing; Kuo YH and Cheng HL were responsible for crude extract preparation, compound preparation and chemical analysis, and part of the manuscript writing; Flatt PR contributed to manuscript drafting and discussions on the results.
Supported by National Science Council, No. NSC94-2314-B-077-001, No. NSC101-2320-B-077-003-MY2; and National Research Institute of Chinese Medicine, No. NRICM95-DHM-04
Correspondence to: Dr. Hui-Kang Liu, Division of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, 155-1 Li-Nong Street, Section 2, Taipei 112, Taiwan, China. hk.liu@nricm.edu.tw
Telephone: +886-2-28201999 Fax: +886-2-28250743
Received: July 10, 2012
Revised: September 18, 2012
Accepted: September 22, 2012
Published online: December 14, 2012
Abstract

AIM: 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.

CONCLUSION: This is the first report on SA-Et ameliorating cytokine-mediated β cell death and dysfunction via anti-apoptotic and insulinotropic actions.

Keywords: Schizandra arisanensis; C19 homolignans; Type 1 diabetes; Insulin-secreting cells; Interleukin-1β; Interferon-γ