Protective effects of St. John's wort extract and its component hyperforin against cytokine-induced cytotoxicity in a pancreatic β-cell line
- 作者：Marta Menegazzi ; Michela Novelli ; Pascale Beffy ; Valentina D’ ; Aleo ; Elisa Tedeschi ; Roberto Lupi ; Elisa Zoratti ; Piero Marchetti ; Hisanori Suzuki ; Pellegrino Masiello
- 关键词：Pancreatic β ; -cells ; Cytokines ; Signal transduction ; Phytochemicals ; Type 1 diabetes
- 刊名：The International Journal of Biochemistry and Cell Biology
- 出版年：2008
- 期刊代码：127_13572725
- 类别：med
- 出版时间：2008
- 卷：40
- 期：8
- 页码：1509-1521
- 文件大小：1074 K
摘要
In both type 1 and type 2 diabetes, increased production of cytokines on autoimmune or metabolic basis is supposed to trigger an inflammatory process leading to dysfunction and death of pancreatic β-cells. Therefore, anti-inflammatory pharmacological approaches aimed at blocking cytokine signalling pathways and consequent cytotoxicity in β-cells are highly advisable. Based on previous evidence of cytokine antagonistic effects in other cell types, we explored the protective action of Hypericum perforatum (St-John's-wort) extract and its component hyperforin against cytokine-induced functional impairment and apoptosis in the INS-1E β-cell line, searching for the underlying mechanisms. The results showed that either St-John's-wort extract or hyperforin (at 1–3 μM) prevented cytokine-induced impairment in glucose-stimulated insulin secretion and protected cells against apoptosis in a dose-dependent fashion. Inducible-NO-synthase expression was also potently hindered by the vegetal compounds. Interestingly, cytokine-induced activations of the signal-transducer-and-activator-of-transcription-1 (STAT-1) and the nuclear-factor-kappaB (NF-κB) were both down-regulated by SJW extract or HPF (range 0.5–5 μM) when evaluated by electrophoretic-mobility-shift-assay. Other transcription factors (CBF-1, SP-1) were unaffected. Components of SJW extract other than HPF were much less effective in down-regulating cytokine signalling. Significantly, inhibition of cytokine-elicited STAT-1 and NF-κB activation was confirmed in isolated rat and human islets incubated in the presence of these vegetal compounds. In conclusion, St-John's-wort extract and hyperforin are non-peptidyl compounds which, at low concentrations, target key mechanisms of cytokine-induced β-cell injury, thereby improving β-cell function and survival. Thus, they are potentially valuable for the prevention or limitation of β-cell loss in diabetes.