Matsuda Takeru, Ferreri Kevin, Todorov Ivan, Kuroda Yoshikazu, Smith Craig V, Kandeel Fouad, Mullen Yoko
Southern California Islet Cell Resources Center, Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center/Beckman Research Institute, Duarte, California 91010, USA.
Endocrinology. 2005 Jan;146(1):175-85. doi: 10.1210/en.2004-0850. Epub 2004 Sep 30.
Silymarin is a polyphenolic flavonoid that has a strong antioxidant activity and exhibits anticarcinogenic, antiinflammatory, and cytoprotective effects. Although its hepatoprotective effect has been well documented, the effect of silymarin on pancreatic beta-cells is largely unknown. In this study, the effect of silymarin on IL-1beta and/or interferon (IFN)-gamma-induced beta-cell damage was investigated using RINm5F cells and human islets. IL-1beta and/or IFN-gamma induced cell death in a time-dependent manner in RINm5F cells. The time-dependent increase in cytokine-induced cell death appeared to correlate with the time-dependent nitric oxide (NO) production. Silymarin dose-dependently inhibited both cytokine-induced NO production and cell death in RINm5F cells. Treatment of human islets with a combination of IL-1beta and IFN-gamma (IL-1beta+IFN-gamma), for 48 h and 5 d, resulted in an increase of NO production and the impairment of glucose-stimulated insulin secretion, respectively. Silymarin prevented IL-1beta+IFN-gamma-induced NO production and beta-cell dysfunction in human islets. These cytoprotective effects of silymarin appeared to be mediated through the suppression of c-Jun NH2-terminal kinase and Janus kinase/signal transducer and activator of transcription pathways. Our data show a direct cytoprotective effect of silymarin in pancreatic beta-cells and suggest that silymarin may be therapeutically beneficial for type 1 diabetes.
水飞蓟素是一种具有强大抗氧化活性的多酚类黄酮，具有抗癌、抗炎和细胞保护作用。尽管其肝脏保护作用已得到充分证明，但水飞蓟素对胰腺β细胞的作用在很大程度上尚不清楚。在本研究中，使用RINm5F细胞和人胰岛研究了水飞蓟素对白细胞介素-1β（IL-1β）和/或干扰素（IFN）-γ诱导的β细胞损伤的影响。IL-1β和/或IFN-γ在RINm5F细胞中以时间依赖性方式诱导细胞死亡。细胞因子诱导的细胞死亡的时间依赖性增加似乎与一氧化氮（NO）产生的时间依赖性相关。水飞蓟素剂量依赖性地抑制RINm5F细胞中细胞因子诱导的NO产生和细胞死亡。用IL-1β和IFN-γ（IL-1β + IFN-γ）联合处理人胰岛48小时和5天，分别导致NO产生增加和葡萄糖刺激的胰岛素分泌受损。水飞蓟素可预防人胰岛中IL-1β + IFN-γ诱导的NO产生和β细胞功能障碍。水飞蓟素的这些细胞保护作用似乎是通过抑制c-Jun氨基末端激酶和Janus激酶/信号转导和转录激活因子途径介导的。我们的数据显示了水飞蓟素对胰腺β细胞的直接细胞保护作用，并表明水飞蓟素可能对1型糖尿病具有治疗益处。
