Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Biochem Biophys Res Commun. 2012 Mar 16;419(3):495-9. doi: 10.1016/j.bbrc.2012.02.042. Epub 2012 Feb 14.
In type 2 diabetes mellitus (T2DM), misfolded human islet amyloid polypeptide (hIAPP) forms amyloid deposits in pancreatic islets. These amyloid deposits contribute to the dysfunction of β-cells and the loss of β-cell mass in T2DM patients. Inhibition of hIAPP fibrillization has been regarded as a potential therapeutic approach for T2DM. Silibinin, a major active flavonoid extracted from herb milk thistle (Silybum marianum), has been used for centuries to treat diabetes in Asia and Europe with unclear mechanisms. In this study, we tested whether silibinin has any effect on the amyloidogenicity of hIAPP. Our results provide first evidence that silibinin inhibits hIAPP fibrillization via suppressing the toxic oligomerization of hIAPP and enhances the viability of pancreatic β-cells, therefore silibinin may serve as a potential therapeutic agent for T2DM.
在 2 型糖尿病（T2DM）中，错误折叠的人胰岛淀粉样多肽（hIAPP）在胰岛中形成淀粉样沉积物。这些淀粉样沉积物导致β细胞功能障碍和 T2DM 患者β细胞数量减少。抑制 hIAPP 纤维化已被认为是治疗 T2DM 的一种潜在方法。水飞蓟素是从草药奶蓟（Silybum marianum）中提取的主要活性类黄酮，几个世纪以来，它一直被亚洲和欧洲用于治疗糖尿病，但作用机制尚不清楚。在这项研究中，我们测试了水飞蓟素是否对 hIAPP 的淀粉样变性有任何影响。我们的研究结果首次提供了证据，表明水飞蓟素通过抑制 hIAPP 的毒性寡聚化来抑制 hIAPP 的纤维化，并增强胰腺β细胞的活力，因此水飞蓟素可能作为治疗 T2DM 的潜在药物。
