Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptideand protects pancreatic beta-cells against cytotoxicity
Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptideand protects pancreatic beta-cells against cytotoxicity
复制标题
丹酚酸 B 抑制人胰岛淀粉样多肽的淀粉样蛋白形成并保护胰腺 β 细胞免受细胞毒性
DOI：
10.1002/prot.24216
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发表时间：
2013-04-01
影响因子：
2.9
通讯作者：
Huang, Kun
中科院分区：
文献类型：
--
作者：
Cheng, Biao;Gong, Hao;Huang, Kun
人胰岛淀粉样蛋白多肽（hIAPP）的错误折叠被认为是2型糖尿病（T2DM）的病因之一。丹参是最常用的中药之一，常用于治疗糖尿病的复方中，但其作用机制尚不清楚。因为丹酚酸B （SalB）是丹参水提物中最丰富的生物活性成分。在这项研究中，我们测试了SalB是否对hIAPP的淀粉样变性有任何影响。我们的研究结果清楚地表明，SalB可以显著抑制hIAPP淀粉样蛋白的形成和hIAPP原纤维的分解。此外，基于光交联的寡聚化研究表明，SalB显著抑制hIAPP单体的毒性寡聚化。通过基于mtt的实验也观察到SalB对胰腺INS-1细胞的细胞毒性保护作用，这可能是由于抑制hIAPP诱导的膜破坏效应和减轻线粒体损伤。这些结果为进一步研究SalB对T2DM可能的药理治疗提供了证据。2013的蛋白质。(c) 2012 Wiley期刊有限公司
The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of type 2 diabetes mellitus (T2DM). Salvia miltiorrhiza (Danshen), one of the most commonly used of traditional Chinese medicines, is often used in Compound Recipes for treating diabetes, however with unclear mechanisms. Since salvianolic acid B (SalB) is the most abundant bioactive ingredient of salvia miltiorrhiza water-extract. In this study, we tested whether SalB has any effect on the amyloidogenicity of hIAPP. Our results clearly suggest that SalB can significantly inhibit the formation of hIAPP amyloid and disaggregate hIAPP fibrils. Furthermore, photo-crosslinking based oligomerization studies suggest SalB significantly suppresses the toxic oligomerization of hIAPP monomers. Cytotoxicity protection effects on pancreatic INS-1 cells by SalB were also observed using MTT-based assays, potentially due to the inhibition on the membrane disruption effects and attenuated mitochondria impairment induced by hIAPP. These results provide evidence that SalB may further be studied on the possible pharmacological treatment for T2DM. Proteins 2013. (c) 2012 Wiley Periodicals, Inc.