Coffee Components Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in Vitro: Possible Link between Coffee Consumption and Diabetes Mellitus
Coffee Components Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in Vitro: Possible Link between Coffee Consumption and Diabetes Mellitus
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咖啡成分在体外抑制人胰岛淀粉样多肽的淀粉样蛋白形成：咖啡摄入与糖尿病之间可能存在联系
DOI：
10.1021/jf201702h
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发表时间：
2011-12-28
影响因子：
6.1
通讯作者：
Huan, Kun
中科院分区：
文献类型：
--
作者：
Cheng, Biao;Liu, Xinran;Huan, Kun
全球流行病研究表明，咖啡消费量与代谢性疾病--2型糖尿病(T2 DM)的发病率呈负相关。人胰岛淀粉样多肽(HIAPP)错误折叠被认为是T2 DM的致病因素之一。咖啡提取物有三种主要活性成分：咖啡因、咖啡酸(CA)和绿原酸(CGA)。本研究通过基于硫代黄素-T的荧光发射、透射电子显微镜、圆二色谱、光诱导交联、动态光散射和基于细胞活力的分析，研究了这些主要咖啡成分以及CGA和CA的主要代谢物二氢咖啡酸(DHCA)对hIAPP淀粉样蛋白生成的影响。结果表明，各组分对毒性hIAPP淀粉样蛋白的形成均有不同程度的抑制作用，其中CA延缓hIAPP分子构象转变的作用最强，滞后时间最长，咖啡因的延缓作用最弱。圆二色谱和CDPro去卷积分析表明，当化合物与hIAPP的摩尔比超过5倍时，所有咖啡衍生化合物都影响孵育的hIAPP的二级结构。进一步的基于光诱导交联的齐聚反应和动态光散射研究表明，CA和CGA显著抑制hIAPP齐聚物的形成，而咖啡因对齐聚反应没有显著影响。3种化合物对细胞的保护作用也不同，其中CA的保护效果最好，CGA次之。这些发现表明，饮用咖啡对T2 DM的有益影响可能部分是由于咖啡的主要成分和代谢产物能够抑制hIAPP的毒性聚集。
Global epidemic studies have suggested that coffee consumption is reversely correlated with the incidence of type 2 diabetes mellitus (T2DM), a metabolic disease. The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of T2DM. Coffee extracts have three major active components: caffeine, caffeic acid (CA), and chlorogenic acid (CGA). In this study, the effects of these major coffee components, as well as dihydrocaffeic acid (DHCA) (a major metabolite of CGA and CA), on the amyloidogenicity of hIAPP were investigated by thioflavin-T based fluorescence emission, transmission electronic microscopy, circular dichroism, light-induced cross-linking, dynamic light scattering, and MTT-based cell viability assays. The results suggest that all components show varied inhibitory effects on the formation of toxic hIAPP amyloids, in which CA shows the highest potency in delaying the conformational transition of the hIAPP molecule with the most prolonged lag time, whereas caffeine shows the lowest potency. At a 5-fold excess molar ratio of compound to hIAPP, all coffee-derived compounds affect the secondary structures of incubated hIAPP as suggested by the circular dichroism spectra and CDPro deconvolution analysis. Further photoinduced cross-linking based oligomerization and dynamic light scattering studies suggested CA and CGA significantly suppressed the formation of hIAPP oligomers, whereas caffeine showed no significant effect on oligomerization. Cell protection effects were also observed for all three compounds, with the protection efficiency being greatest for CA and least for CGA. These findings suggest that the beneficial effects of coffee consumption on T2DM may be partly due to the ability of the major coffee components and metabolites to inhibit the toxic aggregation of hIAPP.