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首页> 外文期刊>The Journal of Nutritional Biochemistry >Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin
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Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin

机译：橄榄苦苷苷元可阻止人胰岛淀粉样多肽的细胞毒性淀粉样蛋白聚集

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Pancreatic amyloid deposits of amylin are a hallmark of Type II diabetes and considerable evidence indicates that amylin oligomers are cytotoxic to beta-cells. Many efforts are presently spent to find out naturally occurring molecules, or to design synthetic ones, able to hinder amylin aggregation or to protect cells against aggregate cytotoxicity. In this context, a protective effect of some polyphenols against amyloid cytotoxicity was reported. Actually dietary polyphenols are endowed with multiple health benefits, and extra virgin olive oil is attracting increasing interest as a source of these substances. Here, we investigated the effects on amylin aggregation and cytotoxicity of the secoiridoid oleuropein aglycon, the main phenolic component of extra virgin olive oil. We found that oleuropein, when present during the aggregation of amylin, consistently prevented its cytotoxicity to RIN-5F pancreatic beta-cells, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide test and caspase-3 activity assay. A lack of interaction with the cell membrane of amylin aggregates grown in the presence of oleuropein was shown by fluorescence microscopy and synthetic lipid vesicle permeabilization. Moreover, our ThT assay, circular dichroism analysis and electron microscopy images suggested that oleuropein interferes with amylin aggregation, resulting in a different path skipping the formation of toxic pre-fibrillar aggregates. These results provide a molecular basis for some of the benefits potentially coming from extra virgin olive oil consumption and pave the way to further studies on the possible pharmacological use of oleuropein to prevent or to slow down the progression of type II diabetes
机译：胰岛淀粉样淀粉样蛋白的胰淀粉样蛋白沉积物是II型糖尿病的标志，大量证据表明胰岛淀粉样蛋白低聚物对β细胞具有细胞毒性。当前花费了许多努力来发现天然分子，或设计能够阻碍胰岛淀粉样多肽聚合或保护细胞免受聚合细胞毒性的合成分子。在这种情况下，据报道某些多酚对淀粉样细胞毒性具有保护作用。实际上，膳食中的多酚具有多种健康益处，而特级初榨橄榄油作为这些物质的来源正受到越来越多的关注。在这里，我们调查了特级初榨橄榄油的主要酚类成分-类茄形油橄榄苦苷糖苷配基对胰岛淀粉样多肽聚合和细胞毒性的影响。我们发现，橄榄苦苷当在胰岛淀粉样多肽的聚集过程中存在时，如3- [4,5-二甲基噻唑-2-基] -2,5-二苯基四唑鎓所测定的那样，始终抑制其对RIN-5F胰腺β细胞的细胞毒性。溴化物测试和caspase-3活性测定。通过荧光显微镜和合成脂质囊泡通透性显示，在橄榄苦苷存在下生长的胰岛淀粉样多肽聚集体与细胞膜缺乏相互作用。此外，我们的ThT分析，圆二色性分析和电子显微镜图像表明，橄榄苦苷干扰胰岛淀粉样多肽的聚集，从而导致了一条不同的途径，从而跳过了有毒的原纤维前聚集物的形成。这些结果为额外食用初榨橄榄油可能带来的某些益处提供了分子基础，并为进一步研究橄榄苦苷可能预防或减缓II型糖尿病的进展铺平了道路

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