The abnormal aggregation of human islet amyloid polypeptide (hIAPP) is a crucial pathogenic factor associated with type 2 diabetes (T2D). The development of effective inhibitors to prevent hIAPP aggregation is a common therapeutic strategy against T2D. Lithospermic acid (LA) is a natural compound with diversified biological activities. In this study, electrospray ionization coupled with ion mobility-mass spectrometry, thioflavin T fluorescence assay, Congo red binding assay, Nile red fluorescence assay, circular dichroism spectroscopy, transmission electron microscopy, cell toxicity, lactate dehydrogenase assay (LDH) assay and molecular docking were combined to explore the influence of LA on hIAPP aggregation. Results showed that LA had favorable binding affinity to hIAPP and formed hIAPP-LA complexes, which could alter the relative abundance of the compact and extended conformers and promoted the transition of extended structures to compact conformers. LA also displayed strong inhibitory actions on fibrillation and potential protective effects against hIAPP-induced cell toxicity. Therefore, the obtained results were useful to understand the possible inhibitory mechanism of LA on hIAPP aggregation and provided valuable reference for the screening of potent amyloid inhibitors.

中文翻译：

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通过多种分析方法，精子酸对hIAPP聚集和淀粉样蛋白诱导的细胞毒性的影响。

人胰岛淀粉样多肽（hIAPP）的异常聚集是与2型糖尿病（T2D）相关的重要致病因素。预防hIAPP聚集的有效抑制剂的开发是针对T2D的常见治疗策略。紫精酸（LA）是一种具有多种生物活性的天然化合物。在这项研究中，电喷雾电离结合离子迁移质谱，硫黄素T荧光测定，刚果红结合测定，尼罗红荧光测定，圆二色光谱，透射电子显微镜，细胞毒性，乳酸脱氢酶测定（LDH）和分子对接结合以探讨LA对hIAPP聚集的影响。结果表明，LA对hIAPP具有良好的结合亲和力，并形成了hIAPP-LA复合物，这可能会改变致密构型和扩展构型的相对丰度，并促进了扩展结构向致密构型的过渡。洛杉矶还显示出对原纤维形成强烈的抑制作用以及对hIAPP诱导的细胞毒性的潜在保护作用。因此，获得的结果有助于了解LA对hIAPP聚集的可能抑制机制，并为筛选有效的淀粉样蛋白抑制剂提供有价值的参考。