Department of Chemistry, Renmin University of China, Beijing 100872, China.
The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Int J Biol Macromol. 2021 Jul 31;183:1067-1078. doi: 10.1016/j.ijbiomac.2021.05.030. Epub 2021 May 7.
Human islet amyloid polypeptide (hIAPP) is widely studied due to its close correlation with the pathogenic mechanism of type II diabetes mellitus (T2DM). Bioflavonoids have been used in the neurodegeneration and diabetes studies. However, the structure-activity relationship remains unclear in many of these compounds. In this work, we performed diverse biophysical and biochemical methods to explore the inhibition of procyanidine on hIAPP and compared with that on amyloid-β (Aβ) protein which is linked to Alzheimer's disease (AD). The procyanidine effectively inhibited the aggregation of hIAPP and Aβ through hydrophobic and hydrogen bonding interactions, it dissolved the aged fibrils into nanoscale particles. The compound also ameliorated the cytotoxicity and the membrane leakage by reducing the peptide oligomerization. The procyanidine showed better binding affinity and inhibitory effects on peptide aggregation and upregulated the cell viability to hIAPP than to Aβ, which could be a prospective inhibitor against hIAPP. This work also offered a possible strategy for T2DM and AD treatments.
人胰岛淀粉样多肽（hIAPP）与 2 型糖尿病（T2DM）的发病机制密切相关，因此受到广泛研究。类黄酮已被用于神经退行性疾病和糖尿病的研究。然而，在许多这些化合物中，其结构-活性关系仍不清楚。在这项工作中，我们采用了多种生物物理和生化方法来研究原花青素对 hIAPP 的抑制作用，并与与阿尔茨海默病（AD）相关的淀粉样β（Aβ）蛋白的抑制作用进行了比较。原花青素通过疏水和氢键相互作用有效抑制了 hIAPP 和 Aβ的聚集，它将老化的纤维溶解成纳米级颗粒。该化合物还通过减少肽寡聚化来减轻细胞毒性和膜渗漏。原花青素对肽聚集的结合亲和力和抑制作用优于 Aβ，对 hIAPP 的上调细胞活力也优于 Aβ，因此可能是 hIAPP 的一种有前景的抑制剂。这项工作还为 T2DM 和 AD 的治疗提供了一种可能的策略。
