Tanaka Taisei, Betkekar Vipul V, Ohmori Ken, Suzuki Keisuke, Shigemori Hideyuki
Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, Japan.
Pharmaceuticals (Basel). 2021 Oct 31;14(11):1118. doi: 10.3390/ph14111118.
The number of people worldwide suffering from Alzheimer's disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates in the pancreas are considered cytotoxic and the cause of the development of AD and T2D, respectively. Thus, inhibiting amyloid polypeptide aggregation and disaggregation existing amyloid aggregates are promising approaches in the therapy and prevention against both diseases. Therefore, in this research, we evaluated the Aβ/hIAPP anti-aggregation and disaggregation activities of A-type procyanidins - and their substructures and , by conducting structure-activity relationship studies and identified the active site. The thioflavin-T (Th-T) assay, which quantifies the degree of aggregation of amyloid polypeptides based on fluorescence intensity, and transmission electron microscopy (TEM), employed to directly observe amyloid polypeptides, were used to evaluate the activity. The results showed that catechol-containing compounds - exhibited Aβ/hIAPP anti-aggregation and disaggregation activities, while compound , without catechol, showed no activity. This suggests that the presence of catechol is important for both activities. Daily intake of foods containing A-type procyanidins may be effective in the prevention and treatment of both diseases.
全球患有阿尔茨海默病（AD）和2型糖尿病（T2D）的人数正在上升。淀粉样多肽被认为与这两种疾病的发病有关。在大脑中聚集的淀粉样β蛋白（Aβ）和在胰腺中聚集的人胰岛淀粉样多肽（hIAPP）分别被认为具有细胞毒性，是AD和T2D发病的原因。因此，抑制淀粉样多肽聚集和解聚现有的淀粉样聚集体是治疗和预防这两种疾病的有前景的方法。因此，在本研究中，我们通过进行构效关系研究并确定活性位点，评估了A型原花青素及其亚结构和对Aβ/hIAPP的抗聚集和解聚活性。采用硫黄素-T（Th-T）测定法（基于荧光强度定量淀粉样多肽的聚集程度）和透射电子显微镜（TEM）（用于直接观察淀粉样多肽）来评估活性。结果表明，含儿茶酚的化合物表现出Aβ/hIAPP抗聚集和解聚活性，而不含儿茶酚的化合物没有活性。这表明儿茶酚的存在对这两种活性都很重要。日常摄入含有A型原花青素的食物可能对预防和治疗这两种疾病有效。
