Amyloid Polypeptide Disaggregation Activity of Passion Fruit Seed-Derived Polyphenol Compounds

Abstract

In an aging society, the prevalence of Alzheimer disease (AD) and type 2 diabetes (T2D) has increased. It is currently hypothesized that these diseases are caused by the aggregation of amyloid β (Aβ) in the brain and human islet amyloid polypeptide (hIAPP) in the islets of Langerhans, respectively. Therefore, the disaggregation of these existing amyloid aggregates is a promising approach to the prevention and treatment of both diseases. In our previous studies, we found a remarkable Aβ and hIAPP aggregation inhibitory activity of polyphenolic compounds containing catechol moieties. Compared to previous reports on their aggregation inhibitory activity, there are few on the disaggregation activity of polyphenolic compounds. Additionally, there are few findings on the disaggregation activity of polyphenolic compounds on hIAPP. In this study, we investigated the Aβ and hIAPP disaggregation activity of scirpusin B, a polyphenolic compound found in passion fruit seeds, and related compounds. Thioflavin T (Th-T) assays and transmission electron microscopy (TEM) were performed on these compounds to evaluate their Aβ42 and hIAPP disaggregation activities. The results showed that scirpusin B and its related compounds showed remarkable disaggregation activity. The structure–activity relationship of these compounds revealed that the presence of catechol moieties is important for this activity. This study also showed that polyphenols from passion fruit seeds have significant disaggregation activity against amyloid polypeptide aggregation.