Effect of Meroterpenoids from Sargassum macrocarpum on the Inhibition of Amyloid Polypeptide Aggregation

Amyloid polypeptide aggregation is considered one of the factors involved in the pathogenesis of Alzheimer’s disease (AD) and type 2 diabetes (T2D), and the number of affected patients increases as the population ages. Amyloid β (Aβ) found in the brain of patients with AD and human islet amyloid polypeptide (hIAPP) found in the pancreas of patients with T2D are thought to be cytotoxic during the aggregation process, especially the low-molecular-weight oligomers that are aggregation intermediates. In this study, meroterpenoids isolated and structurally determined from the brown alga Sargassum macrocarpum were evaluated for their ability to inhibit hIAPP aggregation. The results showed that 16 compounds from S. macrocarpum exhibited hIAPP aggregation–inhibitory activity, mainly through the inhibition of fiber elongation. These compounds showed higher activity with a hydroquinone moiety than with a quinone moiety, similar to their aggregation–inhibitory activity against Aβ42. Furthermore, these peptides demonstrated the potential to inhibit oligomer formation at high concentration ratios of 1 : 4 or higher. Further, compounds lacking hydroxyl groups did not exhibit this aggregation–inhibitory activity, suggesting that the phenolic hydroxyl group is essential for this activity.