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Effect of Meroterpenoids from Sargassum macrocarpum on the Inhibition of Amyloid Polypeptide Aggregation
Yuta Tozawa1, Seiya Shinoda2, Mitsuhiro Sekiguchi2
1Graduate School of Science and Technology, University of Tsukuba.
Abstract:
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.
Insights
Brown algae compounds inhibit amyloid aggregation linked to Alzheimer's and diabetes. These meroterpenoids, particularly those with hydroquinone structures, show potential in preventing toxic oligomer formation.
Area of Science:
- Marine natural products chemistry
- Biochemistry
- Neuroscience
- Endocrinology
Background:
- Amyloid polypeptide aggregation is implicated in Alzheimer's disease (AD) and type 2 diabetes (T2D) pathogenesis.
- Amyloid β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregation, especially oligomer formation, are cytotoxic.
- Aging populations are increasing the prevalence of AD and T2D.
Purpose of the Study:
- To investigate the potential of meroterpenoids from the brown alga Sargassum macrocarpum to inhibit hIAPP aggregation.
- To identify structural features of these compounds that contribute to their inhibitory activity.
Main Methods:
- Isolation and structural determination of meroterpenoids from Sargassum macrocarpum.
- In vitro evaluation of isolated compounds for their ability to inhibit hIAPP aggregation.
- Analysis of structure-activity relationships, focusing on moieties and hydroxyl group presence.
Main Results:
- Sixteen compounds from S. macrocarpum demonstrated hIAPP aggregation-inhibitory activity, primarily by inhibiting fiber elongation.
- Compounds with a hydroquinone moiety exhibited higher activity than those with a quinone moiety, similar to observed Aβ42 inhibition.
- Oligomer formation was inhibited at high concentration ratios (≥1:4).
- Compounds lacking hydroxyl groups showed no aggregation-inhibitory activity, highlighting the importance of the phenolic hydroxyl group.
Conclusions:
- Meroterpenoids from Sargassum macrocarpum possess significant hIAPP aggregation-inhibitory properties.
- The hydroquinone moiety and phenolic hydroxyl groups are crucial for the observed anti-amyloidogenic activity.
- These findings suggest potential therapeutic leads for AD and T2D derived from marine natural products.
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