Systematic analysis on the mechanism for suppressing amyloid β42 aggregation by several constituents of food and herbal medicine

Kazuma Murakami, Kazuhiro Irie

Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University

Numerous natural products exhibit suppressive activity against amyloid β42 (Aβ42) aggregation, but their mode of action remains to be fully elucidated. We proposed three structural characteristics of several constituents of food and herbal medicine required for the suppression of Aβ42 aggregation by targeting specific amino acid residues:(1)catechol-type flavonoids could form Michael adducts with the side chains of Lys16 and/or 28 through their autoxidation;(2)non-catechol-type flavonoids with planarity due to α, β-unsaturated carbonyl groups can interact with the intermolecular β-sheet region in Aβ42 oligomers, especially with aromatic rings (Phe19 and 20);(3)carboxylic acid derivatives with triterpenoid and phenolic moieties could form a salt bridge with basic amino acid residues in Aβ42, as exemplified in uncarinic acids.

Address correspondence to Dr. Kazuhiro Irie, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University (Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan)