Detection of Dietary Chalcone and Flavonoid Metabolites in Mice Using UPLC-MS/MS and Their Modulatory Effects on Amyloid ß Aggregation.

Amyloid ß-protein (Aß42) aggregates have been demonstrated to induce cognitive decline and neurodegeneration in Alzheimer's disease (AD). Thus, functional food ingredients that inhibit Aß42 aggregation are valuable for AD prevention. Although several food ingredients have been studied for their anti-aggregation activity, information on their bioavailability in the brain, incorporated forms, and relevance to AD etiology is limited. Here, we first detected the sulfate- and glucuronic-acid-conjugated forms of green perilla-derived chalcone (1) and taxifolin (2), which inhibit Aß42 aggregation, in the brain, small intestine, and plasma of mice (1 and 2 were administered orally) using ultra-performance liquid chromatography-tandem mass spectrometry. We observed that the conjugated metabolites (sulfate (4) and glucuronide (5)) of 1 prevented the fibrillization and oligomerization of Aß42. These findings imply that the conjugated metabolites of 1 can prove beneficial for AD treatment.