Comparative Study of Aβ Aggregation Inhibitors of Yamamomiji (Acer amoenum var. matsumurae) Red and Green Leaf Extracts with Isolation of Active Compound

Alzheimer’s disease (AD) is a brain disorder associated with amyloid beta (Aβ) aggregation, leading to neuronal damage and faster disease progression. The aggregation-inhibiting compounds are necessary to prevent and treat AD. Acer species are rich in phenolic compounds and possess diverse biological activities. In this study, we investigated the Aβ42 aggregation inhibitory activity of the understudied species, Acer amoenum var. matsumurae red and green leaf extracts, using thioflavin T and also monitored 24-h Aβ42 aggregation kinetics. The red leaf extract showed the strongest inhibition (half-maximal effective concentration [EC50] = 1.28 mg/mL), and the green leaf extract showed moderate inhibition (EC50 = 8.61 mg/mL). In addition, the time-course profile of Aβ42 aggregation at a concentration of 75 µg/mL was performed. The red leaf extract indicated strong inhibition in the Aβ42 fibril formation when compared to the green leaf extract and was analyzed by fitting the experimental data to an empirical sigmoidal function (logistic function). The red leaf exhibited significantly stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 = 2.81 µg/mL) compared to the green leaf (IC50 = 6.27 µg/mL). The red leaf extract exhibited greater monomeric anthocyanin content than the green leaf extract, as determined by the pH-differential method. The active compound was isolated and identified by using chromatographic and spectroscopic techniques. These results suggest that A. amoenum var. matsumurae red leaf extract and the active compound epicatechin may prove to be Aβ aggregation inhibitors to prevent or delay AD progression.