Phenylpropanoids and lignans from Prunus tomentosa seeds as efficient β-amyloid (Aβ) aggregation inhibitors

Alzheimer's disease (AD) is characterized by the progressive accumulation of extracellular β-amyloid (Aβ) aggregates. Recently, lignans and phenylpropanoids are attracting increasing attention to discovery useful agents of inhibition on Aβ aggregation. In the present study, to develop potential agents for slowing the progression of AD, Prunus tomentosa seeds were selected as a raw material for bioactive compounds, which led to the separation of two pairs of new enantiomeric lignans and phenylpropanoids using chiral HPLC. The planar structures of these compounds were elucidated by spectroscopic data analyses. And their absolute configurations were determined by comparing of experimental and calculated electronic circular dichroism (ECD). The biosynthesis pathway was also discussed. Additionally, the inhibitory activity on Aβ aggregation of all optical pure compounds was tested by thioflavin T (ThT) assay. The isolates (1a, 1b, 2a and 2b) showed more potent inhibitory activity than positive control curcumin with inhibitory rate of 73.89 ± 3.41% 78.69 ± 1.50%, 63.25 ± 2.68%, and 67.13 ± 0.90% at 20 μM, respectively. More importantly, the inhibition profiles were explained by molecular dynamics and docking simulation studies.