Polyphenols from Trapa bispinosa Roxb. pericarp extract with inhibitory activities against amyloid-β aggregation and acetylcholinesterase

This study focused on the isolation and structural characterization of three known galloyl glucoses (1, 3, and 4) and a new monomeric ellagitannin, trabisnin (16), from the Trapa bispinosa Roxb. pericarp extract (TBPE). The extract was rich in hydrolyzable tannins, including ellagitannins and gallotannins, along with other polyphenols. The structure of compound 16 was elucidated as an ellagitannin bearing a brevifolincarboxyloyl group based on comprehensive spectroscopic analyses—1D and 2D nuclear magnetic resonance, electrospray ionization mass spectrometry—and supporting chemical evidence. To explore the potential of polyphenols in TBPE for the prevention or treatment of Alzheimer’s disease (AD), the inhibitory activities of TBPE polyphenols and related compounds, including hydrolyzable tannin metabolites, against amyloid-β (Aβ) aggregation and acetylcholinesterase (AChE) were also investigated. Among the tested compounds, 1,2,4,6-tetra-O-galloyl-β-D-glucose (10), 1,2,3,4,6-penta-O-galloyl-β-D-glucose (11), tellimagrandin II (13), eschweilenol A (18), rubuphenol (19), and valoneic acid dilactone (20) exhibited strong inhibitory effects on both Aβ aggregation and AChE. Among the metabolites of hydrolyzable tannins, gallic acid (21) and urolithin A (25) showed the most potent inhibition of Aβ aggregation and AChE, respectively. Kinetic analyses using Lineweaver–Burk plots revealed that compounds 11 and 13 act as mixed-type AChE inhibitors, whereas compound 20 exhibits competitive inhibition. These findings suggest that TBPE polyphenols may serve as promising functional ingredients for the prevention or management of AD.