BACE1 inhibitory potential: screening of medicinal plants collected from Nepal high altitude regions

Abstract Fifty-four plant extracts from thirty-two medicinal plants collected in Nepal were evaluated for their inhibitory potential against the enzyme beta-secretase-1 (BACE1), to identify potential therapeutic agents for Alzheimer’s disease (AD). Of the studied extracts, rhizome extract of Rheum australe D. Don showed the highest inhibitory potential, with an IC 50 value of 0.872 ± 0.006 µg/mL. After BACE1 inhibitory activity check using 9 fractions collected from Prep-HPLC, further profiling of the metabolites of the best fraction 7 was performed using high-resolution mass spectrometry (HRMS). Results revealed the presence of diverse secondary metabolites, including aloe-emodin-8-O-β-D-glucoside, rhein-8-O-glucoside, piceatannol-3’-O-β-D-glucoside, emodin-8-glucoside, physcion 8-O-β-D-glucoside, desoxyrhaponticin, chrysophanol-8-O-glucoside, rhapontigenin, rhein, desoxyrhapontigenin, piceatannol, chrysophanol, physcion, and aloe-emodin. In-silico docking simulations were performed to identify potent compounds with high binding efficiencies to BACE1. Compound picetannol-3’-O-β-D-glucoside showed the best binding energy (-53.494 kcal/mol) and inhibitory potential with an IC 50 value of 1.270 ± 0.130 µM for BACE1. These results suggested that the R. australe D. Don extract is a promising agent for the treatment of AD.