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 IC50 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 IC50 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.