Dual‐Activity Phenolic Extracts from Mallotus nanus : Acetylcholinesterase Inhibition, Antioxidant Properties, and In Silico Insights

ABSTRACT Mallotus nanus , a traditional Vietnamese medicinal plant, was investigated as a potential source of bioactive phenolic exhibiting acetylcholinesterase (AChE) inhibition and antioxidant properties by using combined in vitro and in silico approaches. Ethanolic extracts from the leaf, stem, and root were tested for antioxidant capacity (DPPH, ABTS, and FRAP assays) and AChE inhibition (Ellman's method). Among them, the leaf extract showed the highest activity, with moderate AChE inhibition (IC 50 = 409.45 ± 5.22 µg/mL) and notable antioxidant capacity (DPPH IC 50 = 68.23 ± 0.34 µg/mL; ABTS IC 50 = 44.06 ± 0.34 µg/mL). UHPLC analysis identified eight major phenolic constituents, seven reported for the first time in M. nanus , including gallic acid, catechin, epigallocatechin gallate (EGCG), caffeine, rutin, ellagic acid, and quercetin. Molecular docking suggested favorable binding of rutin and EGCG to AChE, with rutin ( A5 ; CNN affinity: 6.56) showing a higher docking score than the reference inhibitor donepezil (E2020). Molecular dynamics simulation (MD) confirmed stable ligand–AChE interactions. These findings indicate that M. nanus leaf extract contains phenolic components with combined antioxidant activity and moderate AChE inhibition, supporting its potential as a natural source of compounds for further fractionation and biological studies related to neurodegenerative disorders.