This study is the first report that shows that DE extract and donepezil inhibit BChE and BACE-1 synergistically and/or additively, indicating a prospective role for DE extract in the treatment of AD when combined with donepezil through multi-targeted therapies (cholinergic hypothesis via BChE and amyloid peptide pathway via BACE-1). This evidence concerns the gene BACE1 and Alzheimer disease.