摘要：Among 276 herbal extracts, a methanol extract of
Castanopsis cuspidata var.
sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities against butyrylcholinesterase (BChE), monoamine oxidases (MAOs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were also evaluated. Of these compounds, 4′-
O-(α-
l-rhamnopyranosyl)-3,3′,4-tri-
O-methylellagic acid (
3) and 3,3′,4-tri-
O-methylellagic acid (
4) effectively inhibited AChE with IC
50 values of 10.1 and 10.7 µM, respectively. Ellagic acid (
5) inhibited AChE (IC
50 = 41.7 µM) less than
3 and
4. In addition,
3 effectively inhibited MAO-B (IC
50 = 7.27 µM) followed by
5 (IC
50 = 9.21 µM). All five compounds weakly inhibited BChE and BACE-1. Compounds
3,
4, and
5 reversibly and competitively inhibited AChE, and were slightly or non-toxic to MDCK cells. The binding energies of
3 and
4 (− 8.5 and − 9.2 kcal/mol, respectively) for AChE were greater than that of
5 (− 8.3 kcal/mol), and
3 and
4 formed a hydrogen bond with Tyr124 in AChE. These results suggest
3 is a dual-targeting inhibitor of AChE and MAO-B, and that these compounds should be viewed as potential therapeutics for the treatment of Alzheimer’s disease.
