(‒)-Pteroside N and pterosinone, new BACE1 and cholinesterase inhibitors from Pteridium aquilinum

Bioassay-guided fractionation of the ethanolic extract from the whole plants of Pteridium aquilinum has resulted in the isolation of a new pterosin glycoside, (‒)-pteroside N (1), and a new seco-illudoid sesquiterpene, pterosinone (2). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for the anti-Alzheimer disease (anti-AD) activity through enzyme inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). (‒)-Pteroside N (1) showed moderate BACE1 inhibitory activity (IC₅₀ value: 30.6 μM), but exhibited potent inhibitory activity against AChE and BChE (IC₅₀ values: 4.47 and 7.39 μM, respectively). On the other hand, pterosinone (2) showed mild AChE and BChE inhibitory activity (IC₅₀ value: 87.7 and 72.9 μM), but exhibited potent inhibitory activity against BACE1 (IC₅₀ value: 19.4 μM). The results of the present study demonstrate that sesquiterpenoids from P. aquilinum might be beneficial in the treatment of AD.