Ali_2018_Arch.Pharm.Res_41_753

In the present study, we investigated the anti-Alzheimer's disease (AD) potential of six dihydroxanthyletin-type coumarins, 4'-hydroxy Pd-C-III (1), decursidin (2), Pd-C-I (3), 4'-methoxy Pd-C-I (4), Pd-C-II (5), and Pd-C-III (6) from Angelica decursiva by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). Coumarins 1-6 exhibited dose-dependent inhibition of AChE, BChE, and BACE1. IC50 values were 1.0-4.01 microM for AChE, 5.78-13.91 microM for BChE, and 1.99-17.34 microM for BACE1. Kinetic studies revealed that 1 was noncompetitive inhibitor for AChE, while 2-6 were mixed-type inhibitors of AChE. Compounds 1, 5 and 6 had mixed-type inhibitory effects against BChE; 2 was a competitive inhibitor; and 3 and 4 were noncompetitive inhibitors. Against BACE1, compounds 1, 2, 3, 5 showed mixed-type inhibition and 4, 6 were noncompetitive inhibitors. Molecular docking simulation of the compounds demonstrated negative-binding energies indicating high proximity to the active site and tight binding to the enzyme. These data suggested that the compounds inhibited AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for AD treatment.