• Md Yousof Ali, Su Hui Seong, Hyun Ah Jung, Susoma Jannat, and Jae Sue Choi.
• Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
• Arch Pharm Res. 2018 Jul 1; 41 (7): 753-764.

AbstractIn 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 β-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 µM for AChE, 5.78-13.91 µM for BChE, and 1.99-17.34 µM 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.

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