Anti-Alzheimer’s disease activity of compounds from the root bark of Morus alba L

The inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β -site amyloid precursor protein cleaving enzyme 1 (BACE1) plays important roles in prevention and treatment of Alzheimer’s disease (AD). Among the individual parts of Morus alba L. including root bark, branches, leaves, and fruits, the root bark showed the most potent enzyme inhibitory activities. Therefore, the aim of this study was to evaluate the anti-AD activity of the M. alba root bark and its isolate compounds, including mulberrofuran G ( 1 ), albanol B ( 2 ), and kuwanon G ( 3 ) via inhibition of AChE, BChE, and BACE1. Compounds 1 and 2 showed strong AChE- and BChE-inhibitory activities; 1 – 3 showed significant BACE1 inhibitory activity. Based on the kinetic study with AChE and BChE, 2 and 3 showed noncompetitive-type inhibition; 1 showed mixed-type inhibition. Moreover, 1 – 3 showed mixed-type inhibition against BACE1. The molecular docking simulations of 1 – 3 demonstrated negative binding energies, indicating a high affinity to AChE and BACE1. The hydroxyl group of 1 – 3 formed hydrogen bond with the amino acid residues located at AChE and BACE1. Consequently, these results indicate that the root bark of M. alba and its active compounds might be promising candidates for preventive and therapeutic agents for AD.