1. Anti-Alzheimer’s disease activity of compounds from the root bark of Morus alba L
- Author
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Hee Sook Sohn, A Ra Jo, Su Hui Seong, Anupom Roy, Seo In Oh, Eun Bi Kuk, Hyun Ah Jung, and Jae Sue Choi
- Subjects
Models, Molecular ,0301 basic medicine ,Aché ,Plant Roots ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,mental disorders ,Drug Discovery ,Amyloid precursor protein ,Aspartic Acid Endopeptidases ,Amino Acids ,Butyrylcholinesterase ,Mulberrofuran G ,chemistry.chemical_classification ,Anti alzheimer ,biology ,Plant Extracts ,Chemistry ,Organic Chemistry ,Hydrogen Bonding ,Acetylcholinesterase ,language.human_language ,Molecular Docking Simulation ,Kinetics ,030104 developmental biology ,Enzyme ,Biochemistry ,visual_art ,Plant Bark ,visual_art.visual_art_medium ,biology.protein ,language ,Molecular Medicine ,Bark ,Cholinesterase Inhibitors ,Morus ,Amyloid Precursor Protein Secretases ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2017