Kuk Eun Bi, Jo A Ra, Oh Seo In, Sohn Hee Sook, Seong Su Hui, Roy Anupom, Choi Jae Sue, Jung Hyun Ah
Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 54896, Republic of Korea.
Department of Food Science and Nutrition, Pukyong National University, Busan, 48513, Republic of Korea.
Arch Pharm Res. 2017 Mar;40(3):338-349. doi: 10.1007/s12272-017-0891-4. Epub 2017 Jan 16.
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.
抑制乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）和β-位点淀粉样前体蛋白裂解酶1（BACE1）在阿尔茨海默病（AD）的预防和治疗中发挥着重要作用。在桑树（Morus alba L.）的各个部分，包括根皮、树枝、树叶和果实中，根皮显示出最强的酶抑制活性。因此，本研究的目的是通过抑制AChE、BChE和BACE1来评估桑树根皮及其分离化合物，包括桑呋喃G（1）、阿尔巴醇B（2）和桑酮G（3）的抗AD活性。化合物1和2表现出较强的AChE和BChE抑制活性；1-3表现出显著的BACE1抑制活性。基于对AChE和BChE的动力学研究，2和3表现出非竞争性抑制；1表现出混合型抑制。此外，1-3对BACE1表现出混合型抑制。1-3的分子对接模拟显示出负结合能，表明对AChE和BACE1具有高亲和力。1-3的羟基与位于AChE和BACE1的氨基酸残基形成氢键。因此，这些结果表明，桑树的根皮及其活性化合物可能是AD预防和治疗药物的有前途的候选者。
