Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Poland.
Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Poland.
Food Res Int. 2018 Jul;109:268-277. doi: 10.1016/j.foodres.2018.04.041. Epub 2018 Apr 21.
In patients with Alzheimer's disease (AD), elevated levels of butyrylcholinesterase (BChE) are observed. The enzyme hydrolyses acetylcholine, which shows deficiency in these patients. Therefore, BChE inhibitors are used in the treatment of Alzheimer's disease, especially synthetic ones, showing side effects with long-term intake. The sources of natural BChE inhibitors are constantly being sought. Coffee brews have been shown to reduce the symptoms of AD in epidemiological studies. However, the ability to inhibit BChE activity has not been investigated, depending on the degree of coffee roasting. The study was aimed at determining the interactions between BChE and the bioactive compounds of coffee and their ability to inhibit the activity of BChE. A comparison of individual bioactive compounds of coffee as well as extracts obtained from two main species, Arabica and Robusta, and additionally from different degrees of roasting was made. Two models were used: isothermal titration calorimetry (ITC) and molecular docking simulation. ITC analysis showed strong interactions of ferulic and dihydrocaffeic acids with BChE. These compounds are the metabolites of the chlorogenic acids, including both mono- and diesters of caffeic acid with quinic acid. Docking simulation showed their strong hydrophobic interaction with BChE, stabilized by hydrogen bonds and pi-pi interactions. After introducing acetylcholine into the model system, the strongest ability to inhibit hydrolytic activity of BChE was again observed for ferulic acid and additionally for 3-caffeoylquinic acid, and among coffee brews the most active were light roasted Arabica and green Robusta. The study was based on the physiological concentrations of coffee components, so the potential therapeutic effect of coffee infusions was proved.
在阿尔茨海默病（AD）患者中，观察到丁酰胆碱酯酶（BChE）水平升高。该酶水解乙酰胆碱，而这些患者体内的乙酰胆碱则缺乏。因此，BChE 抑制剂被用于治疗阿尔茨海默病，尤其是合成抑制剂，长期摄入会产生副作用。人们一直在不断寻找天然 BChE 抑制剂的来源。流行病学研究表明，咖啡冲泡物可以减轻 AD 的症状。然而，其抑制 BChE 活性的能力尚未根据咖啡烘焙程度进行研究。本研究旨在确定 BChE 与咖啡生物活性化合物之间的相互作用及其抑制 BChE 活性的能力。对咖啡的各个生物活性化合物以及从两个主要品种（阿拉比卡和罗布斯塔）以及不同烘焙程度获得的提取物进行了比较。使用了两种模型：等温滴定量热法（ITC）和分子对接模拟。ITC 分析表明，阿魏酸和二氢咖啡酸与 BChE 具有强烈的相互作用。这些化合物是绿原酸的代谢物，包括咖啡酸的单酯和二酯与奎尼酸。对接模拟表明，它们与 BChE 具有强烈的疏水性相互作用，由氢键和π-π相互作用稳定。在向模型系统中引入乙酰胆碱后，再次观察到阿魏酸和 3-咖啡酰奎宁酸对 BChE 水解活性具有最强的抑制能力，而在咖啡冲泡物中，轻度烘焙的阿拉比卡和绿色罗布斯塔最为活跃。该研究基于咖啡成分的生理浓度，因此证明了咖啡浸液的潜在治疗效果。
