Evaluation of butyrylcholinesterase inhibitory activity by chlorogenic acids and coffee extracts assed in ITC and docking simulation models.

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.