评估乙酰胆碱酯酶结合与胃肠道消化的咖啡及咖啡馏分中生物活性化合物的相互作用。

Assessment of the Interaction of Acetylcholinesterase Binding with Bioactive Compounds from Coffee and Coffee Fractions Digested in the Gastrointestinal Tract.

作者信息

Grzelczyk Joanna, Pérez-Sánchez Horacio, Carmena-Bargueño Miguel, Rodríguez-Martínez Alejandro, Budryn Grażyna

机构信息

Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Lodz 90-537, Poland.

Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Guadalupe, Murcia 30107, Spain.

出版信息

J Agric Food Chem. 2024 Oct 4;72(41):22776-97. doi: 10.1021/acs.jafc.4c05435.

The aim of the study was to evaluate the degree of acetylcholinesterase (AChE) inhibition by green and light- and dark-roasted coffee extracts and their fractions after digestion in a simulated gastrointestinal tract. The analysis was carried out using isothermal titration calorimetry, molecular docking, and dynamics simulations. The results showed that 3--caffeoylquinic acid binds strongly to AChE through hydrogen interactions with the amino acids ARG289A, HIS440A, and PHE288A and hydrophobic interactions with TYR121A in the active site of the enzyme. The Robusta green coffee extract (Δ = -35.87 kJ/mol) and dichlorogenic acid fraction (Δ = -19-29 kJ/mol) showed the highest affinity. Dichlorogenic acids (3,4--dicaffeoylquinic acid, 4,5--dicaffeoylquinic acid, and 3,4--dicaffeoylquinic acid) have high affinity for AChE as single compounds (Δ(ITC) = -48.99-55.36 kJ/mol, Δ(LF/AD) = -43.38-45.38 kJ/mol). The concentration necessary to reduce AChE activity by 50% amounted to 0.22 μmol/μmol chlorogenic acids to the enzyme.

该研究的目的是评估生咖啡、浅度烘焙咖啡和深度烘焙咖啡提取物及其在模拟胃肠道消化后的馏分对乙酰胆碱酯酶（AChE）的抑制程度。分析采用等温滴定量热法、分子对接和动力学模拟进行。结果表明，3 - 咖啡酰奎尼酸通过与酶活性位点的氨基酸ARG289A、HIS440A和PHE288A的氢键相互作用以及与TYR121A的疏水相互作用，与AChE强烈结合。罗布斯塔生咖啡提取物（Δ = -35.87 kJ/mol）和二咖啡酰奎尼酸馏分（Δ = -19 - 29 kJ/mol）表现出最高的亲和力。二咖啡酰奎尼酸（3,4 - 二咖啡酰奎尼酸、4,5 - 二咖啡酰奎尼酸和3,4 - 二咖啡酰奎尼酸）作为单一化合物对AChE具有高亲和力（Δ(ITC) = -48.99 - 55.36 kJ/mol，Δ(LF/AD) = -43.38 - 45.38 kJ/mol）。使AChE活性降低50%所需的浓度为每微摩尔酶0.22微摩尔绿原酸。