Interaction of the Coffee Diterpenes Cafestol and 16-O-Methyl-Cafestol Palmitates with Serum Albumins

Abstract

The main coffee diterpenes cafestol, kahweol, and 16-O-methylcafestol, present in the bean lipid fraction, are mostly esterified with fatty acids. They are believed to induce dyslipidaemia and hypercholesterolemia when taken with certain types of coffee brews. The study of their binding to serum albumins could help explain their interactions with biologically active xenobiotics. We investigated the interactions occurring between cafestol and 16-O-methylcafestol palmitates with Bovine Serum Albumin (BSA), Human Serum Albumin (HSA), and Fatty Free Human Serum Albumin (ffHSA) by means of circular dichroism and fluorimetry. Circular Dichroism (CD) revealed a slight change (up to 3%) in the secondary structure of fatty-free human albumin in the presence of the diterpene esters, suggesting that the aliphatic chain of the palmitate partly occupies one of the fatty acid sites of the protein. A warfarin displacement experiment was performed to identify the binding site, which is probably close but not coincident with Sudlow site I, as the affinity for warfarin is enhanced. Fluorescence quenching titrations revealed a complex behaviour, with Stern–Volmer constants in the order of 103–104 Lmol−1. A model of the HSA-warfarin-cafestol palmitate complex was obtained by docking, and the most favourable solution was found with the terpene palmitate chain inside the FA4 fatty acid site and the cafestol moiety fronting warfarin at the interface with site I.

On the Cholesterol Raising Effect of Coffee Diterpenes Cafestol and 16-O-Methylcafestol: Interaction with Farnesoid X Receptor

“…Fluorescence data were analyzed using ExcelTM (Microsoft OfficeTM) and Veusz ( ). Slight inner filter effects in the titration with the diterpenes were observed due to their modest absorbance at 280 nm and were corrected according to our previous studies on the interactions of diterpenes with albumins [ 43 ]. Conversely, quenching data for the titrations with GW4064 and GG were not corrected for inner filter, as the aim was to replicate and compare the behavior of our expressed proteins with the literature data of Yang et al [ 39 ] which are apparently not corrected for inner filter.…”

New Diterpenes with Potential Antitumoral Activity Isolated from Plants in the Years 2017–2022

“…Robusta), have been extensively studied. Among the many compounds identified, there are three important diterpenes, such as cafestol, 16-Omethylcafestol and kahweol, which belong to the kaurene family [114], that have several biological activities [115,116]. In particular, 16-O-methylcafestol is considered a marker of the species Coffea canephora [117].…”

Coffee and Lower Risk of Type 2 Diabetes: Arguments for a Causal Relationship

“…Even at these low concentrations, coffee phytochemicals and their metabolites interact with many components of cells and organs. Cellular targets for physical binding of phytochemicals include the complex of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associating protein-1 (Keap1) [ 68 , 69 , 70 , 71 ], the aryl hydrocarbon receptor (AHR) [ 72 , 73 , 74 , 75 ], protein disulfide isomerase3 [ 76 ], 3-hydroxy-3-methylglutaryl-coenzyme A reductase [ 77 ], protein kinase B (AKT) [ 78 ], glutathione S-transferase pi isoform-1 [ 79 ], vascular endothelial growth factor receptor [ 80 ], PPARγ [ 81 ], amyloid forming peptides [ 55 , 82 , 83 , 84 , 85 , 86 , 87 ], basic proline-rich protein in saliva [ 88 ], human serum albumin [ 89 , 90 ] or low density lipoprotein [ 91 ].…”