Antihypertensive Activity of Arabica Coffee Husks (Cascara) using Metabolomic Profiling and Molecular Docking
DOI:
https://doi.org/10.25186/.v21i.2408Abstract
Green coffee beans have been reported to lower blood pressure, and compounds derived from cascara arabica have shown potential anti-hypertensive activity. In this study, we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of these compounds and identified potential ACE inhibitors through metabolomic profiling and molecular docking analysis. Metabolomic data were processed using chemometric analysis, followed by molecular docking to assess the binding interactions of the compounds with the active site residues of the ACE and AGTR1 enzymes. LC-HRMS revealed that cascara arabica contained primarily caffeine, neochlorogenic acid, protocatechuic acid, caffeic acid, trans-caffeic acid, chlorogenic acid, and gallic acid. The docking results revealed the strongest binding site residues for quercetin-3β-D-glucoside, as well as for other docked compounds, including kaempferol, chlorogenic acid (5-CQA), neochlorogenic acid, gallic acid, and caffeic acid, which all exhibited good binding affinities with proteins 1O86 and 4ZUD. The activity of compounds was better than that of captopril, which was used as a positive control. The validation method of molecular docking was based on an RMSD value <2.00 Å for native ligand redocking, with RMSD values of 0.45 Å for the lisinopril ligand and 1.92 Å for the olmesartan ligand. Binding affinity scores for ACE protein controls were captopril at –5.50 Å and lisinopril at –8.10 Å, whereas for AGTR1 protein controls, candesartan was –8.90 Å and olmesartan was –9.80 Å. Results showed that the compounds from cascara arabica could be serve as an initial benchmark in determining potential drug compounds.
Key words: Angiotensin; agtr1; captopril; chlorogenic acid; caffeic acid.
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