In Silico Study of Green Tea and Green Coffee Compounds Inhibiting Cardiac Fibrosis in Metabolic Syndrome Via Dual Inhibition FGF23/FGFR4

Abstract

Cardiac fibrosis can occur due to various causes, including metabolic syndrome. Increased expression of FGF23, which can activate the cardiac fibrosis pathway via FGFR4, is often observed in metabolic syndrome. Meanwhile, inhibitor therapies targeting FGF23 and FGFR4 for cardiac fibrosis are minimal. Therefore, this study used green tea and coffee compounds to determine their potential as specific inhibitors of FGF23 and FGFR4 to inhibit cardiac fibrosis signaling using bioinformatics methods. Six compounds derived from green tea and coffee—cafestol, CGA, ECG, EGC, EGCG, and Kahweol—were evaluated through ADMET screening, membrane permeability prediction, toxicity prediction, molecular docking, and molecular dynamics simulations. The analysis revealed that all six compounds could pass through the phospholipid membrane, with cafestol having the lowest energy transfer value. Molecular docking and molecular dynamics analyses of FGF23 showed that cafestol and kahweol compounds had better binding affinity values (-6.2 and -5.9 kcal/mol) ​​than the control and showed stable ligand stability and movement (~3 Å). Meanwhile, all compounds had good binding affinity and succeeded in occupying more active sites on FGFR4, with EGC, EGCG, and kahweol compounds showing the most stable stability and movement compared to other compounds against the native ligand (~3 Å). This study demonstrates that the six compounds derived from green tea and coffee have strong potential as specific inhibitors of FGF23 and FGFR4 to inhibit cardiac fibrosis signaling in metabolic syndrome conditions.