| dc.description.abstract | Cardiac fibrosis remains as the leading cause of death worldwide and is often associated
with elevated levels of transforming growth factor-β 1 (TGF-β1) and galectin-3, making
them potential therapeutic targets. Recent studies revealed that quercetin, myricetin, and
kaempferol have the biological effect for several cardiovascular diseases. However, the
investigation into this topic through molecular models and analysis remain unexplored.
The aim of this study was to evaluate the potential effect of quercetin, myricetin, and
kaempferol which targeted TGF-β1 and galectin-3. In this study, quercetin, myricetin, and
kaempferol roled as the tested ligands. Subsequently, colchicine and native ligand acted
as control ligands that were screened through molecular docking against TGF-β1 and
galectin-3 using AutoDock tools to identify the potential inhibitor. The stability of ligandreceptor complexes was assessed through molecular dynamic (MD) simulations using
NMAD. Absorption, Distribution, Metabolism, Excretion and toxicity (ADMET)
prediction were also performed using ADMETlab 2.0. Molecular docking analysis revealed
that quercetin, myricetin, and kaempferol exhibited strong binding affinity which are -8.9
kcal/mol, -8.5 kcal/mol, -7.6 kcal/mol respectively with TGF-β1, and -7.5 kcal/mol, -7.0
kcal/mol, -5.7 kcal/mol respectively with galetcin-3; low inhibition constant (Ki); and
stable interaction with the active sites of TGF-β1 and galectin-3. MD simulations
confirmed the stability and compactness of the ligand-receptor complexes. ADMET
analysis also showed high Plasma Protein Binding (PPB) values (quercetin: 95%,
myricetin: 92%, and kaempferol: 97%) and moderate clearance values (quercetin: 8.284%,
myricetin, and 7.716%, kaempferol: 6.868%) for the tested compounds. In conclusion, the
in silico analyses suggested that quercetin, myricetin, and kaempferol are promising for
cardiac fibrosis therapies by inhibiting TGF-β1 and galectin-3 | en_US |
