Liquidambaric acid as a non-competitive α-glucosidase inhibitor: multi-level evidence from enzyme kinetics, molecular docking, molecular dynamics simulations, and a Drosophila hyperglycaemic model.

Abstract

Liquidambaric acid, a pentacyclic triterpenoid from Liquidambar formosana Hance, was evaluated as a novel α-glucosidase inhibitor for type 2 diabetes mellitus (T2DM) management. Enzyme kinetic assays revealed its potent non-competitive inhibition (IC₅₀ = 0.12 mM). Molecular docking showed stable hydrogen bonding at an allosteric site, altering enzyme conformation, while 100 ns molecular dynamics (MD) simulations confirmed the stability of the protein-ligand complex. In vivo, a Drosophila melanogaster hyperglycaemic model demonstrated significant glucose reduction, confirming its hypoglycaemic potential. ADMET analysis predicted favourable bioavailability and low toxicity, supporting its development as a safe therapeutic agent. These findings integrate enzyme kinetics, molecular modelling, MD simulations, and in vivo validation, highlighting liquidambaric acid's potential as a multifunctional and cost-effective agent for T2DM management.