The inhibitory mechanism of pentacyclic triterpenoid acids on pancreatic lipase and cholesterol esterase

Inhibiting pancreatic Lipase (PL) and cholesterol esterase (CEase) can effectively control blood triglycerides and cholesterol levels. The interaction characteristics of pentacyclic triterpenoid acids (oleanolic acid [OA], ursolic acid [UA], and corosolic acid [CA]) with PL and CEase were studied by inhibition kinetics, multispectroscopy, and molecular docking methods. Enzyme inhibition and inhibition kinetics showed that pentacyclic triterpenoid acids effectively inhibited PL and CEase in a competitive manner with IC50 values ranging from 0.077 mg/mL to 0.446 mg/mL. UV–Vis, fourier transform infrared, fluorescence quenching, and circular dichroism analysis demonstrated that OA, UA, and CA disrupted the conformation of PL and CEase through hydrogen bonding and hydrophobic forces, resulting in loose protein structures. Molecular docking analysis revealed that pentacyclic triterpenoid acids could stably bind at key residues in the active site of PL and CEase. Molecular dynamics (MD) simulation further confirmed the stable binding of pentacyclic triterpene acids to PL and CEase. This study suggested that OA, UA, and CA could have an essential value as digestive enzyme inhibitors.