Exploration of the Mechanism of Guaijaverin in Inhibiting Pancreatic Lipase Based on Multispectral Method, Molecular Docking, and Oral Lipid Tolerance Test in Rats

ABSTRACT This study aims to investigate the action mechanism of guaijaverin on pancreatic lipase from multiple perspectives and provide a theoretical basis for the search for new pancreatic lipase inhibitors. The inhibition of pancreatic lipase by guaijaverin was investigated through enzyme inhibition activity experiments, and the IC 50 was calculated to determine the type of inhibition of guaijaverin. The mechanism of action was studied by measuring fluorescence, ultraviolet spectra, and circular dichroism. Molecular docking technology was used to explore the binding situation. In addition, in vivo oral lipid tolerance tests in rats were carried out to investigate the inhibitory effect of guaijaverin on pancreatic lipase. Guaijaverin inhibited pancreatic lipase up to 90.63%, confirming its excellent inhibitory ability. The inhibition type was noncompetitive inhibition in reversible inhibition. The multispectral experiments indicated that its quenching type was static quenching and guaijaverin changed the microenvironment and spatial conformation of pancreatic lipase. The molecular docking results showed that the minimum binding energy between the two compounds was −6.96 kcal/mol. In vivo experiments demonstrated that guaijaverin inhibits pancreatic lipase by reducing TG uptake in the body. Guaijaverin has excellent inhibitory effects on pancreatic lipase and has the potential to function as a pancreatic lipase inhibitor.