Abstract:To rapidly identify safe and effective natural inhibitor of pancreatic lipase (PL), the author utilized molecular docking, spectrophotometry, the orthogonal t-value method, and fluorescence quenching experiments to investigate the interaction between PL and the inhibitors by analyzing PL's conformation, activity, kinetics, and thermodynamics. Results showed that of the 31 screened compounds, 28 exhibited more than 50% inhibition of PL activity, with 11 compounds demonstrating half-maximal inhibitory concentrations (IC50) below 100 μg/mL. Notably, (-)-epigallocatechin gallate (EGCG) and coenzyme Q9 (CoQ9) displayed IC50 values lower than that of orlistat. The author designed compound formula, comprising luteolin, myricetin, quercetin, isoquercetin, and naringin, achieved an inhibition rate of (98.79±2.46)% at a concentration of 0.5 mg/mL and a volume ratio of 15∶6∶17∶5, surpassing the efficacy of individual components. The five substances in the formulation spontaneously bind to PL, leading to the quenching of its intrinsic fluorescence through static quenching. Non-covalent interactions, including hydrophobic interactions, hydrogen bonds, ionic bonds, and π-π stacking, are observed between these substances and PL. This study provides multiple promising candidates for PL inhibitors.
