Yu_2025_J.Sci.Food.Agric__

BACKGROUND: Naringin, a natural flavonoid compound, has demonstrated potential anti-obesity effects by modulating lipid metabolism. Pancreatic lipase plays a critical role in lipid digestion and absorption, making it a key target for obesity management. This study investigated the inhibitory mechanism of naringin on pancreatic lipase through in vitro, in vivo, and in silico experiments. RESULTS: In vitro experiments revealed that naringin was a competitive inhibitor of pancreatic lipase, with a half-maximal inhibitory concentration (IC50) of 6.93 +/- 0.12 mmol/L. Multi-fluorescence spectroscopy confirmed that naringin induced secondary structure changes and static fluorescence quenching of pancreatic lipase, with a binding constant of 2.16 x 10(4) L/mol. Isothermal titration calorimetry indicated a spontaneous exothermic reaction (-26.08 kJ/mol), mainly driven by hydrogen bonding and electrostatic force. In vivo studies demonstrated that naringin decreased serum lipase activity by 24.54%, mitigated hepatic lipid accumulation, and down-regulated inflammatory cytokines in high-fat diet-induced obese rats. Molecular simulation further revealed that hydrogen bonding was the primary interaction force between naringin and pancreatic lipase. CONCLUSIONS: Naringin effectively inhibits pancreatic lipase through competitive binding and structural modifications, reducing lipid digestion and absorption. The inhibitory effect of naringin on pancreatic lipase might provide new insights into the role of naringin in lipid metabolism regulation and potential application in obesity management. 2025 Society of Chemical Industry.