Novel pancreatic lipase inhibitory peptides derived from lotus seed protein: isolation, identification, and the interaction mechanism

In this study, pancreatic lipase (PL) inhibitory peptides were identified from a lotus seed protein (LSP) hydrolysate and the potential mechanism was investigated. The LSP hydrolysate was isolated and purified, and six PL inhibitory peptides were screened; in particular, Phe-Leu-Leu (FLL) and Glu-Phe-Phe (EFF) exhibited the strongest inhibitory activity. Molecular docking results indicated that FLL and EFF interacted with residues around the PL active site through hydrogen bonding and hydrophobic interactions. The Lineweaver-Burk curve revealed that FLL acted as a mixed-type inhibitor, while EFF exhibited non-competitive inhibition of PL. Additionally, fluorescence spectroscopy, circular dichroism (CD), and ultraviolet-visible (UV-Vis) spectrometry analyses confirmed that FLL and EFF altered the microenvironment and secondary structure of PL by increasing the beta-sheet content and reducing the alpha-helix content, thereby decreasing the catalytic activity of PL. Molecular dynamics simulation further confirmed that PL-peptide complexes exhibited a more stable state and compact structure. In summary, FLL and EFF could be used in the development of food supplements for obesity prevention.