Virtual screening and multi-synergism of inhibitory compounds against pancreatic lipase

In response to the adverse effects associated with chemically synthesized pancreatic lipase (PL) inhibitors and the limited efficacy of individual natural functional compounds, this investigation aims at virtually screening potential PL inhibitors from natural plant-sourced materials and evaluating their multi-synergism through molecular docking, SynergyFinder tool and spectroscopic methods. Luteolin (LUT), quercetin (QUE), and apigenin (API) have been virtually screened out as outstanding PL inhibitors with the IC50 values being 109.7, 190.0 and 276.9 μg/mL. Synergistic score analysis of the PL inhibition rates by SynergyFinder Plus showed that the tri-component synergistic scores were more significant than one- and two-component synergy scores and the inhibition rate could reach 96.8% with LUT: QUE: API of 2 : 3: 12. The inhibitory mechanism of the complex (L-Q-A) on PL is mixed inhibition. L-Q-A exhibits a more potent quenching effect on PL and exerts a more pronounced influence on the secondary structure of PL. The simultaneous muti-ligand molecule docking results further demonstrate the existence of multiple binding pockets of L-Q-A on the PL that can form more hydrogen bonding, hydrophobic interactions and π-π interactions. In conclusion, LUT, QUE, and API exhibit synergistic effects in inhibiting PL activity, holding promise as innovative dietary supplements for mitigating obesity-related symptoms.