An efficient strategy for the rapid exploration of lipase inhibitors derived from the Lindera aggregate leaves by utilizing hybrid lipase-catalytic zeolitic imidazolate framework reactor combined with HPLC-Q-TOF-MS/MS and molecular docking techniques

The leaves of Lindera aggregata (L. aggregata-L), which contain unspecified bioactive components, are a popular tea known for their lipid-regulating properties. This study established a novel and efficient strategy utilizing hybrid lipase–proline metal-organic framework (MOF), combined with HPLC-Q-TOF-MS/MS and molecular docking techniques, to identify potent lipase inhibitors in L. aggregata-L. Porcine pancreatic lipase (PPL) was immobilized within a zeolitic imidazolate framework through biomineralization, and proline was employed to enhance enzyme stability. Consequently, seven lipase inhibitors were initially identified using HPLC-Q-TOF-MS/MS and were subsequently confirmed through nuclear magnetic resonance (NMR) analysis. Their inhibitory activities were validated through an in vitro lipase inhibitory assay. Notably, quercetin-5-O-β-D-glucoside, quercetin-3-O-α-D-xyloside, quercetin-3-O-α-L-arabinofuranoside, and kaempferol-7-O-α-L-rhamnopyranoside were identified as novel lipase inhibitors. The mechanisms of their inhibition were preliminarily investigated through molecular docking and molecular dynamics simulations. This research provided valuable chemical insights into L. aggregata-L for the development of health foods and pharmaceuticals, particularly as a source of natural lipid-regulating drugs.