Metabolomic insights into antioxidant properties of blueberry (Vaccinium croymbosum) leaves and a preliminary exploration of their in vitro lipid-lowering activity

In this study, the metabolite differences and antioxidant and in vitro lipid-lowering activities of Vaccinium corymbosum “Lanmei 1” leaves from six different regions in China were evaluated. Integrated untargeted metabolomics and antioxidant assays identified Zhejiang-sourced leaves (ZJ-1) as optimal, demonstrating exceptional phenolic (267.72 mg/g), flavonoid (708.33 mg/g), and proanthocyanidin (422.81 mg/g) contents. Metabolomic profiling detected 1968 compounds, with flavonoid derivatives driving ZJ-1's superior antioxidant capacity. In cellular hyperlipidemia models, ZJ-1 extract exhibited dose-dependent lipid clearance, while pancreatic lipase (PL) inhibition assays revealed an IC 50 of 6.054 mg/mL versus orlistat (0.3518 mg/mL). Molecular docking confirmed stronger binding affinities of ZJ-1's primary constituents—chlorogenic acid (−9.758 kcal/mol) and quercetin (−9.192 kcal/mol)—to PL catalytic residues compared to orlistat (−5.271 kcal/mol). These results establish blueberry leaves as dual-functional antioxidant-hypolipidemic resources, with geographic origin critically modulating phytochemical profiles. This research advances the application of underutilized leaf biomass for nutritional healthcare.