Investigating the effects of probiotic fermentation on the pancreatic lipase inhibitory activity of sea buckthorn polyphenol extracts by using untargeted metabolomics and multispectral analysis.

In this study, sea buckthorn juice phenolics, free, bound, and conjugated fractions, were investigated for pancreatic lipase (PL) inhibition, and conjugated phenolics (CPs) were found to exhibit the highest inhibitory activity (IC50: 253.9 μg/mL pre-fermentation, 185.2 μg/mL post-fermentation). Fermentation modified the conjugated phenolic composition, upregulating 31 compounds and downregulating 18 compounds, notably protocatechuic acid and isorhamnetin derivatives. Importantly, kinetic analysis demonstrated a fermentation-induced shift in the inhibition mode from mixed-type (unfermented CPs [CCP]) to uncompetitive (fermented CPs [FCP]), suggesting its potential application as an adjunctive therapy. Spectroscopic studies indicated that CP-PL interactions occurred through static quenching and hydrophobic forces, with FCP inducing secondary structural perturbations in PL. Notably, FCP demonstrated synergistic effects with orlistat, suggesting its potential for combined therapeutic applications. These results highlight the value of sea buckthorn as a source of anti-obesity polyphenols and provide a mechanistic basis for the development of functional ingredients that target PL activity regulation. These findings suggest that fermented sea buckthorn phenolics are promising candidates for metabolic disorder interventions owing to their dual inhibition mechanism and structural modulation of PL.