Unlocking the hypolipidemic potential of bioactive peptides derived from probiotic fermented cattle, camel, goat, and sheep milk: a comprehensive investigation through in vitro, in silico, and molecular docking studies

With hyperlipidemia posing a significant cardiovascular risk, innovative strategies are essential to unlock new therapeutic possibilities. Probiotic fermentation of milk proteins offers a natural and effective means to produce peptides with hypolipidemic properties, providing a promising approach to lowering lipid levels and reducing cardiovascular risk. In this study, fermented cattle milk (FCTM), fermented camel milk (FCM), fermented goat milk (FGM), and fermented sheep milk (FSM) were produced using a total of five probiotic bacterial strains to investigate the release of bioactive peptides (BAPs) with hypolipidemic potential via in vitro inhibitory activity toward pancreatic lipase (PL) during a 14-day refrigerated storage study. The PL inhibitory activities of these fermented milk (FM) varied according to the types of probiotic strains and milk types used. Overall, the Pediococcus pentosaceus MF000957 (PP-957) strain showed the highest PL inhibitory activity spanning across all milk types, and therefore, PP-957-derived fermented samples were analyzed for BAP identification by LCMS-QTOF. The identified BAPs were further analyzed using in silico and bioinformatics approaches for bioactivity prediction, molecular docking, and drug pharmacokinetic studies. Overall, four peptides derived from FCTM, one from FCM, and two peptides common in FGM and FSM were predicted as active PL inhibitors based on their binding energy and number of binding sites on the PL enzyme. All peptides were non-toxic, non-carcinogenic, and had appropriate drug-like properties. The outcomes of this study suggest that FM-derived peptides from animal milk are anticipated to be useful for combating hypercholesterolemia.