Gastrointestinal digestion enhances the release of bioactive peptides from yogurt.

PURPOSE: This study investigated whether simulated gastrointestinal (SGI) digestion enhances the release of bioactive peptides from yogurt and improves their associated bioactivities. METHODS: Yogurt was subjected to INFOGEST-based SGI digestion. Bioactivities were evaluated using ACE and DPP-IV inhibition and DPPH radical scavenging assays. Protein degradation was assessed by SDS-PAGE, and peptides were identified by UPLC-LTQ Orbitrap mass spectrometry, followed by in silico peptide screening and molecular docking. RESULTS: Compared with undigested yogurt, SGI digestion markedly enhanced ACE inhibitory, DPP-IV inhibitory, and antioxidant activities, with IC50: 9.6 µg/mL, 300.3 µg/mL, and 530.7 µg/mL, respectively. SDS-PAGE confirmed extensive protein hydrolysis, accompanied by increased peptide content. Peptidomic analysis identified 129 oligopeptides, predominantly < 1.5 kDa, with 31 prioritized as predicted bioactive candidates. Selected peptides exhibited favorable predicted interactions with ACE, DPP-IV, Keap1, and DPPH. CONCLUSION: SGI digestion promotes the release of low-molecular-weight peptides with enhanced in vitro bioactivities, providing a peptide-level framework for prioritizing yogurt-derived peptide candidates for future validation. Further experimental validation is needed before functional food, nutraceutical, or therapeutic applications can be proposed.