This study investigated the inhibitory effect and mechanism of 12 LAB strains isolated from Chinese fermented foods on dipeptidyl peptidase-4 (DPP-4) using the Caco-2 cell model. The results showed that the inhibitory effect of cell-free extracts (CFEs) collected from each LAB strain on DPP-4 was higher than that of the cell-free excretory supernatants. The CFEs from Lactobacillus plantarum YE4 (YE4-CFE) exhibited the strongest DPP-4 inhibitory activity (24.33% inhibition). Furthermore, YE4-CFE altered the TNF and MAPK signaling pathways. Additionally, the YE4-CFE ultrafiltration fraction (<3 kDa) displayed a similar DPP-4 inhibitory activity to YE4-CFE. UHPLC-MS/MS identified 19 compounds with a relative proportion of more than 1% in the <3 kDa fraction, and adenine, acetylcholine, and L-phenylalanine were the top three substances in terms of proportion. Altogether, the inhibitory effect of YE4-CFE on DPP-4 was associated with the TNF and MAPK signaling pathways, and with the high proportion of adenine, acetylcholine, and L-phenylalanine.

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