Exploring the dipeptidyl peptidase-IV inhibitory potential of probiotic-fermented milk: An in vitro and in silico comprehensive investigation into peptides from milk of different farm animals

Bioactive peptides produced via enzymatic hydrolysis have been widely investigated for their dipeptidyl peptidase-IV (DPP-IV) inhibitory properties. However, the deficit of studies on fermentation as a means to produce DPP-IV inhibitory peptides prompted us to draw a comparative study on DPP-IV inhibitory peptides generated from cow, camel, goat, and sheep milk using probiotic fermentation. Further, peptide identification, in silico molecular interactions with DPP-IV, and ensemble docking were performed. Results suggested that goat milk consistently exhibited greater degrees of hydrolysis than other milk types. Further, Pediococcus pentosaceus (PP-957) emerged as a potent probiotic, with significantly lower median inhibitory concentration values of DPP-IV, of 0.17, 0.12, and 0.25 µg/mL protein equivalents in fermented cow, camel, and goat milk, respectively. Overall, peptides (RPPPPVAM, CHNLDELKDTR, and VLSLSQPK) exhibited strong binding affinity, with binding energies of -9.31, -9.18, and -8.9 kcal/mol, respectively, suggesting their potential role as DPP-IV inhibitors. Overall, this study offers valuable information toward antidiabetic benefits of fermented milk products via inhibition of DPP-IV.