An Integrated Peptidomics and In Silico Approach to Identify Novel Anti-Diabetic Peptides in Parmigiano-Reggiano Cheese

• Published in: Biology (Basel, Switzerland) Vol. 10; no. 6; p. 563
• Main Authors: Martini, Serena, Solieri, Lisa, Cattivelli, Alice, Pizzamiglio, Valentina, Tagliazucchi, Davide
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 21-06-2021; MDPI
• Subjects: Advanced glycosylation end products; Angiotensin; Antihypertensives; Bioactive compounds; bioactive peptides; Cheese; Dairy products; Diabetes; Diabetes mellitus; Digestive enzymes; Dipeptidyl-peptidase IV; Drug therapy; Enzymatic activity; enzyme inhibition; Enzymes; Food; Glucagon; Glucose; Glycosylation; Hyperglycemia; Insulin; mass spectrometry; Mass spectroscopy; Metabolism; Molecular weight; Parmigiano-Reggiano; Peptidase; Peptides; peptidomics; Peptidyl-dipeptidase A; Proteins; Ripening; Risk factors; type-2-diabetes; α-Amylase; α-Glucosidase; Italy
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology10060563

Inhibition of key metabolic enzymes linked to type-2-diabetes (T2D) by food-derived compounds is a preventive emerging strategy in the management of T2D. Here, the impact of Parmigiano-Reggiano (PR) cheese peptide fractions, at four different ripening times (12, 18, 24, and 30 months), on the enzymatic activity of α-glucosidase, α-amylase, and dipeptidyl peptidase-IV (DPP-IV) as well as on the formation of fluorescent advanced glycation end-products (fAGEs) was assessed. The PR peptide fractions were able to inhibit the selected enzymes and fAGEs formation. The 12-month-ripening PR sample was the most active against the three enzymes and fAGEs. Mass spectrometry analysis enabled the identification of 415 unique peptides, 54.9% of them common to the four PR samples. Forty-nine previously identified bioactive peptides were found, mostly characterized as angiotensin-converting enzyme-inhibitors. The application of an integrated approach that combined peptidomics, in silico analysis, and a structure–activity relationship led to an efficient selection of 6 peptides with potential DPP-IV and α-glucosidase inhibitory activities. Peptide APFPE was identified as a potent novel DPP-IV inhibitor (IC50 = 49.5 ± 0.5 μmol/L). In addition, the well-known anti-hypertensive tripeptide, IPP, was the only one able to inhibit the three digestive enzymes, highlighting its possible new and pivotal role in diabetes management.