Computer-Aided Screening and Revealing Action Mechanism of Food-Derived Tripeptides Intervention in Acute Colitis

Abstract

Food-derived tripeptides can relieve colitis symptoms; however, their alleviation mode has not been systematically evaluated as an alternative nutritional compound. This study aimed to reveal the potential mechanism of 8000 food-derived tripeptides against acute colitis using a computer-aided screening strategy. Forty-one potential hub targets related to colitis with a Fit score > 4.0 were screened to construct the protein-protein and protein-tripeptide network based on the PharmMapper database and STRING software (Ver. 11.5). In addition, 30 significant KEGG signaling pathways with p-values < 0.001 that the 41 hub targets mainly participated in were identified using DAVID software (Ver. 6.8), including inflammatory, immunomodulatory, and cell proliferation and differentiation-related signaling pathways, particularly in the Ras- and PI3K-Akt signaling pathways. Furthermore, molecular docking was performed using the Autodock against majorly targeted proteins (AKT1, EGFR, and MMP9) with the selected 52 tripeptides. The interaction model between tripeptides and targets was mainly hydrogen-bonding and hydrophobic interactions, and most of the binding energy of the tripeptide target was less than −7.13 kcal/mol. This work can provide valuable insight for exploring food-derived tripeptide mechanisms and therapeutic indications.