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

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.

Potential targets and the action mechanism of food-derived dipeptides on colitis: network pharmacology and bioinformatics analysis.

Food-derived peptides can ameliorate colitis but their pharmaceutical targets and action mechanism of ameliorating colitis remain unclear. Here, we aim to investigate the action mechanism of food-derived peptides ameliorating colitis based on the network pharmacology and bioinformatics analysis. 400 dipeptides were used to screen the core targets based on the PharmMapper and GeneCards database. A total of 49 core targets were screened to construct the predicted target set. The target set was then evaluated using the STRING software to construct the protein-protein and protein-dipeptide network. Furthermore, the DAVID software was used to analyze the GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of the core targets. The results of bioinformatics assays showed that the 49 targets mainly participated in the inflammatory and immunomodulatory signaling pathways, particularly in the inflammatory bowel disease-related signaling pathways IL-6/JAK2/STAT3 and TLR4-NF-κB/MAPK. In addition, molecular docking results confirmed that 25 dipeptides mainly interacted with the core targets (ALB, JAK2, and STAT3) by hydrogen-bonding interactions. This study can provide evidence for the potential efficacy and action pathways of food-derived peptides on colitis.