Camel Milk Lactoferrin DPP-IV Inhibitory Peptide: Screening, Validation, and Potential Mechanisms in Diabetes Prevention and Treatment (2023)

Experimental Methods: 

Three different types of proteases were selected for in silico enzymatic hydrolysis of the camel milk lactoferrin (LF) sequence. The study involved screening for DPP-IV inhibitory peptides, Peptide Ranker scoring, molecular docking screening, artificial synthesis of target peptides, DPP-IV inhibition rate assays, analysis of peptide inhibition patterns, molecular docking to investigate the binding sites and interaction modes between peptides and DPP-IV, and prediction of potential anti-diabetic targets of the peptides. The identified anti-diabetic targets of the selected peptides were imported into the DAVID platform, with the species restricted to Homo sapiens (P < 0.05). The enrichment results were saved and visualized using the Microbiotechnology platform.

Results: 

The study found that GPQY acts on core targets such as STAT3, MMP9, SRC, and MAPK1. It participates in the IL-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, and apoptotic metabolic pathways to inhibit the secretion of inflammatory factors, exert anti-inflammatory effects, inhibit β-cell apoptosis, and improve insulin resistance, thereby playing a role in combating diabetes. Additionally, GPQY was found to regulate neuroactive ligand-receptor interactions, the renin-angiotensin system, the relaxin signaling pathway, pathways in cancer, and lipid and atherosclerosis-related signaling pathways. These mechanisms contribute synergistically to the prevention and treatment of diabetic complications, including cardiovascular disease, neuropathy, diabetic nephropathy, retinopathy, and cancer.

Conclusion: 

Camel milk LF is a promising source of DPP-IV inhibitory peptides. The tetrapeptide GPQY derived from it may prevent and manage diabetes and its complications through multi-target and multi-pathway mechanisms, including involvement in inflammatory responses and regulation of cell proliferation and differentiation.

Table 1: Interaction forces of the optimal docking conformation between the peptide and DPP-IV

Table 2: KEGG enrichment analysis (A) and GO enrichment analysis (B) of 82 diabetes-related targets of GPQY

Institution: College of Food Science and Engineering, Northwest A&F University & Yibate Camel Milk Product Research and Development Center

Source: Xie Yuxia, Ge Wupeng, Bai Hang, Li Guowei, et al. Screening and validation of DPP-IV inhibitory peptides from camel milk lactoferrin and their potential mechanisms in diabetes prevention and treatment [J]. Science and Technology of Food Industry, 2023, 44(6): 384–395.