Mechanistic Role of Yellowfin Tuna Fish Bone Collagen Peptides in Wound Healing
Wound healing is a highly complex biological process requiring the coordinated regulation of inflammation, fibroblast activation, angiogenesis, and extracellular matrix (ECM) remodelling. Collagen-derived peptides have received increased attention as bioactive agents capable of accelerating tissue repair; however, the specific peptide sequences and their underlying molecular mechanisms remain insufficiently elucidated. This study aimed to characterize collagen and collagen-derived peptides obtained from yellowfin tuna (Thunnus albacares) bone and to investigate their potential mechanistic roles in wound healing using an integrated proteomic and network pharmacology approach. Pepsin-soluble collagen was successfully extracted from tuna bone with a yield of 4.5%. The extracted collagen showed acceptable physicochemical and microbiological characteristics, including low moisture content (0.97%), absence of detectable Salmonella and Coliform contamination under the tested conditions, and a white, odourless appearance. These results suggest effective drying and basic microbiological acceptability of the collagen preparation. Fourier transform infrared analysis showed characteristic amide A, B, I, II, and III absorption bands that closely corresponded to those of standard collagen, provided supportive spectral evidence. Following tryptic digestion during proteomic sample preparation, liquid chromatography–high resolution mass spectrometry (LC-HRMS) analysis identified 15 collagen-derived peptide sequences enriched in glycine–proline motifs and originating from multiple collagen isoforms. Network pharmacology analysis showed 64 overlapping target genes between the identified peptides and wound-healing–related genes. Protein–protein interaction network analysis highlighted several important hub genes, including MMP9, MMP3, MMP2, MMP13, STAT3, PTGS2, and CXCR4, which have important roles in ECM remodelling, inflammatory regulation, cell migration, and angiogenesis. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated significant involvement of major signalling pathways such as IL-17, TNF, NF-κB, and PI3K–Akt, underscoring the multi-target and multi-pathway actions of the peptides. Overall, these results showed that collagen peptides derived from yellowfin tuna bone contribute to wound healing not only as structural ECM components but also as bioactive regulators of important molecular pathways, supporting their potential application as sustainable therapeutic agents and functional biomaterials for wound management. Key words: Marine peptides, biomaterials, pepsin-soluble collagen, hub genes; nutraceuticals