Identification of an Antarctic krill (Euphausia superba) peptide with immunoregulatory activity

Antarctic krill is a rich source of bioactive peptides with potential immunomodulatory properties. In this study, in vitro and in vivo models were used to evaluate the immunoregulatory effects of Antarctic krill enzymatic hydrolysates. Among the hydrolysates produced using different enzymes, the neutral protease yielded the highest degree of hydrolysis and most effectively promoted the proliferation of RAW264.7 macrophages. The hydrolysate was further fractionated by ultrafiltration and Sephadex G-15 chromatography, resulting in the isolation of a highly active fraction, NAKP-A, which significantly enhanced macrophage proliferation, phagocytosis, and nitric oxide secretion. HPLC-MS/MS analysis and database screening further identified a key bioactive peptide (RDWPEGRG) exhibiting optimal immunostimulatory activity. Mechanistic studies revealed that RDWPEGRG upregulated the expression of immune-related genes (IL-6, CCL2, and CCL5) and enhanced mitochondrial respiration (as evidenced by an increased oxygen consumption rate) in RAW264.7 cells. Finally, using a rapamycin-induced immunosuppressed zebrafish model, RDWPEGRG was found to effectively restore immune competence by increasing macrophage activity and normalizing neutrophil counts. Collectively, these findings identify RDWPEGRG sourced from Antarctic krill hydrolysates as a potent immunostimulatory peptide, highlighting its potential as a functional ingredient for immune-enhancing food and nutraceutical applications.