Regulation of ROS-NF-κB axis by tuna backbone derived peptide ameliorates inflammation in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal disease encountered in the premature infant. It has been shown that the intercellular reactive oxygen species (ROS) generation activated by lipopolysaccharide involved in the nuclear factor kappa B (NF-κB) activation and pathogenesis of NEC. Here, we report that an antioxidant peptide from tuna backbone protein (APTBP) reduces the inflammatory cytokines transcription and release. APTBP directly scavenges the free radical through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) assay. In addition, APTBP reduces the intracellular ROS level, exhibiting an antioxidant activity within cells. Remarkably, gavage with APTBP attenuates the phenotype of NEC in the mice model. Mechanically, the NF-κB activation, together with the expression of inflammatory cytokines are decreased significantly when intracellular ROS are eliminated by APTBP. Therefore, our findings demonstrated that an antioxidant peptide, APTBP, ameliorates inflammation in NEC through attenuating ROS-NF-κB axis.

Peptidomics Analysis Discloses That Novel Bioactive Peptides Participate in Necrotizing Enterocolitis in a Rat Model.

Necrotizing enterocolitis (NEC) is a common devastating gastrointestinal disease in premature infants, the molecular mechanisms of which have not been fully elucidated. Recently, endogenous peptides have garnered much attention owing to their role in diagnosis and treatment. However, changes in the peptide expression of NEC intestinal tissues remain poorly understood. In the present study, a comparative peptidomics profiling analysis was performed between NEC and control intestinal tissues via liquid chromatography-tandem mass spectrometry (LC-MS). In total, 103 upregulated and 73 downregulated peptides were identified in the intestinal tissues (fold change ≥ 1.5, p < 0.05). Bioinformatics analysis revealed that these differentially expressed peptides were significantly associated with NEC pathophysiology, including apoptosis, the TGF-ß signaling pathway, the Wnt signaling pathway, and the MAPK signaling pathway. Furthermore, two putative peptides could inhibit apoptosis and promote the migration of intestinal epithelial cells induced by lipopolysaccharide; these peptides were derived from the protein domains MT1 and EZRI, respectively. In conclusion, our study revealed that endogenous peptides are involved in the pathophysiologic mechanism of NEC; nevertheless, further exploration is required in this regard.