Abstract

The egg-derived tripeptides IRW and IQW have been widely reported to possess anti-inflammatory and -antioxidant effects. This study aims to investigate their mechanistic roles in modulating the LPS-induced acute intestinal immune stress. The findings indicated that IRW and IQW significantly alleviated the LPS-induced intestinal and mitochondrial damage. Notably, IRW and IQW significantly reduced the release of mitochondrial N-formyl peptides (mtNFPs) caused by mitochondrial damage, which could activate FPR2. Consistently, FPR2 expression in the intestinal tissue was suppressed following peptide treatment. In addition, IRW and IQW inhibited ERK1/2 phosphorylation, which is potentially linked to improved mitochondrial function and reduced FPR2 expression. Metabolic analysis revealed elevated aspartate and glutamine levels while decreasing l-serine levels, which favored mitochondrial function recovery, suggesting that IRW and IQW can regulate mitochondrial function through amino acid metabolism. Overall, these findings indicate that the alleviating effects of IRW and IQW on LPS-induced intestinal immune stress are associated with the FPR2-mitochondrial axis.