Porcine-derived PR39 antimicrobial peptide alleviates lipopolysaccharide-induced intestinal inflammatory injury in mice by modulating NF-κB/MAPK signaling pathway and intestinal flora.

PR39 is an antimicrobial peptide (AMP) with multiple biological functions, including immune regulation. Lipopolysaccharide (LPS), as the bacterial endotoxin of Gram-negative bacteria, is one of the primary triggers for bacterial infection-induced inflammatory damage in intestinal tissues. However, there are limited reports on whether PR39 has a mitigating or therapeutic effect on LPS-induced acute small intestinal inflammation in mice. This study aimed to investigate the therapeutic effects of PR39 on LPS-induced enteritis in mice and its potential mechanisms of action. The results showed that PR39 alleviated LPS-induced weight loss and organ damage in the liver and kidneys, regulated serum inflammatory factor levels (IL-1β, IL-6, TNF-α, IFN-γ, and IL-10), reduced intestinal leakage markers (DAO, D-LA, and LPS) levels, and enhanced the antioxidant capacity (MDA, CAT, SOD, and T-AOC) of the jejunum in LPS-induced mice. In addition, PR39 up-regulated the number of goblet cells and Muc2 secretion and enhanced the expression of related tight junction proteins. Its mechanism of action may involve inhibiting the phosphorylation levels of proteins associated with the NF-κB/MAPK signaling pathway and regulating the relative abundance of potentially beneficial gut microbiota, including Akkermansia, Phocaeicola, Barnesiella, and butyric acid-producing bacterium Ruminococcus. At the cellular level, PR39 also alleviates LPS-induced inflammatory damage in intestinal epithelial cells by inhibiting the NF-κB/MAPK signaling pathway. In conclusion, PR39 may have potential as a therapeutic drug for treating intestinal inflammatory damage caused by bacterial infections.