Effect of the Pseudopleuronectes americanus-derived Pleurocidin on DSS-induced Ulcerative colitis in mice and its preliminary molecular mechanisms

Pleurocidin is an antimicrobial peptide derived from the mucous membranes of the skin or intestinal secretions of Pseudopleuronectes americanus that has antimicrobial and immunomodulatory activities. Ulcerative colitis is recognized as a widespread human disease that may be influenced by environmental and genetic factors. Evidence emphasizes the critical role of the gut microbiota in UC. Synthetic Pleurocidin was analyzed by a combination of liquid chromatography and mass spectrometry. Pleurocidin pharmacological effects were evaluated by DAI score, colon histological score, cytokine levels, and tight junction protein expression in mice. The preliminary molecular mechanism was explored by the levels of key proteins in the NF-κB and MAPK inflammatory signaling pathways in colon tissues. The main analytical methods such as immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blot were used. We then used 16S rRNA gene sequences to characterize the gut microbiota. Firstly, our study demonstrated that rectal injection of Pleurocidin at 5 mg/kg body weight alleviated clinical symptoms and colonic histopathological changes in UC mice caused by DSS. Secondly, Pleurocidin altered the abnormal levels of inflammatory and immune-related cytokines in serum, modulated the significant down-regulation of tight junction proteins, and inhibited the expression of NF-κB and MAPK inflammatory signaling pathway-related proteins. Finally, Pleurocidin can regulate gut microbiota, increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. In conclusion, Pleurocidin alleviates UC symptoms in mice, and its effects on the gut microbiome may be potential pathways. It is providing a promising therapeutic option for UC.