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

• Published in: International immunopharmacology Vol. 130; p. 111757
• Main Authors: Nong, Keyi, Liu, Zhineng, Qin, Xinyun, Chen, Wanyan, Zhang, Bin, Wu, Yijia, Wang, Zihan, Fang, Xin, Liu, Youming, Wang, Xuemei, Shi, Huiyu, Zhang, Haiwen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.03.2024
• Subjects: Animals; Antimicrobial peptides; Colitis; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Fish Proteins; Flounder; Humans; Intestinal barrier; Intestinal flora; Mice; Mice, Inbred C57BL; NF-kappa B; Pseudopleuronectes americanus; RNA, Ribosomal, 16S; Pseudopleuronectes americanus; Intestinal barrier; Colitis; Intestinal flora; Antimicrobial peptides
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111757

In this study, we investigated the effect of Pleurocidin on ulcerative colitis in mice. The results showed that Pleurocidin ameliorated DSS-induced colon shortening, colon tissue damage, and disruption of tight junctions. Secondly, it alleviated macrophage and neutrophil infiltration, down-regulated the concentration of pro-inflammatory cytokines and up-regulated the concentration of anti-inflammatory cytokines, and inhibited the expression of NF-κB and MAPK inflammatory signaling pathway proteins. Finally, 16S rRNA sequencing demonstrated that Pleurocidin improved the flora structure, decreased the abundance of harmful bacteria and increased the abundance of beneficial bacteria. This study suggests that Pleurocidin has potential in the treatment of IBD, and provides a reference for the subsequent identification of Pleurocidin therapeutic targets in the treatment of IBD, and lays the foundation for further research on the biological functions of Pleurocidin. [Display omitted] •Pleurocidin recoveres intestinal damage in UC mice.•Pleurocidin regulates the structure of intestinal flora.•Pleurocidin regulates NF-κB and MAPK pathways. 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.