Angelica oil restores the intestinal barrier function by suppressing S100A8/A9 in mice with ulcerative colitis

Background: Ulcerative colitis (UC) progression is driven by the activation of immune cells that release pro -inflammatory mediators to disrupt intestinal epithelial barrier integrity. This study aimed to investigate the potential protective effects of Angelica oil (AO) on the intestinal epithelial barrier in mice with UC and the underlying mechanisms. Methods: Improvement of the disease state and protective effect of AO on the intestinal epithelial barrier were observed in mice with dextran sulphate sodium salt (DSS)-induced UC. Protein microarrays were used to screen AO-affected cytokine pools and their recruited immune cells for accumulation in the tissues. Furthermore, quantitative proteomics was applied to search for AO-acting molecules and to verify in vitro the functions of key molecules between inflammation and the intestinal mucosal barrier. Results: AO significantly alleviated intestinal inflammation, reduced intestinal permeability, and retained barrier function in mice with UC. Furthermore, cytokines inhibited by AO mainly promoted monocyte and neutrophil activation or chemotaxis. Moreover, proteomic screening revealed that S100A8/A9 was a key molecule signif-icantly regulated by AO, and its mediated TLR4/NF-kappa B pathway was also inhibited. Finally, we verified that AO inhibited the activation of the S100A8/A9/TLR4 signalling pathway and enhanced the expression of tight junctions (TJs) proteins using a cellular model of intestinal barrier damage induced by S100A8/A9 or macrophage-derived medium. And the enhancement of TJs in intestinal epithelial cells and the inhibition of inflammatory signalling by AO were significantly attenuated due to the application of S100A8/A9 monoclonal antibody. Conclusion: These results demonstrated that AO improves intestinal mucosal barrier damage in the inflammatory environment of mice with UC by inhibiting the expression of S100A8/A9 and the activation of its downstream TLR4/NF-kappa B signalling pathway.

Automated summary

This study found that Angelica oil has a protective effect on the intestinal mucosal barrier in mice with ulcerative colitis, and it improves barrier damage by inhibiting the expression and activation of S100A8/A9 and the TLR4/NF-kappa B signaling pathway in the inflammatory environment.