Emodin Ameliorates Intestinal Dysfunction by Maintaining Intestinal Barrier Integrity and Modulating the Microbiota in Septic Mice

Sepsis-induced inflammatory response leads to intestinal damage and secondary bacterial translocation, causing systemic infections and eventually death. Emodin is a natural anthraquinone derivative in many plants with promising bioactivities. However, the effects and mechanisms of emodin on sepsis-induced intestinal dysfunctions have not been well clarified yet. We found that emodin treatment suppressed the inflammatory response in the intestines of septic mice. Intestinal barrier function was also improved by emodin through enhancing ZO-1 and occludin expression, which prevented the secondary translocation of Escherichia coli. By proteome microarray investigation, JNK2 was identified as a direct target of emodin. In vitro study also showed that emodin inhibited LPS-induced inflammatory response in intestinal epithelial cells. Nuclear factors including NF-kappa B and AP-1 were further identified as downstream effectors of JNK2. Bioinformatic analysis based on 16s rRNA gene sequencing illustrated that emodin treatment significantly increased the alpha- and beta-diversity of gut microbiota in septic mice. Moreover, data according to functional prediction showed that emodin decreased the abundance of potential pathogenic bacteria in gut. Our findings have shown that emodin treatment prevented inflammatory induced barrier dysfunction and decreased the potential pathogenicity of lumen bacteria, reducing the hazard of lumen bacterial translocation during sepsis.