Xanthohumol ameliorates dextran sodium sulfate-induced colitis in mice by inhibiting of NF-κB signaling pathways and modulating intestinal microbiota

Ethnopharmacological relevance

Xanthohumol (XN), an isoprenylated flavonoid natural product found only in hops, possesses a variety of biological activities such as anticancer, anti-inflammatory, hepatoprotective, and anti-obesity.

Aim of the study

The aim of this study was to investigate the effects and mechanisms of XN on the treatment of colitis.

Materials and methods

First, acute colitis was induced by using distilled water containing 3% DSS for 10 consecutive days. The therapeutic efficacy of XN was assessed by an established DSS-induced mouse colitis model. Subsequently, disease activity index (DAI) and colon length of mice were assessed. The health of the intestines was assessed by histopathological analysis. Inflammatory factors, IL-1β, IL-6, and TNF-α, were detected in colon tissues by ELISA.Finally, mouse intestinal contents were extracted and subjected to 16 S rRNA Sequencing, and the gut microbiota was analysed for Alpha-diversity and Beta-diversity.

Results

The results showed that XN ameliorated DSS-induced colitis. Furthermore, XN reduced pro-inflammatory cytokine levels such as IL-1β, IL-6, and TNF-α, as well as inhibited the activation of the TLR4/NF-κB pathway, all of which helped to mitigate the inflammatory response. Finally, we also found that XN alleviated intestinal dysbiosis in colitis mice.

Conclusion

In conclusion, our study demonstrated that XN provides protective effects against colitis, and has the potential to be further explored as a lead compound for the treatment of inflammatory bowel disease (IBD).

Graphical Abstract