Genipin inhibits lipopolysaccharide-induced acute systemic inflammation in mice as evidenced by nuclear factor-κB bioluminescent imaging-guided transcriptomic analysis

Genipin is a natural blue colorant in food industry. Inflammation is correlated with human disorders, and nuclear factor-κB (NF-κB) is the critical molecule involved in inflammation. In this study, the anti-inflammatory effect of genipin on the lipopolysaccharide (LPS)-induced acute systemic inflammation in mice was evaluated by NF-κB bioluminescence-guided transcriptomic analysis. Transgenic mice carrying the NF-κB-driven luciferase genes were administered intraperitoneally with LPS and various amounts of genipin. Bioluminescent imaging showed that genipin significantly suppressed LPS-induced NF-κB-dependent luminescence in vivo. The suppression of LPS-induced acute inflammation by genipin was further evidenced by the reductions of cytokine levels in sera and organs. Microarray analysis of these organs showed that the transcripts of 79 genes were differentially expressed in both LPS and LPS/genipin groups, and one third of these genes belonged to chemokine ligand, chemokine receptor, and interferon (IFN)-induced protein genes. Moreover, network analysis showed that NF-κB played a critical role in the regulation of genipin-affected gene expression. In conclusion, we newly identified that genipin exhibited anti-inflammatory effects in a model of LPS-induced acute systemic inflammation via downregulation of chemokine ligand, chemokine receptor, and IFN-induced protein productions.

Graphical abstractDownload full-size imageHighlights► Genipin suppressed LPS-induced acute systemic inflammation. ► Genipin altered the expression of chemokine ligand and chemokine receptor genes. ► Genipin downregulated the expression of IFN-induced protein genes. ► NF-κB was a central molecule in regulation of genipin-altered gene expression.