Geniposide Achieved an Anti-Inflammatory Effect Through the NF-κB/HIF-1α Signaling Pathway Mediated by VEGFA and HMOX1 Genes

Abstract

Geniposide is a kind of iridoid glycoside compound mainly extracted from the dried and mature fruit of a Rubiaceae plant, Gardenia jasminoides J.Ellis, which has a certain anti-inflammatory effect, but mechanism of this effect remains unclear.In this study, we utilized the network pharmacology approach, molecular docking, and in vitro experiments on the pharmacodynamics and anti-inflammatory mechanism of Geniposide. We leveraged the public databases to uncover putative targets across Geniposide and inflammatory diseases and constructed the anti-inflammatory protein–protein interaction (PPI) network of Geniposide following the intersection targets between them, further molecular docking, and enrichment analysis were performed. Finally, in vitro experiments were conducted to validate the predicted target genes and pathways. A total of 59 Geniposide-related targets and 8954 inflammatory diseases related targets were screened out, and 50 intersection targets were eventually obtained. We took the key target of the top 10 for molecular docking, and vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2, recombination human heme oxygenase 1 (HMOX1), adenosine receptor A1, adenosine deaminasegenes were identified based on the free binding energy. Hypoxia-inducible factor 1 (HIF-1) was predicted as the critical path of Geniposide anti-inflammatory by the Kyoto Encyclopedia of Genes and Genomessignaling pathway enrichment analysis. The results showed that Geniposide could regulate the gene expression of VEGFA and HMOX1 and influence the protein expression levels of HIF-1α, VEGFA,HOMX1,and p-p65 in the NF-κB/HIF-1α signaling pathway. Our data revealed that the anti-inflammatory effect of Geniposide was at least through the NF-κB/HIF-1α signaling pathway mediated by VEGFA and HMOX1 genes.