Synergistic mechanism of gene expression and pathways between jasminoidin and ursodeoxycholic acid in treating focal cerebral ischemia-reperfusion injury

摘要

Aim: Jasminoidin and ursodeoxycholic acid are 2 bioactive compounds extracted from Chinese medicine that have been proven to exert a synergistic effect as a combined administration for the treatment of stroke. The aim of this study was to reveal the pharmacogenomic mechanism of this synergistic effect of jasminoidin and ursodeoxycholic acid. Methods: One hundred and fifteen mice with brain damage, induced by focal cerebral ischemia/reperfusion, were divided into 5 groups: jasminoidin-treated, ursodeoxycholic acid-treated, combination-treated, vehicle group, and sham-operated group. Comparative analysis of stroke-related gene expression profiles and Kyoto Encyclopedia of Genes and Genomes pathways among the 3 treatment groups were performed to reveal the mechanism of this synergistic effect. Results: This study demonstrated that (1) treatment with jasminoidin alone caused similar changes in the pattern of gene expression as those treated with the combination; (2) jasminoidin treatment and the combination treatment had more overlapping changes in gene expression and activated pathways than the ursodeoxycholic acid treatment; (3) Hspa1a and Ppm1e were only up-regulated in the combination-treated group; (4) the nonoverlapping genes Fgf12, Rarα, Map3k4, paxillin (PXN) in the combination-treated group were markedly expressed, and P53 pathway was obviously activated in the combination-treated group. Conclusion: These findings may suggest that jasminoidin is the major component of the combination, and the combination plays an important role of the synergistic effect in up-regulating expression of gene Hspa1a, genes Fgf12, Rarα, Map3k4 and down-regulating gene PXN, as well as activating P53 pathway.