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


CONCLUSIONS
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.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
Jun
J
Liu
Cai-Xiu
CX
Zhou
Zhan-Jun
ZJ
Zhang
Li-Ying
LY
Wang
Zhi-Wei
ZW
Jing
Zhong
Z
Wang
D000818:Animals; D016000:Cluster Analysis; D004396:Coloring Agents; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D030541:Databases, Genetic; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D039823:Iridoids / Q000627:therapeutic use*; D051379:Mice; D046228:Microarray Analysis; D025341:Principal Component Analysis; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D020521:Stroke / Q000188:drug therapy / Q000209:etiology; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D004396:Coloring Agents; D018076:DNA, Complementary; D039823:Iridoids; C007835:geniposide; D012313:RNA; D014580:Ursodeoxycholic Acid