Marker genes of geniposide-induced hepatotoxicity based on genomic strategy.
10.19540/j.cnki.cjcmm.20190710.401
- Author:
Yan-Zhen HU
1
;
De-Feng LI
2
;
Yi ZHANG
2
;
Jun-Ying WEI
2
;
Hong-Jun YANG
2
Author Information
1. Jiangxi Provincial Institute of Traditional Chinese Medicine Nanchang 330046,China.
2. Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences Beijing 100700,China.
- Publication Type:Journal Article
- Keywords:
Real-time quantitative PCR;
gene chip;
geniposide;
hepatotoxicity
- MeSH:
Animals;
Biomarkers/metabolism*;
Chemical and Drug Induced Liver Injury;
Genomics;
Iridoids/toxicity*;
Liver/metabolism*;
Rats;
Rats, Sprague-Dawley
- From:
China Journal of Chinese Materia Medica
2019;44(19):4234-4240
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this paper was to screen out relevant genes of geniposide-induced hepatotoxicity based on genomics,in order to provide a scientific basis for the non-clinical evaluation of drugs containing Gardeniae Fructus and geniposide. Fifty-five SD rats were randomly divided into normal control group,24 h group and 72 h group. The changes of appearance,behavior and weight of rats were observed after administration by gavage for 3 days. The activities of ALT and AST were detected. Molecular mechanism of geniposideinduced hepatotoxicity was investigated by Affymetrix miRNA 4. 0 and Affymetrix Rat Gene 2. 0 to examine the gene expression levels in Sprague-Dawley rat livers at 24 h and 72 h after administration of overdose-geniposide( 300 mg·kg-1 daily),and then verified by Realtime quantitative PCR. Compared with the normal control group,the activities of ALT and AST were markedly increased. In addition,experimental results indicated that 324 genes were differentially expressed,among which 259 were up-regulated and 65 down-regulated.Nine candidate genes were verified by qRT-PCR,including Bcl2,Il1 b,Tpm3,MMP2,Col1α1,Ifit1,Aldob,Nr0 b2,Cyp2 c23. And Bcl2,Col1α1,Aldob,Nr0 b2 and Cyp2 c23 were found to be correlated with geniposide-induced hepatotoxicity. This study provides an important clue for mechanism of geniposide-induced hepatotoxicity.