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Ellagic acid activated PPAR signaling pathway to protect ileums against castor oil-induced diarrhea in mice: Application of transcriptome analysis in drug screening

ABSTRACT: Background: Acute diarrhea is still a common and serious disease. The causes of acute diarrhea are very complicated. Therefore, we need to find a medicine to control diarrhea symptoms, save time for diagnosis of pathogens, and prevent drug abuse. Ellagic acid (EA), a natural polyphenol drug, has anti-diarrhea effects. However, the action mechanisms of EA for non-specific diarrhea have not been characterized. Materials and methods: To study the mechanisms of EA, mice were divided into four groups (group C were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml physiological saline, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group D were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group E were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Group V were intraperitoneally injected with 0.1ml GW9662 (1m g/ml) and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml).) Transcriptome were performed on ileum tissues of mice in group D and E. Histological examination and qRT-PCR were performed on ileum tissues of mice in group C, D, E and V. Results: We found that a total of 273 differentially expressed genes (DEGs) were obtained, including 160 up-regulated DEGs and 113 down-regulated DEGs. The DEGs were enriched in 458 Gene Ontology (GO) terms and 15 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. The peroxisome proliferator activated receptor (PPAR) signaling pathway was the most significantly enriched in KEGG pathways. We used the PPAR-specific antagonist GW9662 to validate the anti-diarrhea and anti-inflammatory effect of EA in group V compared with group E. Conclusively, EA protected ileums against castor oil-induced inflammation and diarrhea by activating the PPAR signaling pathway and a method was used to study the mechanism of EA.

ORGANISM(S): Mus musculus

PROVIDER: GSE142063 | GEO | 2020/02/24

REPOSITORIES: GEO

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Project description:Aim: To find the genes that related with the drug's(7-P) function. Design: 36 Rats were randomly divided into three group:control group(12), model group(12) and drug group(12). At last, randomly choosing 3 Rat from each group to do genechip analysis. In model group, the Porcine serum was given intraperitoneally (i.p.) to rats in a volume of 1.5 mL/kg every 3 days for a total of 20 treatments. Effect on model animals was confirmed by liver histology and biochemical assays . In drug group, 7-P was dissolved in balanced saline solution for administration subcutaneously at dosages of 174 μg/kg in a volume of 1 mL/kg. The doses were given 15 times, one day interval. In control group, the animals were not treated with porcine serum. but given an equal volume of vehicle alone. During 7-P and vehicle administration, porcine serum was given intraperitoneally (i.p.) to rats in a volume of 1.5 mL/ kg once weekly. All animals were fasted for 24 h before porcine serum treatment. Background: During investigation of hypervariable region 1 (HVR1) of hepatitis C virus (HCV), a seven amino acids mimic peptide named 7-P was identified within the N-terminal of HVR1 that could induce IFN-γ and IL-10 expression while decreasing the expression of TNF-α in vivo and in vitro. Further studies revealed that 7-P could not only decrease the serum levels of aminotransferases (ALT, AST), alkaline phosphatase (AKP), and billirubin, but were also effective in reversing histopathological evidence of inflammation-mediated hepatic injury in 3 rat models. The protective mechanism and gene expression profiles were investigated in detail in a rat chronic liver injury model using Affymetrix microarrays . Conclusion: We found that IL-1β, tumor necrosis factor receptor superfamily 14 (TNFRSF14), intercellular adhesion molecule 2 (ICAM2), sterol regulatory element-binding protein 1 (SREBP 1), Prohibitin (PHB), and inhibitor of DNA binding 2 (Id2) were the target genes that related with 7-P Keywords: comparative genomic hybridization

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Ellagic acid activated PPAR signaling pathway to protect ileums against castor oil-induced diarrhea in mice: Application of transcriptome analysis in drug screening

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