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Profiling alterations of the metabolomic and transcriptomic characteristics and the therapeutic mechanism of Psoraleae Fructus in treating kidney-yang deficiency syndrome rats

ABSTRACT: Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by neuroendocrine disorders often accompanied by abnormal liver function. Psoraleae Fructus (BGZ) is widely used to treat KYDS in China, but it is unclear whether BGZ plays a therapeutic role in regulating liver function. Organ index, ALT, AST, and HE staining were used to evaluate the protective effect of BGZ on KYDS in rats, and transcriptomics and metabolomics were employed to screen for potential biomarkers. The results showed that BGZ treatment significantly decreased the levels of ALT and AST, and ameliorated liver pathological damage in KYDS rats. 92 differentially expressed genes (DEGs) and 20 metabolites were significantly disturbed by BGZ in KYDS rats. Integrated analysis of metabolites and DEGs revealed that neuroactive ligand-receptor interaction, cAMP pathway, calcium signaling pathway, and cytokine-cytokine receptor interaction may be the main mechanism of BGZ treatment, and the key targets of the cAMP pathway were confirmed by ELISA and RT-qPCR. In conclusion, the cAMP pathway may be the partial mechanism by which BGZ exerts protective effects on KYDS, and the study results also lay the foundation for more in-depth mechanistic studies and drug-targeted therapy of KYDS in the future.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE249348 | GEO | 2023/12/31

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 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.

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Profiling alterations of the metabolomic and transcriptomic characteristics and the therapeutic mechanism of Psoraleae Fructus in treating kidney-yang deficiency syndrome rats

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