6-Shogaol Mitigates Sepsis-Associated Hepatic Injury through Transcriptional Regulation

Nutrients. 2021 Sep 28;13(10):3427. doi: 10.3390/nu13103427.

Abstract

Sepsis-associated liver dysfunction presents a significant public health problem. 6-Shogaol is the key bioactive component in dry ginger, which has antioxidant and anti-inflammation capacity. The present study aims to investigate the preventive effect of 6-shogaol on sepsis-induced liver injury. 6-Shogaol was administered to mice for 7 consecutive days before being intraperitoneally injected with lipopolysaccharide (LPS). After 24 h, mice were sacrificed, and biochemical and transcriptomic analyses were performed. Our results demonstrated that 6-shogaol prevented LPS-induced impairment in antioxidant enzymes and elevation in malondialdehyde level in the liver. The hepatic inflammatory response was significantly suppressed by 6-shogaol through suppressing the MAPK/NFκB pathway. RNA-sequencing data analysis revealed that 41 overlapped genes between the LPS vs. control group and 6-shogaol vs. LPS group were identified, among which 36 genes were upregulated, and 5 genes were downregulated for the LPS vs. control group. These overlapped genes are enriched in inflammation-related pathways, e.g., TNF and NFκB. The mRNA expression of the overlapped genes was also verified in the LPS-induced BRL-3A cell model. In summary, 6-shogaol shows great potential as a natural chemopreventive agent to treat sepsis-associated hepatic disorders.

Keywords: 6-shogaol; LPS; MAPK pathway; NFκB pathway; RNA sequencing; liver injury.

MeSH terms

  • Animals
  • Biomarkers
  • Catechols / pharmacology*
  • Computational Biology / methods
  • Disease Management
  • Disease Models, Animal
  • Disease Susceptibility
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Liver Diseases / drug therapy
  • Liver Diseases / etiology*
  • Liver Diseases / metabolism*
  • Liver Diseases / pathology
  • Liver Function Tests
  • Mice
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Sepsis / complications*
  • Signal Transduction / drug effects
  • Transcription, Genetic
  • Transcriptome

Substances

  • Biomarkers
  • Catechols
  • NF-kappa B
  • shogaol