Integration of transcriptomics and metabolomics confirmed hepatoprotective effects of steamed shoot extracts of ginseng (Panax ginseng C.A. Meyer) on toxicity caused by overdosed acetaminophen

Biomed Pharmacother. 2021 Nov:143:112177. doi: 10.1016/j.biopha.2021.112177. Epub 2021 Sep 20.

Abstract

The study aimed, by integrating transcriptomics and metabolomics, to reveal novel biomarkers caused by overdosed acetaminophen (APAP) and liver protection substances procured by pre-administration of ginseng shoots extract (GSE). Totally 4918 genes and 127 metabolites were identified as differentially expressed genes and differential metabolites, respectively. According to KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, such pathways as primary bile acid biosynthesis, bile secretion, retinol metabolism, histidine and several other amino-related metabolism were significantly altered by GSE and disturbed by subsequent overdosed APAP at the transcriptomic as well as metabolomic levels. Fifteen key biomarker metabolites related to these pathways were up-regulated in APAP-treated vs GSE-pretreated liver tissues, and were reported exerting anti-oxidant, anti-inflammatory, anti-apoptotic and/or immunomodulate functions, three of which even possessed direct hepatoprotection effects. Twenty five vital unigenes modulating these metabolites were further verified by correlation analysis and expression levels of fifteen of them were examined by qRT-PCR. Our findings indicate that GSE may be an effective dietary supplement for preventing the liver damage caused by the overdosed APAP.

Keywords: APAP-induced liver injury; Hepatoprotection biomarkers; Metabolomics; Steamed ginseng shoot extract (GSE); Transcriptomics.

MeSH terms

  • Acetaminophen
  • Amino Acids / metabolism
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Bile Acids and Salts / metabolism
  • Biomarkers / metabolism
  • Chemical and Drug Induced Liver Injury / genetics
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Disease Models, Animal
  • Drug Overdose
  • Gene Expression Profiling*
  • Immunomodulating Agents / isolation & purification
  • Immunomodulating Agents / pharmacology
  • Inflammation Mediators / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Metabolome*
  • Metabolomics*
  • Mice
  • Oxidative Stress / drug effects
  • Panax* / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Shoots
  • Steam
  • Transcriptome*
  • Vitamin A / metabolism

Substances

  • Amino Acids
  • Anti-Inflammatory Agents
  • Antioxidants
  • Bile Acids and Salts
  • Biomarkers
  • Immunomodulating Agents
  • Inflammation Mediators
  • Plant Extracts
  • Steam
  • Vitamin A
  • Acetaminophen