Transcriptomic analyses reveal the molecular mechanisms of schisandrin B alleviates CCl4-induced liver fibrosis in rats by RNA-sequencing

Chem Biol Interact. 2019 Aug 25:309:108675. doi: 10.1016/j.cbi.2019.05.041. Epub 2019 May 28.

Abstract

Liver fibrosis is a progression of chronic liver disease with lacks effective therapies at present. Schisandrin B (Sch B), a bioactive compound extracted from the traditional Chinese medicine Schisandra chinensis, was reported to benefit liver diseases. This study aimed to investigate the therapeutic effects and molecular mechanisms of Sch B against CCl4-induced liver fibrosis in rats. RNA sequencing and transcriptome analysis were performed collaboratively, including analysis of differential gene expression, gene ontology (GO) analysis, pathway analysis and pathway-act-network analysis. The results demonstrated that Sch B effectively alleviated CCl4-induced liver damage and fibrosis in rats, as evidenced by improved liver function and decreased extracellular matrix deposition. Furthermore, 4440 (1878 up-regulated, 2562 down-regulated) genes in the model group versus (vs) normal group, 4243 (2584 up-regulated, 1659 down-regulated) genes in Sch B-treated group vs model group were identified as differentially expressed genes (DEGs). Subsequently, GO analysis revealed that DEGs were mainly enriched in metabolism, oxidation-reduction, endoplasmic reticulum stress and apoptosis-related biological processes. Pathway analysis suggested that Sch B up-regulated cytochrome P450 drug metabolism, PPAR signaling pathways, and down-regulated glutathione metabolism pathways. In addition, the regulatory patterns of Sch B on key genes and pathways were also confirmed. In conclusion, our study demonstrated Sch B alleviated CCl4-induced liver fibrosis by multiple modulatory mechanisms, which provide new clues for further pharmacological study of Sch B.

Keywords: Apoptosis; Endoplasmic reticulum stress; Liver fibrosis; RNA-Sequencing; Schisandrin B.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carbon Tetrachloride / toxicity
  • Cyclooctanes / chemistry
  • Cyclooctanes / pharmacology
  • Cyclooctanes / therapeutic use
  • Down-Regulation / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Gene Expression Profiling
  • Lignans / chemistry
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Male
  • Medicine, Chinese Traditional
  • Polycyclic Compounds / chemistry
  • Polycyclic Compounds / pharmacology*
  • Polycyclic Compounds / therapeutic use
  • RNA / chemistry
  • RNA / isolation & purification
  • RNA / metabolism
  • Rats
  • Rats, Wistar
  • Schisandra / chemistry
  • Schisandra / metabolism
  • Sequence Analysis, RNA
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transcriptome*
  • Up-Regulation / drug effects

Substances

  • Cyclooctanes
  • Lignans
  • Polycyclic Compounds
  • schizandrin B
  • RNA
  • Carbon Tetrachloride