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Transcriptomic analyses reveal the molecular mechanisms of schisandrin B alleviates CCl 4 -induced liver fibrosis in rats by RNA-sequencing.
- Source :
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Chemico-biological interactions [Chem Biol Interact] 2019 Aug 25; Vol. 309, pp. 108675. Date of Electronic Publication: 2019 May 28. - Publication Year :
- 2019
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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 CCl <subscript>4</subscript> -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 CCl <subscript>4</subscript> -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 CCl <subscript>4</subscript> -induced liver fibrosis by multiple modulatory mechanisms, which provide new clues for further pharmacological study of Sch B.<br /> (Copyright © 2019. Published by Elsevier B.V.)
- Subjects :
- 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 therapeutic use
Liver drug effects
Liver pathology
Liver Cirrhosis chemically induced
Liver Cirrhosis drug therapy
Liver Cirrhosis metabolism
Male
Medicine, Chinese Traditional
Polycyclic Compounds chemistry
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
Up-Regulation drug effects
Lignans pharmacology
Liver metabolism
Liver Cirrhosis pathology
Polycyclic Compounds pharmacology
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 309
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 31150632
- Full Text :
- https://doi.org/10.1016/j.cbi.2019.05.041