Schizandrin B Mitigates Rifampicin-Induced Liver Injury by Inhibiting Endoplasmic Reticulum Stress

Biol Pharm Bull. 2020 Jan 1;43(1):145-152. doi: 10.1248/bpb.b19-00725. Epub 2019 Oct 30.

Abstract

Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.

Keywords: L02 cell; cell injury; endoplasmic reticulum stress; rifampicin; schizandrin B.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Chemical and Drug Induced Liver Injury, Chronic / metabolism
  • Chemical and Drug Induced Liver Injury, Chronic / prevention & control*
  • Cyclooctanes / isolation & purification
  • Cyclooctanes / pharmacology
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects*
  • Endoplasmic Reticulum Stress / genetics
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Lignans / isolation & purification
  • Lignans / pharmacology*
  • Polycyclic Compounds / isolation & purification
  • Polycyclic Compounds / pharmacology*
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Schisandra / chemistry

Substances

  • Cyclooctanes
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Lignans
  • Polycyclic Compounds
  • Protective Agents
  • schizandrin B