Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis

J Pharmacol Sci. 2020 Nov;144(3):172-182. doi: 10.1016/j.jphs.2020.07.014. Epub 2020 Aug 6.

Abstract

Hepatitis B virus X protein (HBx) and hepatic stellate cells (HSCs) are critical for liver fibrosis development. Anti-fibrosis occurs via reversion to quiescent-type HSCs or clearance of HSCs via apoptosis or ferroptosis. We aimed to elucidate the role of chrysophanol in rat HSC-T6 cells expressing HBx and investigate whether chrysophanol (isolated from Rheum palmatum rhizomes) influences cell death via ferroptosis in vitro. Analysis of lipid reactive oxygen species (ROS), Bip, CHOP, p-IRE1α, GPX4, SLC7A11, α-SMA, and CTGF showed that chrysophanol attenuated HBx-repressed cell death. Chrysophanol can impair HBx-induced activation of HSCs via endoplasmic reticulum stress (ER stress) and ferroptosis-dependent and GPX4-independent pathways.

Keywords: Chrysophanol; ER stress; Ferroptosis; Hepatic stellate cells; Lipid reactive oxygen species.

MeSH terms

  • Animals
  • Anthraquinones / isolation & purification
  • Anthraquinones / pharmacology*
  • Anthraquinones / therapeutic use*
  • Cell Line
  • Endoplasmic Reticulum Stress / drug effects*
  • Ferroptosis / drug effects*
  • Fibrosis
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / etiology*
  • Phytotherapy*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Trans-Activators / adverse effects*
  • Viral Regulatory and Accessory Proteins / adverse effects*

Substances

  • Anthraquinones
  • Reactive Oxygen Species
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • chrysophanic acid