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

• Published in: Journal of pharmacological sciences Vol. 144; no. 3; pp. 172 - 182
• Main Authors: Kuo, Chan-Yen, Chiu, Valeria, Hsieh, Po-Chun, Huang, Chun-Yen, Huang, S. Joseph, Tzeng, I-Shiang, Tsai, Fu-Ming, Chen, Mao-Liang, Liu, Chien-Ting, Chen, Yi-Ru
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2020; Elsevier
• Subjects: Chrysophanol; ER stress; Ferroptosis; Hepatic stellate cells; Lipid reactive oxygen species; ER stress; Hepatic stellate cells; Ferroptosis; Lipid reactive oxygen species; Chrysophanol
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2020.07.014

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.