Isoliquiritigenin alleviates liver fibrosis through caveolin-1-mediated hepatic stellate cells ferroptosis in zebrafish and mice

Phytomedicine. 2022 Jul:101:154117. doi: 10.1016/j.phymed.2022.154117. Epub 2022 Apr 20.


Background: Liver fibrosis is a major disease that threatens people's health around the world. However, there is a lack of effective treatment to completely reverse liver fibrosis. Liver transplantation is currently the only curative option for patients with advanced cirrhosis. Ferroptosis is a newly discovered type of cell death and plays an important role in the process of liver fibrosis, but the specific mechanism needs to be clarified.

Hypothesis/purpose: To explore the regulatory mechanism of isoliquiritigenin (ISL) in the process of liver fibrosis and the relationship between Cav-1 and ferroptosis.

Methods: In this research, zebrafish, HSC-T6 cells, and mice were used as the research object. Different ROS probes to visually detect the content and distribution of ROS in live zebrafish and cells. Lentivirus and siRNA-mediated transfection techniques were used for the construction of Cav-1 overexpression and knockdown cell lines to verify the important role of Cav-1 in vitro.

Results: Generally, we first elucidated that ISL relieved liver fibrosis by inducing hepatic stellate cells (HSCs) ferroptosis through repressing GPX4 expression and increasing the expression of TFR and DMT1, thus producing a large number of ROS, we also found that Cav-1 exerted its anti-hepatic fibrosis effect by promoting HSCs ferroptosis.

Conclusion: Our results have shown that Cav-1-mediated HSCs ferroptosis is necessary for ISL to play an anti-fibrotic effect in vitro and in vivo.

Keywords: Cav-1; Ferroptosis; Hepatic stellate cells; Isoliquiritigenin; Liver fibrosis; ROS.

MeSH terms

  • Animals
  • Caveolin 1 / metabolism
  • Chalcones
  • Ferroptosis*
  • Hepatic Stellate Cells* / metabolism
  • Humans
  • Liver / metabolism
  • Liver Cirrhosis / metabolism
  • Mice
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Zebrafish / metabolism


  • Caveolin 1
  • Chalcones
  • Reactive Oxygen Species
  • isoliquiritigenin