Gandou Fumu Decoction improves liver steatosis by inhibiting hepatocyte ferroptosis in mice with Wilson's disease through the GPX4/ACSL4/ALOX15 signaling pathway.
10.12122/j.issn.1673-4254.2025.07.13
- Author:
Mengying ZHANG
1
;
Chenling ZHAO
1
;
Liwei TIAN
1
;
Guofang YU
1
;
Wenming YANG
1
;
Ting DONG
1
Author Information
1. Encephalopathy Center, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
- Publication Type:Journal Article
- Keywords:
Gandou Fumu Decoction;
ferroptosis;
steatosis of the liver;
wilson's diseast
- MeSH:
Animals;
Ferroptosis/drug effects*;
Mice;
Signal Transduction/drug effects*;
Drugs, Chinese Herbal/therapeutic use*;
Hepatolenticular Degeneration/drug therapy*;
Hepatocytes/metabolism*;
Phospholipid Hydroperoxide Glutathione Peroxidase;
Fatty Liver/metabolism*;
Arachidonate 15-Lipoxygenase/metabolism*;
Coenzyme A Ligases/metabolism*;
Liver/metabolism*;
Male
- From:
Journal of Southern Medical University
2025;45(7):1471-1478
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice.
METHODS:With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe2+, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress.
RESULTS:The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe2+, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe2+, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions.
CONCLUSIONS:GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
