Catalpol reduces liver toxicity of triptolide in mice by inhibiting hepatocyte ferroptosis through the SLC7A11/GPX4 pathway: testing the Fuzheng Zhidu theory for detoxification.
10.12122/j.issn.1673-4254.2025.04.16
- Author:
Linluo ZHANG
1
;
Changqing LI
2
;
Lingling HUANG
3
;
Xueping ZHOU
2
;
Yuanyuan LOU
1
Author Information
1. Rehabilitation College in Jiangsu College of Nursing, Huai'an 223000, China.
2. First Clinical School of Nanjing University of Chinese Medicine, Nanjing 210009, China.
3. Department of Traditional Chinese Medicine, Affiliated Huai'an First People's Hospital of Nanjing Medical University, Huai'an 223300, China.
- Publication Type:Journal Article
- Keywords:
catalpol;
ferroptosis;
hepatotoxicity;
triptolide
- MeSH:
Animals;
Phenanthrenes/toxicity*;
Ferroptosis/drug effects*;
Diterpenes/toxicity*;
Epoxy Compounds/toxicity*;
Mice, Inbred C57BL;
Hepatocytes/metabolism*;
Mice;
Phospholipid Hydroperoxide Glutathione Peroxidase;
Iridoid Glucosides/pharmacology*;
Liver/metabolism*;
Chemical and Drug Induced Liver Injury/prevention & control*;
Male;
Amino Acid Transport System y+/metabolism*
- From:
Journal of Southern Medical University
2025;45(4):810-818
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification.
METHODS:C57BL/6J mice were randomized into blank control group, catalpol group, triptolide group and triptolide+catalpol group. After 13 days of treatment with the agents by gavage, the mice were examined for liver tissue pathology, liver function, hepatocyte subcellular structure, lipid peroxidation, ferrous ion deposition and expressions of ferroptosis-related proteins in the liver. In a liver cell line HL7702, the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions, Fe2+ concentration, lipid peroxidation, ROS level and the ferroptosis-related proteins.
RESULTS:In C57BL/6J mice, catalpol significantly alleviated triptolide-induced hepatic injury, lowered the levels of ALT, AST and LDH, and reversed the elevation of Fe2+ concentration and MDA level and the reduction of GPX level. In HL7702 cells, inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT, AST and LDH levels. Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11, FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells.
CONCLUSIONS:The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
