Catalpol reduces liver toxicity of triptolide in mice by inhibiting hepatocyte ferroptosis through the SLC7A11/GPX4 pathway:testing the Fuzheng Zhidu theory for detoxification
ZHANG Linluo
LI Changqing
HUANG Lingling
ZHOU Xueping
LOU Yuanyuan
Abstract：Objective 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.Conclusion The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
Keywords：catalpoltriptolidehepatotoxicityferroptosis
Publication Date：2025-04-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 810-818 )