SAT-220 - Picroside II Regulates Cuproptosis to Alleviate Metabolic Dysfunction-Associated Steatotic Liver Disease

Objective: Picroside II, one of the main active components of the traditional Chinese medicine Picrorhiza scrophulariiflora (Hu Huang Lian), has been shown to ameliorate MASLD, but its precise mechanism of action remains incompletely understood.


Methods: AML12 cells were cultured in vitro and stimulated with free fatty acids (FFAs) to establish a MASLD cell model. Proteomic analysis was completed to find the molecular mechanism.Male C57BL/6J mice were fed a high-fat diet to establish a MASLD mouse model and then administered Picroside II (10 mg/kg) by gavage for 4 weeks. Liver ultrasonography, enzymatic assays of hepatic and cellular triglyceride (TG) content, and histological staining were used to evaluate liver morphology and echogenicity, the extent of intracellular lipid accumulation, microscopic structural changes of hepatocytes, and details of fatty degeneration, as well as liver function and histopathological alterations. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes.

Results:

Oil Red O staining and FFA measurements indicated that Picroside II treatment significantly reduced intracellular lipid deposition. Proteomic analysis in cell culture

showed that Picroside II treatment reduced the protein expression of FDX1 and LIAS.

Furthermore,Picroside II markedly attenuated hepatic steatosis in MASLD mice, improved liver function, and alleviated tissue injury. Western blotting and qRT-PCR showed that Picroside II downregulated FDX1 and LIAS expression, restored the lipoylation of dihydrolipoamide S-acetyltransferase (DLAT), and inhibited copper deposition.


Conclusion: Picroside II ameliorates MASLD by inhibiting the FDX1/LIAS pathway, suggesting that cuproptosis is a therapeutic target of Picroside II in the treatment of MASLD.

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