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Clusterin in Disease Pathology / Ferroptosis and Cancer Prognosis · Journal article
Frontiers in Pharmacology · August 7, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a mechanistic preclinical study demonstrating that wogonoside (WOG), a flavonoid compound, reduces hepatic steatosis, oxidative stress, and ferroptosis-associated injury in diet-induced MASH mouse models and FFA-treated hepatocyte cell cultures. The compound's effects appear mediated by AMPK activation and restoration of the xCT/GPX4 antioxidant axis, but clinical efficacy and safety in humans remain unestablished.
Preclinical experimental study using diet-induced animal model and cell culture. HFFD-fed mice (specific age, strain details, and cohort size not reported) and HepG2 human hepatocellular carcinoma cell line treated with free fatty acids. Intervention: Wogonoside (WOG), a flavonoid isolated from Scutellaria baicalensis, administered to HFFD-fed mice and FFA-treated HepG2 cells. Compared with: Standard HFFD-fed control mice without WOG; untreated FFA-induced HepG2 cells; ferrostatin-1 and erastin used as positive and negative controls for ferroptosis experiments.
WOG ameliorated HFFD-induced obesity, hepatic steatosis, hepatocellular ballooning, liver injury, dyslipidemia, insulin resistance, oxidative stress, and inflammatory responses in mice WOG increased AMPK phosphorylation and upregulated PGC-1α, PPARα, and CPT-1 while reducing SREBP-1c and lipogenic proteins (ACLY, ACACA, FASN, SCD-1) in liver tissue and FFA-treated HepG2 cells WOG decreased Fe 2+ accumulation, lipid peroxidation, restored glutathione homeostasis, and increased xCT and GPX4 expression in vivo and in vitro
No report of adverse effects or safety margins in animal studies
These findings are preclinical and suggest wogonoside warrants investigation in human trials for MASH. However, efficacy and safety in patients cannot be inferred from animal models alone; clinical translation requires appropriate regulatory pathways and human studies.
Preclinical study in animal and cell models with mechanistic endpoints; no human trials reported, limiting clinical applicability despite sound experimental design.
As stated by the source record.
Quoted from the source exactly as published.
These findings are preclinical and suggest wogonoside warrants investigation in human trials for MASH. However, efficacy and safety in patients cannot be inferred from animal models alone; clinical translation requires appropriate regulatory pathways and human studies.
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Background Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease with limited pharmacological treatment options. Wogonoside (WOG), a flavonoid isolated from Scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and lipid-lowering activities; however, its effects and underlying mechanisms in MASH remain unclear. Methods A high-fat and high-fructose diet (HFFD)-induced mouse model of MASH and free fatty acid (FFA)-induced HepG2 cell steatosis model were used to evaluate the hepatoprotective effects of WOG. Liver histopathology, serum biochemical parameters, glucose tolerance, lipid accumulation, oxidative stress, ferroptosis-associated indicators, transcriptomic profiling, and expression of relevant proteins were assessed. The anti-ferroptotic effects of WOG were further examined using erastin and ferrostatin-1 in HepG2 cells. Results WOG administration ameliorated HFFD-induced obesity, hepatic steatosis, hepatocellular ballooning, liver injury, dyslipidemia, insulin resistance, oxidative stress, and inflammatory responses in mice. Transcriptomic analysis indicated that WOG-responsive genes were enriched in lipid metabolism, peroxisome proliferator-activated receptor signaling, AMPK signaling, and ferroptosis-related pathways. In liver tissues and FFA-treated HepG2 cells, WOG increased AMPK phosphorylation and upregulated the expression of PGC-1α, PPARα, and CPT-1, while reducing the expression of SREBP-1c and its downstream lipogenic proteins, including ACLY, ACACA, FASN, and SCD-1. These changes were accompanied by decreased hepatic and intracellular triglyceride accumulation. In addition, WOG reduced reactive oxygen species, restored mitochondrial membrane potential, increased Nrf2 and HO-1 expression, and attenuated inflammatory responses. WOG also decreased Fe 2+ accumulation and lipid peroxidation, restored glutathione homeostasis, and increased xCT and GPX4 expression in vivo and in vitro. Moreover, WOG counteracted erastin-induced ferroptosis-related changes and exhibited effects similar to those of ferrostatin-1 in FFA-treated HepG2 cells. Conclusion WOG alleviates experimental MASH by improving hepatic lipid metabolic homeostasis and suppressing ferroptosis-associated injury. These protective effects are associated with activation of AMPK signaling and restoration of the xCT/GPX4 antioxidant defense axis. WOG may therefore represent a promising candidate for the pharmacological management of MASH.
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