Astragaloside IV prevents liver fibrosis by blocking glycolysis-mediated macrophage M1 polarization

Hepatic fibrosis is a late-stage process of many chronic liver diseases. Blocking the fibrosis process will be beneficial to the treatment and recovery of the disease. Hepatic macrophages are a remarkably heterogeneous population of immune cells that play multiple functions in homeostasis and are central to liver fibrosis. Glycolysis-mediated macrophage metabolic reprogramming leads to an increase in the proportion of M1 macrophages and the release of pro-inflammatory cytokines. The present study aimed to investigate the therapeutic effect and mechanism of Astragaloside IV (AS-IV) against carbon tetrachloride (CCl₄)-induced liver fibrosis. The study found that AS-IV is an effective agent for reducing the production of inflammatory factors in CCl₄-induced liver fibrosis. It was also found that AS-IV blocks macrophage M1 polarization and relieves liver fibrosis. Mechanistically, AS-IV reduces the methylation level of the FoxO1 promoter region and then upregulates its expression. FoxO1 can inhibit the expression of key enzymes in the glycolysis pathway and block glycolysis-mediated macrophage M1 polarization. Our findings indicate that AS-IV is an attractive option for treating liver fibrosis.