Hydroxysafflor yellow A alleviates oxidative stress and inflammatory damage in the livers of mice with nonalcoholic fatty liver disease and modulates gut microbiota.

Introduction: Hydroxysafflor yellow A (HSYA), its primary bioactive metabolite of Methods: NAFLD was induced in mice using a high-fat diet (HFD), followed by intragastric administration of hydroxysafflor yellow A (HSYA). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglycerides (TG) were quantified to evaluate liver function and lipid metabolism. Oxidative stress markers, including superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration, were also assessed. The pro-inflammatory cytokines IL-6, TNF-α, and IL-1β in serum were measured using ELISA. The hepatic expression of NLRP3 inflammasome and its downstream effector, Caspase-1, was analyzed by Western blot. Histopathological examination of liver tissues was performed using hematoxylin and eosin (H&E) staining to evaluate structural damage. Furthermore, alterations in the gut microbiota composition were characterized via 16S rDNA sequencing of fecal samples. Untargeted metabolomics was conducted to identify serum metabolic variations and elucidate enriched metabolic pathways associated with HSYA treatment. Results: HSYA significantly inhibited HFD-induced weight gain and alleviated liver inflammation. It reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides (TG) ( Discussion: HSYA demonstrates potent anti-inflammatory and antioxidant effects, effectively mitigating liver inflammation and oxidative stress in NAFLD mice. Its therapeutic mechanisms may involve modulating gut microbiota and regulating serum phenylalanine and tyrosine metabolism, offering insights into its potential as a treatment for NAFLD.