Amelioration of MASLD via Umbelliferone through Modulation of Hepatic Metabolic Function and Restoration of Gut-Liver Axis Homeostasis

Metabolic dysfunction-associated steatotic liver disease (MASLD) lacks effective pharmacotherapies. This study evaluated the nutritional interventions of Umbelliferone (UMB), a natural coumarin from fruits, on MASLD using a combination of in vitro colonic fermentation, a high-fat diet (HFD)-induced mouse model, and oleic acid-treated HepG2 cells. Biochemical, histological, and molecular analyses were performed to evaluate metabolic and microbial changes. UMB exhibited prebiotic properties, enhancing microbial diversity and butyrate production. It significantly reduced serum lipids, ALT/AST levels, and hepatic steatosis in HFD-mice. In hepatocytes, UMB activated AMPK signaling, inhibiting lipogenesis and promoting fatty acid oxidation. Furthermore, UMB restored gut microbiota balance and increased short-chain fatty acids. These results indicate that UMB alleviates MASLD by modulating hepatic metabolic function and gut microbiota homeostasis, highlighting its dual therapeutic role targeting the gut–liver axis.