Systems Metabolic Insights into Kaempferol-Mediated Alleviation of Alcoholic Fatty Liver Disease

Chenmeng Song¹Lijia Li¹Jia Li¹Jengyuan Yao^1,2*

• ¹School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, China
• ²Key laboratory of functional and clinical translational medicine, Fujian province university, Xiamen Medical College, Xiamen, China

Alcoholic fatty liver disease is a significant global health concern caused by chronic and excessive alcohol intake, leading to hepatic steatosis, inflammation, and metabolic disruption. In this study, we investigated how kaempferol, a dietary flavonoid, mitigates ethanol-induced liver damage using a systems metabolic approach. Mice (n=12 per group) were randomly assigned to a control (CTRL) or ethanol-fed (AFLD) group, with or without kaempferol supplementation (20 mg/kg/day). Serum analyses revealed significantly lower levels of alanine aminotransferase (ALT, p < 0.0001) and aspartate aminotransferase (AST, p < 0.05) in kaempferol-treated mice, indicating reduced liver injury. Histological examination showed fewer lipid droplets and improved hepatic architecture in the kaempferol-treated group. Metabolomic profiling identified multiple altered metabolites associated with pathways such as glycolysis, amino acid metabolism, and sphingolipid signaling, suggesting broad-spectrum effects on metabolic homeostasis. In addition, kaempferol administration enhanced antioxidant defenses, as indicated by significantly decreased malondialdehyde (MDA, p < 0.05) and improved activities of antioxidant enzymes. Collectively, these findings highlight kaempferol’s potential as a multifunctional agent that systematically addresses metabolic and oxidative imbalances in alcoholic fatty liver disease, thereby offering a promising strategy for dietary-based liver protection.