7‐Hydroxyflavone improves nonalcoholic fatty liver disease by acting on STK24

Abstract The escalating incidence of nonalcoholic fatty liver disease (NAFLD) is closely associated with a high‐fat diet, leading to a decline in quality of life and significant health impairment. 7‐Hydroxyflavone (7‐HY) is a flavonoid known for its anti‐inflammatory, anticarcinogenic, and antioxidant effects. This study aims to assess the ameliorative effects of 7‐HY on NAFLD induced by a high‐fat diet and elucidate underlying mechanisms. Oleic acid/palmitic acid‐induced HepG2 cells and C57BL/6 mice on a high‐fat diet were utilized as in vitro and in vivo models. In animal experiments, 7‐HY was utilized as a dietary supplement. The 15‐week in vivo experiment monitored body weight, body fat percentage, glucose tolerance, insulin tolerance, and metabolic indexes. Commercial kits assessed triglyceride (TG) and total cholesterol levels in cells, liver tissue, and blood. Discovery Studio identified potential targets of 7‐HY, compared with NAFLD‐associated targets in the GeneCards database. Results indicated 7‐HY mitigated fat accumulation, hepatic steatosis, and oxidative stress induced by a high‐fat diet. Furthermore, 7‐HY showed potential efficacy in ameliorating abnormal glucose metabolism and promoting energy metabolism. Reverse target finding and molecular docking demonstrated a robust interaction between 7‐HY and serine/threonine kinase 24 (STK24). Subsequent experimental results confirmed 7‐HY's ability to inhibit TG deposition in HepG2 cells through interaction with STK24. In conclusion, 7‐HY demonstrated the capacity to alleviate high‐fat diet‐induced NAFLD, presenting a novel strategy for the prevention and treatment of NAFLD.