Mume Flos ameliorates MASLD-associated cognitive impairment by attenuating IL-17/NF-κB-mediated metabolic neuroinflammation.

Hepatic steatosis and persistent low-grade inflammation are the hallmarks of metabolic dysfunction-associated steatotic liver disease (MASLD), and extrahepatic complications, including cognitive impairment. However, the signaling mechanisms linking liver injury to neurological dysfunction remain incompletely understood. In this study, we investigated whether Mume Flos (MF) ameliorates MASLD and related cognitive impairment through modulation of the IL-17/ NF-κB signaling pathway. High-fat diet-fed mice and palmitic acid-treated HepG2 cells were used as in vivo and in vitro models of hepatic steatosis and lipid overload. MF treatment reduced hepatic lipid accumulation, improved serum liver enzyme levels, and suppressed systemic and hepatic inflammatory cytokine production. In parallel, MF alleviated anxiety-like behavior and improved learning and memory in MASLD mice, accompanied by reduced neuroinflammation in the hippocampus. In HepG2 cells, MF decreased intracellular lipid deposition and downregulated the expression of inflammatory mediators. Transcriptomic and WB analyses further demonstrated that MF markedly inhibited IL-17/NF-κB signaling in both liver and brain tissues. Collectively, these findings indicate that MF attenuates metabolic inflammation and improves liver-brain axis dysfunction in MASLD, at least in part, through suppression of IL-17/NF-κB signaling. This study identifies IL-17/NF-κB as a potential mechanistic link and therapeutic target in MASLD-associated hepatic and cognitive comorbidities.