Atractylodes macrocephala water extract exerts a protective effect against high fat and high sugar diet-induced NAFLD by inhibiting the TRAF1/ASK1/JNK pathway

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health issue, making early prevention and treatment are crucial. Atractylodes macrocephala, as a functional food, holds potential in improving liver metabolic diseases. The aim of this study was to investigate whether A. macrocephala water extract (AMW) has a preventive effect on NAFLD induced by high-fat, high-sugar (HSHF) diet. Initially, the components of AMW were analyzed, revealing the high content of polysaccharides and lactones as its main constituents. Mice were then subjected to HSHF diet and administered AMW for 12 weeks to observe its effects on glucose and lipid metabolism, hepatic lipid accumulation, oxidative damage, inflammatory injury, and apoptosis. The results indicated that AMW significantly improved glucose and lipid metabolism disorders in mice, reduced hepatic lipid accumulation, oxidative damage, and inflammatory injury. Specifically, AMW notably decreased the release of tumor necrosis factor-alpha (TNF-α), thereby inhibiting the activation of the hepatic TRAF1/ASK1/JNK pathway, which alleviated the progression of inflammatory responses. Additionally, c-Jun N-terminal kinase (JNK) phosphorylation was reduced, inhibiting the activation of downstream factor activates protein kinase B (AKT), which in turn led to decreased expression of apoptosis-related factors such as Bcl-2-associated X protein (Bax), cytochrome C (Cyt C), and Cleaved Caspase-3, while increasing B-cell lymphoma-2 (Bcl-2) expression. These findings suggest that AMW may protect against HSHF-induced NAFLD by reducing hepatic oxidative damage, inhibiting inflammation, and preventing apoptosis, potentially through inhibition of the TRAF1/ASK1/JNK pathway.