ABSTRACT:
To investigate the antioxidant effects and underlying mechanisms of
Ampelopsis grossedentata
flavonoids (AGF) in rats fed a high‐fat diet. In this study, we established a basal diet group, a high‐fat diet group, a high‐fat diet combined with Xuezhikang group, and high‐fat diet groups supplemented with low, medium, and high doses of AGF. After 7 weeks of feeding, relevant physiological antioxidant indicators and the antioxidant effects mediated by gut microbiota were measured. The results demonstrated that: (1) AGF significantly increased the gene expression, protein levels, and enzymatic activity of CAT and SOD in the livers of rats fed a high‐fat diet, thereby increasing the total antioxidant capacity and reducing power in serum. (2) Simultaneously, AGF demonstrated strong free radical (DPPH, hydroxyl, superoxide anion, and ABTS) scavenging capacity, accompanied by a reduction in hydrogen peroxide content and anti‐lipid peroxidation activity. (3) Furthermore, AGF significantly decreased the levels of pro‐inflammatory cytokines (IL‐6, IL‐1β, TNF‐α) in the livers of high‐fat diet‐fed rats. (4) Additionally, flavonoids enriched the diversity of gut microbiota, optimized microbial structure, and increased the abundance of beneficial microbes (such as
Akkermansia
,
Lactobacillus
,
Blautia
,
norank_f__Eubacterium_coprostanoligenes_group
,
Enterorhabdus
,
Butyricicoccus
, and
Clostridium_innocuum_group
), which showed positive correlations with antioxidant‐related physiological parameters. In conclusion, AGF significantly alleviated high‐fat diet‐induced oxidative stress and liver injury in rats, providing a theoretical foundation for developing H‐AGF as a functional ingredient for use in functional foods, pharmaceuticals, and skincare products.