Hyperuricemia (HUA) is a metabolic disorder with an increasing prevalence rate in last decade. Although secoisolariciresinol diglucoside (SDG) from flaxseed was reported to have anti-inflammatory effects, its role and action mechanism in alleviating HUA remain unclear. This study investigated the effect of SDG on reducing uric acid (UA) in mice with HUA induced by potassium oxonate (PO) and hypoxanthine. The results showed that oral administration of SDG at 300 mg/kg significantly reduced UA levels by 75.37 ± 4.05 % and suppressed hepatic xanthine oxidase (XOD) gene expression by 50.99 ± 2.72 % compared to the model group, accompanied by amelioration of structural abnormalities in the liver, kidneys, and intestines. This urate-lowering effect was associated with renal transporter modulation: ABCG2 protein expression increased by 67.72 ± 11.22 %, while OAT1 expression surged by 175.90 ± 18.34 %. Meanwhile, the levels of GLUT9, URAT1 were downregulated by 19.12 ± 1.47 % and 63.73 ± 2.54 %, respectively. Intestinal ABCG2 expression was further upregulated by 62.21 ± 1.16 %, and GLUT9 mRNA levels decreased by 84.15 ± 4.12 %, collectively improving UA excretory dysfunction. Besides, SDG alleviated UA-induced intestinal injury, preserved epithelial integrity, and upregulated the expression of tight junction proteins (including ZO-1 and occludin) through the inhibition of the TLR4/ NF-κB signaling pathway, thereby contributing to the protection of intestinal immune barrier. SDG ameliorated UA-disrupted purine metabolism and bile acid secretion by increasing the abundance of beneficial bacteria (e.g., Alistipes, Prevotellaceae_UCG-001, and Ruminococcus) and decreasing the abundance of pathogenic genera (e.g., Parabacteroides, Bacteroides, and Desulfovibio). Hence, SDG showed its potential to become a natural functional ingredient for HUA amelioration.
Link to Full TextFood Res Int., 2025, Oct;217:116770. doi: 10.1016/j.foodres.2025.116770