Weissella cibaria X1 fermentation enhances the UA-lowering ability of Carthamus tinctorius L. via metabolic regulation

The uric acid (UA) degrading Weissella cibaria X1 was employed for the fermentation of safflower ( Carthamus tinctorius L.). Compared with naturally fermented safflower, X1 fermented safflower significantly enhancing the antioxidant capacity and xanthine oxidase (XO) inhibition rate, decreased UA levels by 81.30%, XO activity by 99.02%, and creatinine levels by 27.08% based on a hyperuricemia (HUA) zebrafish model. Additionally, it upregulated the genes inhibiting UA synthesis—hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1 gene) 1.91 fold, and those promoting UA excretion—urate oxidase (UOX) gene 5.40 fold, organic anion transporter 1 (OAT1) gene 4.80 fold, hepatocyte nuclear factor 4 alpha (HNF4A gene) 3.29 fold, and polyvalent PDZ domain 1 (PDZK1) gene 57.46 fold. Subsequently, non-targeted metabolomics analysis showed that X1 fermentation downregulated the content of L-glutamine and modulated purine metabolism than the safflower fermented naturally, thus decreasing the levels of purines and increasing those of scolymoside. Our research provided a potential HUA therapy via both pharmaceutical and nutraceutical strategies.