Flavonoid extract of saffron by-product alleviates hyperuricemia via inhibiting xanthine oxidase and modulating gut microbiota.

Hyperuricemia was associated with the overproduction or inadequate excretion of uric acid, while its association with gut microbiota has emerged although few studies were focused on it. Previously, we have reported a flavonoid extract from saffron floral bio-residues lowered uric acid in potassium oxonate-induced hyperuricemic mice. In this study, the impacts of the flavonoid extract on potassium oxonate-induced hyperuricemic rats were evaluated through its effects on serum, renal, intestinal uric acid, and xanthine oxidase activity. At the same time, the microbial and metabolic features of the flavonoid extract against hyperuricemia were explored using 16S rRNA sequencing techniques and serum metabolomics, respectively. According to the results, the flavonoid extract lowered serum and intestinal uric acid levels in hyperuricemic rats without kidney damage. On the one hand, it inhibited serum and liver xanthine oxidase activities and down-regulated the expression of hepatic xanthine oxidase. On the other hand, it ameliorated the hyperuricemia-associated gut microbiota dysbiosis and alleviated the disturbance of serum metabolome, especially of lipid and amino acid metabolites. The results suggested that the flavonoid extract of saffron floral bio-residues exerts a potent antihyperuricemia effect by inhibiting xanthine oxidase to decrease uric acid production and modulating gut microbiota related to host metabolism.