Paecilomyces cicadae-fermented Radix astragali ameliorates hyperuricemia by modulating gut purine metabolism

Hyperuricemia (HUA) refers to a metabolic disorder arising from purine metabolic dysfunction, which is clinically defined by an abnormally increased serum uric acid (UA) concentration. Radix astragali is the root of Astragalus membranaceus (Fisch.) Bunge which acts as a diuretic to protect the kidneys. Radix astragali - Paecilomyces cicadae fermentation products (RPF) promises to be a candidate for lowering UA, whereas the underlying anti-hyperuricemic mechanisms in the gut remain unknown. This study explored the impact of RPF on potassium oxonate-induced HUA rats based on the gut microbiota and gut purine metabolism. Furthermore, DIA quantitative proteomics and targeted quantitative analysis of metabolites were used to investigate its effects on purine metabolism. The results showed that RPF (3 g/kg) administered for 28 days significantly reduced serum UA levels by 30%, decreased intestinal UA accumulation, and was associated with gut microbiota remodeling and alterations in intestinal purine metabolism. Meanwhile, RPF restored the abundance of Clostridium UCG-014 beneficial to host health. DIA quantitative proteomics revealed the purine metabolic pathways involving adenosine deaminase (ADA) and xanthine oxidase (XOD) are key targets for RPF in regulating intestinal UA metabolism. In particular, UA synthesis can be reduced by inhibiting the synthesis of UA precursors such as adenosine and inosine. Therefore, enhancing the degradation of purine-related substances by gut microbiota may be a strategy by which RPF prevents and treats HUA.