The antihyperuricemic and nephroprotective effect of puerarin by reducing uric acid level and exerting anti-inflammatory activity

Hyperuricemia (HUA) is a common metabolic disease and kidney injury is one of its main complications. As a typical natural flavonoid, puerarin (PEA) has a range of pharmacological activity but the antihyperuricemic mechanism of PEA has not been reported. Herein, the inhibitory activity of PEA against xanthine oxidase (XOD) was evaluated by in vitro enzymatic reaction, and kinetic analysis, the antihyperuricemic activity, and nephroprotective effect of PEA were studied in HUA mice. The enzymatic reaction showed that the inhibitory effect of PEA (half maximal inhibitory concentration [IC₅₀] = 4.39 µmol/L) on XOD was at the same level as allopurinol (IC₅₀ = 4.05 µmol/L), and kinetic analysis indicated that PEA was a mixed competitive inhibitor. In vivo studies demonstrated that PEA exhibited excellent antihyperuricemic activity by inhibiting XOD and urate transporter 1 (URAT1), to reduce uric acid level. At the same time, PEA reduced the level of inflammatory cytokines and exerted significant nephroprotective effect through anti-inflammatory activity. Molecular docking indicated that PEA closely bind to both XOD and URAT1, which had the potential to become an inhibitor of XOD and URAT1. In summary, PEA has important application value in developing novel functional food and medicine for the treatment of HUA and its complications.