Houttuynia cordata traditional extract regulates uric acid transporter and reduces xanthine oxidase activity in hyperuricemic mice

• H. cordata extracts significantly reduce uric acid levels in both in vitro and in vivo models, inhibiting uric acid absorption and overproduction in hyperuricemia. • H. cordata inhibits xanthine oxidase (XO) activity in the liver and modulates renal uric acid transporters, including increasing the expression of OAT1 and ABCG2 while decreasing GLUT9, promoting uric acid excretion. • Renal histopathological damage in hyperuricemia mice is alleviated by H. cordata in a dose-dependent manner, suggesting potential nephroprotective effects. • Flavonoids are identified as the major bioactive components of H. cordata, and network pharmacology analysis reveals that its uric acid-lowering effect is likely mediated through anti-inflammatory mechanisms. Houttuynia cordata Thunb (H.cordata) is a common edible and medicinal plant that has attracted attention due to its rich bioactive compounds. In recent years, the incidence of hyperuricemia (HUA) has been increasing, prompting research into the potential role of natural plants in regulating uric acid levels. This study aims to explore the effects of H.cordata extracts on hyperuricemia both in vivo and in vitro . The results of the uric acid (UA) overproduction and absorption cell models showed that H.cordata could significantly inhibit the absorption of intracellular UA and also had a tendency to inhibit the production of UA. HUA mice induced by yeast and potassium oxonate results showed that blood UA was decreased and urine UA was increased both in a dose-dependent manner by H.cordata. H.cordata significantly reduced UA production by inhibiting the hepatic xanthine oxidase activity and increased UA excretion by decreasing the mRNA expression of glucose transporter 9 and increasing the mRNA expression of organic anion transporter 1 and ATP Binding Cassette Subfamily G Member 2 in kidney. Furthermore, renal histopathological damage was also alleviated by H.cordata in a dose-dependent manner. Additionally, Main components of H.cordata water extracts were flavonoids by High-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry/Mass Spectrometry. Network pharmacology results showed that flavonoid components of H.cordata may exert uric acid-lowering effects through anti-inflammatory. This study provided evidence demonstrating the effects of H.cordata extracts on alleviating UA levels in the HUA mice model, offering novel insights into the pharmacological effects and promoting the application of H.cordata. This study highlights the potential of H.cordata as a dietary supplement to alleviate HUA and kidney damage caused by HUA.