Antihyperuricemic and Nephroprotective Effects of the Total Flavonoids from Carya cathayensis Leaves(CCTF)in Potassium Oxonate/hypoxanthine-induced Hyperuricemic Mice

Background:Abnormally high level of uric acid in the blood,defined as hyperuricemia(HUA),increases the chance of developing various disorders,such as gout,hypertension,and diabetes.There is a critical need to create safer and more potent therapeutic medications since the current clinical treatment for HUA has a number of negative effects.Objective:To explore the antihyperuricemic benefits of the total flavonoids from Carya cathayensis leaves(CCTF)in HUA model mice and to elucidate the underlying mechanisms.Methods:The mouse HUA model was induced with potassium oxonate and hypoxanthine and then the mice were given normal saline,allopurinol,or various dosages of CCTF for one week.The weight of the mice was recorded,followed by measurements of their blood uric acid(UA),creatinine(Cr),urea nitrogen(BUN),aspar-tate aminotransferase(AST),alanine aminotransferase(ALT),and xanthine oxidase(XOD)activity.Hematoxylin and eosin(H&E)staining and Manson staining were used to simultaneously detect pathological abnormalities in the liver and kidney tissues.Afterward,the mRNA expression of urate transporters in kidney was determined by qRT‒PCR experiments,including ATP-binding cassette transporter subfamily G member 2(Abcg2),urate trans-porter 1(Urat1),and glucose transporter 9(Glut9).Finally,immunohistochemistry(IHC)staining was performed to confirm ABCG2 protein expression in the kidney.Results:In contrast to the model group,the CCTF group lowered blood levels of UA,Cr,BUN,ALT,and AST in serum,downregulated XOD levels in serum and liver,and significantly improved liver and renal damage,exhibiting outstanding antihyperuricemic effects.The levels of Urat1 and Glut9 were further shown to be much lower in the kidney,whereas both Abcg2 expression and ABCG2 level were increased,according to the findings.Conclusion:CCTF ameliorated hyperuricemia-related kidney damage and had antihyperuricemic effects,suggest-ing that CCTF might have the potential to protect against HUA by regulating the expression of relative urate transporters and XOD.