Study on prophylactic effects and mechanism of Tongfeng Kangning Tables on hyperuricemia
Objective To evaluate of Tongfeng Kangning Tables(TKT)in the prophylactic effect and mechanism study of hyperuricemia in various experimental models.Methods A rat model of hyperuricemia was established using ig administration yeast extract in combination with ip potassium oxonate.Yeast extract(20 g·kg-1)was ig administered for seven consecutive days,and drug administration initiated on the 5th d of yeast extract gavage,groups included a control group,a model group,low,medium,and high dose TKT groups(0.58,1.15,2.30 g·kg-1),and a benzbromarone 27 mg·kg-1 group,the control and model groups received an equal volume of 0.5%CMC-Na daily via ig administration.On the 3rd d of drug administration(the 7th d of ig yeast extract),potassium oxonate at 200 mg·kg-1 was ip injected to induce the model.The preventive effect and mechanism of action of TKT on rat hyperuricemia were evaluated by measuring serum uric acid concentrations,urine volume,uric acid excretion in urine,at 2 h and 4 h post-injection of potassium oxonate,and the expression of URAT1,OAT1,and OAT3 antibodies in the kidneys on the 4th d of drug administration.A mice model of hyperuricemia was induced with hypoxanthine,groups consisted of control group,model group,low-,mid-,and high-dose TKT groups(0.83,1.66,3.33 g·kg-1),and a benzbromarone 39 mg·kg-1 group.These were orally administered once daily for 5 d,with control and model groups receiving an equivalent volume of 0.5%CMC-Na,the preventive effect of TKT against hyperuricemia in mice was assessed through measurements of blood uric acid levels,uricase,and XOD content.A water load model in rats was employed with groups including a control group,low,medium,and high dose TKT groups(0.58,1.15,2.30 g·kg-1),and hydrochlorothiazide 27 mg·kg-1 group.Each group was administered their respective treatments orally once daily for 3 d,while the control group received an equal volume of 0.5%CMC-Na.The diuretic effect of TKT in rats was evaluated by measuring urine volume at 1,2,3,4,and 5 h post-administration,as well as the total urine output within the first 5 h.Results Compared with the model group,TKT groups were significantly reduced serum uric acid(P<0.05,0.01),increased the excretion of uric acid in urine,significantly increased the expression of organic anion transporter 1(OAT1)and decreased urate transporter 1(URAT1)in rats kidney(P<0.05,0.01).TKT 1.66 and 3.33 g·kg-1 could significantly reduce serum uric acid(P<0.05,0.01),0.83,1.66 and 3.33 g·kg-1 increased the uricase level in mice(P<0.05,0.01).TKT 0.58,1.15,and 2.30 g·kg-1 could obviously increase the urine volume at different time points and the total urine volume from 1 to 5 h after administration(P<0.05,0.01).Conclusion TKT reduced the concentration of serum uric acid and increased the excretion of urinary uric acid by promoted the excretion of uric acid,inhibited its reabsorption,and diuretic actions,which demonstrated significant prophylactic efficacy in experimental hyperuricemia.