RESUMO
OBJECTIVE To investigat e the effects of water extract （WCS）and ethanol extract （ECS）from the root of Caragana sinica on hyperuricemia （HUA）in mice. METHODS Kunming mice were randomly divided into normal control group ， model group ，allopurinol group （positive control ，5 mg/kg），benzbromarone group （positive control ，7.8 mg/kg），WCS low-dose ， medium-dose and high-dose groups （38，75，150 mg/kg），ECS low-dose ，medium-dose and high-dose groups （50，100，200 mg/kg）， with 10 mice in each group. Except for the normal control group ，the other mice were given potassium oxazinate intraperitoneally and hypoxanthine intragastrically for consecutive 7 d to establish HUA model. On the third day of modeling ，mice in each administration group were given corresponding drugs intragastrically ，and normal control group and model group were given equal volume of normal saline once a day for 5 consecutive days.The body weight of mice were weighted during administration ；one hour after the last administration ，the organ indexes of liver ，kidney and spleen were calculated ；the contents of serum uric acid （SUA）， blood urea nitrogen （BUN）and serum creatinine （SCR）；the activity of xanthine oxidase （XOD）in serum and liver tissue were determined. Relative mRNA and protein expressions of XOD in liver tissue ，relative expre ssions of GLUT9，URAT1 and OAT 1 in renal tissue were all detected ；and the pathological changes of renal tissue were observed. RESULTS There were no significant differences in liver index and spleen index in each group （P＞0.05）. Compared with normal control group ， except for allopurinol group ， there were no significant differences in the body weight and the contents of BUN and SCR in mice of other administration groups （P＞0.05）；the renal index and SUA content of mice in the m odel group and allopurinol group were significantly increased （P＜0.05）；in the model group ，the XOD activity in serum and liver tissue ，the relative mRNA and protein expression of XOD in liver tissue ，the relative expressions of GLUT 9 and URAT 1 protein in renal tissue were significantly increased （P＜0.05），and the relative expression of OAT 1 protein in renal tissue was significantly decreased （P＜ 0.05）. Compared with model group ，renal indexes of mice were decreased significantly in WCS and ECS groups （P＜0.05），and the pathological damage of renal tissue was significantly improved ；SUA content ，XOD activity in serum and liver tissue ，the relative mRNA and protein expression of XOD in liver tissue ，and the relative expression of URAT 1 protein in renal tissue were decreased significantly in administration groups （P＜0.05）. The relative expression of GLUT 9 protein in renal tissue of mice in benzbromarone group and ECS high-dose group decreased significantly （P＜0.05）；relative expression of OAT 1 protein in renal tissue of mice in benzbromarone group ，WCS low-dose and high-dose groups ，ECS low-dose group were increased significantly （P＜0.05）. CONCLUSIONS WCS and ECS can significantly decrease the contents of SUA in HUA model mice ，and improve pathological state of renal tissue ，the mechanism of which may be associated with inhibiting XOD activity and uric acid reabsorption，and down-regulating protein and mRNA expression of XOD.
RESUMO
OBJECTIVE：To study in vi tro inhibitory act ivities of 9 kinds of TCM for dredging collaterals and dispelling wind on xanthine oxidase （XO），and to screen TCM with outstanding activity. METHODS ：Using xanthine as substrate and xanthinase as reaction enzyme ，allopurinol as positive control ，with water extract and methanol extract （hereinafter referred to as “ethanol extract”）from the stem and leaves of Hedera nepalensis ，the whole plant of Piper wallichii ，the fruits of Rubus corchorifolius ，the root of Caragana sinica ，the root of Wisteria sinensis ，the root of Rubus crataegifolius ，the bark of Catalpa ovata ，the root of Campsis grandiflora ，the stem of P. hancei （hereinafter referred to by plant name ）and petroleum ether ，dichloromethane，ethyl acetate，n-butanol and water fraction of active extract as the objects ，inhibition rate of each sample to XO was detected by spectrophotometry；IC50values were calculated with Graphpad prism 6.0 software to screen active extract/fraction. Double reciprocal method was used to determine the type of enzyme inhibition. RESULTS ：Among 9 kinds of TCM and 18 kinds of the extracts ，the inhibitory rates to XO of 500 μg/mL extracts from each TCM（except for ethanol extract of P. wallichii ），250 μg/mL water extract and ethanol extract of H. nepalensis ，P. wallichii ，R. corchorifolius and P. hancei ，250 μg/mL water extract of C. ovata ，250 μ g/mL ethanol extract of C. sinica ，R. crataegifolius and C. grandiflora ，125 μ g/mL ethanol extract of C. sinica and R. crataegifolius，62.5 μg/mL ethanol extract of C. sinica were more than 50％. The IC 50 value of the ethanol extract from C. sinica was 43.43 μg/mL，which was lower than the extracts of other TCM ，and which was the active extract. The IC 50 values of petroleum ether，dichloromethane，ethyl acetate ，n-butanol and water fracti on of ethanol extract from C. sinica were ＞200，193.35，7.67， 14.80 and ＞200 μg/mL，respectively. The IC 50 value of ethyl XO was competitive-noncompetitive inhibition ， which was different from competi tive inhibition of positive control. CONCLUSIONS：The ethanol extracts of C. sinica ，R. crataegifolius ，P. wallichii ，R. corchorifolius ，P. hancei ，H. nepalensis and the water extracts of H. nepalensis ，P. wallichii ，C. ovata show certain inhibitory activity in vitro to XO ，especially ethanol extract of C. sinica . The ethyl acetate fraction of the ethanol extract of C. sinica has similar inhibitory activity to allopurinol but their inhibition types are different.