Protective Effect of Polydatin Complicated with Emodin on Hyperuricemia Model Rats with Median Effect Principle / 中国药房

ABSTRACT

OBJECTIVE：To s tudy the protective effect of polydat in complicated with emodin on hyperuricemia （HUA）model rats，and to screen the optimal complication proportion and investigate the potential mechanism. METHODS ：SD rats were randomly divided into normal control group ，model group ，benzbromarone group （positive control ，8 mg/kg），polydatin alone group，emodin alone group and drug combination group A ，B，C，with 5 rats in each group of each dosage. Normal control group and model group were given constant volume of 0.3％ CMC-Na solution ，administration groups were given relevant medicine intragastrically. Each group was given 0.1 mL/10 g intragastrically once a day ，for consecutive 7 d. Expect for normal control group，other groups were given intraperitoneal injection of potassium oxonate 300 mg/kg 1 h before last medication to induce HUA model. One hour after last medication ，the serum contents of uric acid （UA）were determined in normal control group ，model group，benzbromarone group ，polydatin/alone group （0.625，1.25，2.5，5，10 mg/kg）and drug combination group A [the dose of polydatin+emodin were （0.625+0.625），（1.25+1.25），（2.5+ 2.5），（5 + 5），（10 + 10） mg/kg]. The effect （Fa） and combination index （CI） of above single drug groups and combination groups were calculated by the median effect principle. The dose-effect relationship curves of twocomponents alone or combination were drawn ；Fa-CI curves after simulation were als o drawn to evaluate the effect of two-drug combination. Serum contents of UA in rats were determined and Fa value was calculated in single drug groups and drug combination group B ，C [the dose of polydatin+emodin were （0.625+ 0.625），（0.625+1.25），（0.625+2.5），（0.625+5），（0.625+10）mg/kg and （0.625+0.625），（1.25+0.625），（2.5+0.625），（5+ 0.625），（10+0.625）mg/kg]. The optimal complication proportion of two drugs were screened. The serum contents of xanthine oxidase（XOD）in rats were determined in normal control group ，model group ，benzbromarone group ，polydatin/emodin alone group（10 mg/kg）and the optimal complication proportion groups. The mechanism was analyzed primarily. RESULTS ：Compared with normal control group ，the content of UA in model group was increased significantly （P＜0.01）. Compared with model group ， except for 0.625 mg/kg polydatin alone group ，the content of UA in other administration groups were decreased significantly （P＜ 0.05 or P＜0.01）. When the two drugs were used alone or in combination ，Fa value was positively correlated with drug dose （intercept＞0，correlation coefficient ＞0.9），and Fa value of the combination group was higher than that of any single drug group ； when the simulated Fa value was more than 15％，the corresponding CI value was less than 1，two-drug combination showed synergistic effect. When the complication proportion of polydatin and emodin was 1∶4，the Fa value （53.10）was similar to that of drug combination group A （53.73），and the dose of them were less [ （0.625+2.5）mg/（kg·d）vs.（2.5+2.5）mg/（kg·d）]. Compared with normal control group ，serum content of XOD in model group was increased significantly （P＜0.01）；compared with model group，serum content of XOD in administration groups were decreased significantly ，and the optimal complication proportion group was significantly lower than polydatin alone group and emodin alone group （P＜0.05 or P＜0.01）. CONCLUSIONS ：The polydatin and emodin used alone or in combination can reduce the serum content of UA in HUA model rats by inhibiting the generation of XOD. They have a certain synergistic effect ，and the optimal complication proportion is 1∶4.