[Effect of Clopidogrel on Plasma Protein Binding Rates of Ginsenoside Rg1].

中国中西医结合杂志 Pub Date : 2017-04-01
Ma Shi-Tang, Guo-Liang Dal, Xiao-Gui Cheng, Wen-Zhu Zhao, Bing-Ting Sun, Wen-Zheng Ju, Heng-Shan Tan
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Abstract

Objective To observe the effect of clopidogrel on plasma protein binding rates of gin- senoside Rg1. Methods Concentrations of ginsenoside Rg1 were measured in fetal bovine serum and phosphate buffered solution (PBS). Samples were randomly divided into ginsenoside Rg1 groups (low: 0.4; middle: 1. 0; high 5. 0 mg/L, respectively) and clopidogrel combined ginsenoside Rg1 groups (low: 0. 4 mg/L +2. 0 mg/L clopidogrel; middle: 1. 0 mg/L +2. 0 mg/L clopidogrel; high: 5. 0 mg/L +2. 0 mg/L clo- pidogrel). The effect of clopidogrel on plasma protein binding rates of ginsenoside Rgl was observed u- sing equilibrium dialysis. Then 3-dimensional structure of bovine serum albumin (BSA) was constructed using homology modeling. On this basis, binding effect of small compounds (ginsenoside Rg1 and clopi- dogrel) and BSA was observed using molecular docking method. Results The serum protein binding rate was 11. 2% ±2. 1% in the low dose ginsenoside Rg1 group, 13. 4% ±2. 2% in the middle dose ginsenoside Rgl group, and 14. 6% ±1. 4% in the high dose ginsenoside Rg1 group, respectively. It was 6. 5% ±2. 3% in the clopidogrel combined low dose ginsenoside Rg1 group, 9. 2% ±1. 5% in the clopi- dogrel combined middle dose ginsenoside Rg1 group, 12.1% ± 1. 7% in the clopidogrel combined high dose ginsenoside Rg1 group, respectively. They were lower in clopidogrel combined ginsenoside Rg1 groups than in ginsenoside Rg1 groups with statistical difference (P <0. 05). Results of molecular doc- king showed that competitive binding effect existed between compounds (ginsenoside Rg1 and clopi- dogrel) and BSA. Conclusion Results of equilibrium dialysis and molecular docking comprehensively in- dicated clopidogrel had effect on plasma protein binding rate of ginsenoside Rg1.

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氯吡格雷对人参皂苷Rg1血浆蛋白结合率的影响
目的观察氯吡格雷对银杏皂苷Rg1血浆蛋白结合率的影响。方法测定胎牛血清和磷酸缓冲液(PBS)中人参皂苷Rg1的浓度。样品随机分为人参皂苷Rg1组(低:0.4;中:1。0;高5。0 mg/L)和氯吡格雷联合人参皂苷Rg1组(低:0。4mg /L +2。氯吡格雷0 mg/L;中:1。0 mg/L +2。氯吡格雷0 mg/L;高:5。0 mg/L +2。0 mg/L氯吡格雷)。通过平衡透析观察氯吡格雷对血浆人参皂苷Rgl蛋白结合率的影响。利用同源性模型构建了牛血清白蛋白(BSA)的三维结构。在此基础上,采用分子对接法观察小分子化合物(人参皂苷Rg1和clopi- dogrel)与牛血清白蛋白的结合作用。结果血清蛋白结合率为11%。2%±2。1 .低剂量人参皂苷Rg1组;4%±2。中剂量人参皂苷Rgl组2%;6%±1。高剂量人参皂苷Rg1组分别为4%。是6。5%±2。3 .氯吡格雷联合低剂量人参皂苷Rg1组;2%±1。克罗比-狗格雷联合中剂量人参皂苷Rg1组5%,12.1%±1。氯吡格雷联合大剂量人参皂苷Rg1组分别为7%。氯吡格雷联合人参皂苷Rg1组低于人参皂苷Rg1组,差异有统计学意义(P
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