摘要
目的研究无梗五加果实提取物对大鼠CYP450亚型CYP1A2、CYP2C19、CYP2E1、CYP3A4活性的影响。方法以咖啡因、奥美拉唑、氯唑沙宗和咪达唑仑作为CYP1A2、CYP2C19、CYP2E1和CYP3A4特异性探针药物,配制cocktail混合探针溶液,建立同时测定4种探针药物血药浓度的高效液相色谱法。将SD大鼠随机分为无梗五加果实70%乙醇提取物组、水提取物组和对照组,每天分别ig无梗五加果实70%乙醇提取物溶液、水提取物溶液和溶剂10 mL/kg,连续给药1周,于第8天ip混合探针药物10 mL/kg,分别在给药0、0.083、0.25、0.417、0.583、0.833、1、2、3、5、8、11、12 h于大鼠眼眶静脉丛采血,采用HPLC法对血浆样品进行分析,对给药组和对照组探针药物的药动学参数生物半衰期(t_(1/2))进行比较。结果与对照组比较,无梗五加果实水提取物组和70%乙醇提取物组咖啡因、咪达唑仑的t_(1/2)显著降低,奥美拉唑、氯唑沙宗的t_(1/2)显著增加,差异均具有统计学意义(P<0.05、0.01)。结论无梗五加果实70%乙醇提取物和水提取物对大鼠的CYP2C19、CYP2E1有抑制作用,对大鼠的CYP1A2、CYP3A4有诱导作用。
Objective： Objective To study effects of Acanthopanax sessiliflorus fruit extract on four isoforms of CYP1A2, CYP2C19, CYP2E1, and CYP3A4 activities of CYP450 of rats. Methods Using caffine, omeprazole, chlorzaxazone, and midazolam as the specific probe drugs to make the cocktail probe solution for CYP1A2, CYP2C19, CYP2E1, and CYP3A4, respectively. An HPLC method was established to simultaneously determinate the concentrate of four probe drugs in plasma. Rats were randomly divided into two medicine groups and a control group. They were administrated of 70% ethanol and water extracts of A. sessiliflorus fruit and blank solvent 10 mL/kg for one week. And then they were injected the cocktail solution by abdominal cavity at the eighth day, the blood samples were obtained through the eyeballs extirpating at a series of time-points 0, 0.083, 0.25, 0.417, 0.583, 0.833, 1, 2, 3, 5, 8, 11, and 12 h. The plasma samples were analyzed by HPLC method. The pharmacokinetic parameters half-life （t1/2） of the probe drugs were compared between the control group and medicine groups. Results Compared with the control group, t1/2 of caffeine and midazolam in A. sessiliflorus fruit extract water and 70% ethanol extracts groups were notablely shorten, while omeprazole and chlorzoxazone were prominently prolonged, with significant difference between two groups （P 〈 0.05, 0.01）. Conclusion The activities of A. sessiliflorus fruit extract water and 70% ethanol extracts on CYP1A2 and CYP3A4 of rats are induced, but on CYP2C29 and CYP2E1 of rats are inhibited.
出处
《现代药物与临床》
CAS
2017年第8期1410-1415,共6页
Drugs & Clinic
基金
辽宁省自然科学基金资助项目(20102147
辽宁中医药大学优秀青年药学人才基金项目(yxrc0902)
