桑叶提取物对大鼠体内细胞色素P450酶活性的影响

目的 采用“Cocktail”混合探针药物法，探究桑叶水提物（aqueous extract of mulberry leaves，AML）、桑叶醇提物（ethanol extract of mulberry leaves，EML）对大鼠体内细胞色素P450（cytochrome P450,CYP450）酶活性的影响，从代谢酶的角度预测它可能引起的药物相互作用，为临床合理用药提供参考。方法 选用非那西丁、安非他酮、双氯酚酸钠作为大鼠体内3种CYP450酶（CYP1A2、CYP2B6、CYP2C9）的探针药物。雄性SD大鼠连续灌胃桑叶提取物14 d，第14天灌胃后30 min尾静脉注射混合探针药物，根据不同时间点采血。采用超高效液相色谱- 串联质谱测定各组血药浓度，用DAS 2.0和SPSS 21.0软件拟合药物代谢动力学参数并进行统计学分析。结果 连续灌胃桑叶提取物14 d后，与9.0 g/L氯化钠注射液相比，AML组中非那西丁、双氯酚酸钠代谢减慢，安非他酮则不明显；与羧甲基纤维素钠组相比，EML组中安非他酮、双氯酚酸钠代谢减慢，非那西丁则不明显。结论 AML对大鼠体内CYP1A2、CYP2C9可能存在一定的抑制作用，对CYP2B6可能无显著性影响；EML对大鼠体内CYP2B6、CYP2C9可能存在一定的抑制作用，对CYP1A2可能无显著性影响。

Effect of Mulberry Leaf Extract on the Activity of Cytochrome P450 Enzymes in Rats

Objective To investigate the effects of aqueous extract of mulberry leaves (AML) and ethanol extract of mulberry leaves (EML) on the activity of cytochrome P450 enzymes in rats based on the cocktail probe drug method, as well as possible drug interactions caused by AML and EML from the aspect of metabolic enzymes, and to provide a reference for rational drug use in clinical practice. Methods Phenacetin, bupropion, and diclofenac sodium were selected as the probe drugs for three cytochrome P450 enzymes in rats (CYP1A2, CYP2B6, and CYP2C9). Male Sprague- Dawley rats were given mulberry leaf extract by gavage for 14 consecutive days, and tail vein injection of probe drugs was performed at 30 minutes after the last administration on day 14. Blood samples were collected at different time points. Liquid chromatography- tandem mass spectrometry was used to measure the plasma concentrations of drugs, and DAS 2.0 and SPSS 21.0 were used for the fitting of pharmacokinetic parameters and were used to perform a statistical analysis. Results Compared with the 9.0 g/L sodium chloride injection group, the AML group had significant reductions in the metabolic rates of phenacetin and diclofenac sodium after 14 consecutive days of intragastric administration of AML, while there was no significant change in the metabolic rate of bupropion. Compared with the sodium carboxymethyl cellulose group, the EML group had significant reductions in the metabolic rates of bupropion and diclofenac sodium, while there was no significant change in the metabolic rate of phenacetin. Conclusion AML may have a certain inhibitory effect on the activities of CYP1A2 and CYP2C9 in rats, and may have no marked influence on the activity of CYP2B6. EML may have a certain inhibitory effect on the activities of CYP2B6 and CYP2C9 in rats, and may have no marked influence on the activity of CYP1A2.