The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
J Ethnopharmacol. 2014 Feb 12;151(3):1141-1146. doi: 10.1016/j.jep.2013.12.025. Epub 2013 Dec 27.
In traditional therapy with Chinese medicine, hydroxysafflor yellow A (HSYA), a main active component isolated from the dried flower of Carthamus tinctorius L., is the principal efficiency ingredient of Safflor Yellow Injection. Now HSYA has been demonstrated to have good pharmacological activities of antioxidation, myocardial and cerebral protective and neuroprotective effects. The purpose of this study was to find out whether HSYA influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, CYP2D4 and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied.
A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), tolbutamide (5 mg/kg), dextromethorphan (20 mg/kg) and midazolam (10 mg/kg), was given as oral administration to rats treated with short or long period of intravenous HSYA via the caudal vein. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time RT-PCR was performed to determine the effect of HSYA on the mRNA expression of CYP1A2, CYP2C11, CYP2D4 and CYP3A1 in rat liver.
HSYA had significant inhibition effects on CYP1A2 and CYP2C11 in rats as oriented from the pharmacokinetic profiles of the probe drugs. Furthermore, HSYA had no effects on rat CYP2D4. However, CYP3A1 enzyme activity was induced by HSYA. The mRNA expression results were in accordance with the pharmacokinetic results.
HSYA can either inhibit or induce activities of CYP1A2, CYP2C11 and CYP3A1. Therefore, co-administration of some CYP substrates with HSYA may need dose adjustment to avoid an undesirable herb-drug interaction.
在传统的中药治疗中，红花黄色素 A（HSYA）是红花的主要活性成分之一，是红花黄色素注射液的主要有效成分。现已证实，HSYA 具有良好的抗氧化、心肌和脑保护及神经保护作用。本研究旨在探讨 HSYA 是否通过体内鸡尾酒探针药物影响大鼠细胞色素 P450（CYP）酶（CYP1A2、CYP2C11、CYP2D4 和 CYP3A1）的作用，同时研究其对 CYP mRNA 水平的影响。
尾静脉注射给予大鼠短期或长期 HSYA 后，给予 5mL/kg 的鸡尾酒溶液（含 20mg/kg 的非那西汀、5mg/kg 的甲苯磺丁脲、20mg/kg 的右美沙芬和 10mg/kg 的咪达唑仑）。在一系列时间点采集血样，采用 HPLC-MS/MS 测定血浆中探针药物的浓度。采用 DAS 2.0 软件计算相应的药代动力学参数。此外，采用实时 RT-PCR 法测定 HSYA 对大鼠肝 CYP1A2、CYP2C11、CYP2D4 和 CYP3A1 基因表达的影响。
从探针药物的药代动力学特征来看，HSYA 对 CYP1A2 和 CYP2C11 有明显的抑制作用。此外，HSYA 对大鼠 CYP2D4 无影响，但 CYP3A1 酶活性被 HSYA 诱导。mRNA 表达结果与药代动力学结果一致。
HSYA 可抑制或诱导 CYP1A2、CYP2C11 和 CYP3A1 的活性。因此，与 HSYA 联合使用某些 CYP 底物时，可能需要调整剂量，以避免不良的草药-药物相互作用。
