He Fan, Jiang Ting, Hong Shizhong, Wang Lei, Chen Weidong, Liu Li
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, China.
Institute of Drug Metabolism, Anhui University of Chinese Medicine, Hefei, Anhui, China.
Evid Based Complement Alternat Med. 2020 May 13;2020:9784946. doi: 10.1155/2020/9784946. eCollection 2020.
You-Gui Yin (YGY) is a traditional Chinese medicine (TCM) decoction composed of eight Chinese herbs. The interaction between TCM and Western medicine has attracted much attention nowadays. It is therefore necessary to study the clinical application of YGY in combination with Western medicine from the perspective of metabolic enzymes. This study aims to investigate the effect of YGY on the activities of seven CYP450 isozymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) in rats. Twenty-four Sprague-Dawley (SD) rats were randomly divided into four groups: high, middle, and low-dose YGY-treated groups and the control group. They were given 13.78, 20.67, and 31 g/kg/d YGY decoction by oral administration and normal saline (10 mL/kg), respectively, for 14 days. Half an hour after the last administration, a mixed probe substrate (1 mg/kg) was administered by tail vein injection. Then, blood was taken from the venous plexus at different time points. The protein expression level of the CYP450 enzymes in the control and treatment groups was determined by western blot. The effect of YGY on the activity of CYP isoenzymes was studied by comparing the plasma pharmacokinetics between the control and treatment groups. Compared with the control group, YGY at a high (31 g/kg) dosage could decrease AUC, AUC and of diclofenac, omeprazole, and midazolam by at least 35.4%, while increase CL by at least 88.9%; this revealed that YGY could induce CYP2C9, CYP2C19, and CYP3A4. The results show that when we use You-Gui Yin decoction in combination with other drugs, especially drugs metabolized by CYP2C9, CYP2C19, and CYP3A4 enzymes, the interaction between drugs needs special attention.
右归丸(YGY)是一种由八味中药组成的中药汤剂。如今,中西医结合受到了广泛关注。因此,有必要从代谢酶的角度研究右归丸与西药联合应用的临床情况。本研究旨在探讨右归丸对大鼠七种细胞色素P450同工酶(CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6和CYP3A4)活性的影响。将24只Sprague-Dawley(SD)大鼠随机分为四组:高、中、低剂量右归丸治疗组和对照组。分别给予大鼠13.78、20.67和31 g/kg/d的右归丸汤剂及生理盐水(10 mL/kg),连续给药14天。末次给药半小时后,尾静脉注射混合探针底物(1 mg/kg)。然后,在不同时间点从静脉丛取血。通过蛋白质免疫印迹法测定对照组和治疗组中细胞色素P450酶的蛋白表达水平。通过比较对照组和治疗组的血浆药代动力学,研究右归丸对细胞色素P450同工酶活性的影响。与对照组相比,高剂量(31 g/kg)的右归丸可使双氯芬酸、奥美拉唑和咪达唑仑的AUC、AUC和Cmax至少降低35.4%,而使CL至少增加88.9%;这表明右归丸可诱导CYP2C9、CYP2C19和CYP3A4。结果表明,当右归丸汤剂与其他药物联合使用时,尤其是与经CYP2C9、CYP2C19和CYP3A4酶代谢的药物合用时,需要特别关注药物之间的相互作用。