采用 UPLC-MS/MS 法用鸡尾酒探针法评价左归丸对大鼠 6 种 CYP450 同工酶的影响。
Evaluation of Zuo-Gui Yin Decoction Effects on Six CYP450 Enzymes in Rats Using a Cocktail Method by UPLC-MS/MS.
机构信息
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, China.
Institute of Drug Metabolism, Anhui University of Chinese Medicine, Hefei, Anhui, China.
出版信息
Biomed Res Int. 2022 Aug 26;2022:4293062. doi: 10.1155/2022/4293062. eCollection 2022.
BACKGROUND
Zuo-Gui Yin Decoction (ZGYD), a traditional Chinese prescription, is mainly used in various kinds of andrology and gynecology diseases. However, the study on the interaction of ZGYD and drugs has not been reported. Therefore, evaluating the interaction between ZGYD and metabolic enzymes is helpful to guide rational drug use.
OBJECTIVE
This study was conducted to explore the effects of ZGYD on the activity and mRNA expressions of six Cytochrome P450 (CYP450) enzymes in rats and to provide a basis for its rational clinical use.
METHODS
Sprague-Dawley rats were randomly divided into control, ZGYD high, medium, and low-dose group ( = 6). The concentrations of six probe substrates in plasma of rats in each group were determined by UPLC-MS/MS. In addition, RT-PCR and Western blot were used to determine the effects of ZGYD on the expression of CYP450 isoforms in the liver.
RESULTS
Compared with the control group, the main pharmacokinetic parameters AUC, AUC , of omeprazole, dextromethorphan, and midazolam in the high-dose group were significantly decreased, while the CL of these were significantly increased. The gene expressions of CYP2C11 and CYP3A1 were upregulated in the ZGYD medium, high-dose group. The protein expression of CYP2C11 was upregulated in the high-dose group, and the protein expression of CYP3A1 was upregulated in the medium, high-dose group.
CONCLUSION
The results showed that ZGYD exhibited the induction effects on CYP2C11 and CYP3A1 (CYP2C19 and CYP3A4 in humans) in rats. However, no significant change in CYP1A2, CYP2B1, CYP2C7, and CYP2D2 activities was observed. It would be useful for the safe and effective usage of ZGYD in clinic.
背景
左归丸（ZGYD）是一种传统的中药方剂，主要用于治疗各种男科和妇科疾病。然而，关于 ZGYD 与药物相互作用的研究尚未报道。因此，评估 ZGYD 与代谢酶的相互作用有助于指导合理用药。
目的
本研究旨在探讨 ZGYD 对大鼠 6 种细胞色素 P450（CYP450）酶活性和 mRNA 表达的影响，为其合理临床应用提供依据。
方法
将 Sprague-Dawley 大鼠随机分为对照组、ZGYD 高、中、低剂量组（每组 6 只）。采用 UPLC-MS/MS 法测定各组大鼠血浆中 6 种探针底物的浓度。此外，采用 RT-PCR 和 Western blot 法测定 ZGYD 对肝脏 CYP450 同工酶表达的影响。
结果
与对照组相比，高剂量组奥美拉唑、右美沙芬和咪达唑仑的主要药代动力学参数 AUC、AUC 显著降低，而 CL 显著增加。ZGYD 中、高剂量组 CYP2C11 和 CYP3A1 的基因表达上调。高剂量组 CYP2C11 蛋白表达上调，中、高剂量组 CYP3A1 蛋白表达上调。
结论
结果表明，ZGYD 对大鼠 CYP2C11 和 CYP3A1（人类 CYP2C19 和 CYP3A4）表现出诱导作用。然而，CYP1A2、CYP2B1、CYP2C7 和 CYP2D2 的活性没有明显变化。这对于 ZGYD 在临床中的安全有效使用将是有用的。
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