朝藿定用于药物-草药相互作用的潜力。

The potential of Epimedium koreanum Nakai for herb-drug interaction.

机构信息

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, China.

出版信息

J Pharm Pharmacol. 2017 Oct;69(10):1398-1408. doi: 10.1111/jphp.12773. Epub 2017 Jun 27.

DOI:10.1111/jphp.12773

PMID:28653752

Abstract

OBJECTIVES

This study aims to investigate potential herb-drug interactions (HDI) of Epimedium koreanum Nakai.

METHODS

Human liver microsomes (HLMs) were used to determine the enzyme kinetics of the major human cytochrome P450s (CYPs). Inducible potential of E. koreanum on CYP1A2, 2B6, 2C19 and 3A4 activities of human primary hepatocytes was also examined.

KEY FINDINGS

Ethanol extract of E. koreanum showed direct inhibitory potency for CYP1A2 (IC = 121.8 μg/ml, K = 110.7 ± 36.8 μg/ml) and CYP2B6 (IC = 59.5 μg/ml, K = 18.1 ± 2.9 μg/ml). For CYP2C9, 2C19, 2D6, 2E1 and 3A4, only negligible effect was observed. Time-dependent (irreversible) inhibition by E. koreanum was observed for CYP1A2 (K = 32.9 ± 18.4 μg/ml, k = 0.031 ± 0.006 min ). However, ethanol extract of E. koreanum (1.5-150 μg/ml) did not change the activity or mRNA expressions for CYP3A4, 1A2, 2C19 and 2B6.

CONCLUSIONS

The ethanol extract of E. koreanum is not likely to cause HDI via inducing the major human CYPs. But the potential for interactions between E. koreanum extract and substrates of CYP1A2 or 2B6 cannot be overlooked.

摘要

目的

本研究旨在探讨朝藿定 C 与药物相互作用的潜在风险。

方法

用人肝微粒体（HLMs）测定主要人细胞色素 P450s（CYPs）的酶动力学。还检测了朝藿定 C 对人原代肝细胞 CYP1A2、2B6、2C19 和 3A4 活性的诱导潜力。

主要发现

朝藿定 C 的乙醇提取物对 CYP1A2（IC = 121.8 μg/ml，K = 110.7 ± 36.8 μg/ml）和 CYP2B6（IC = 59.5 μg/ml，K = 18.1 ± 2.9 μg/ml）具有直接抑制作用。对于 CYP2C9、2C19、2D6、2E1 和 3A4，仅观察到可忽略的作用。朝藿定 C 表现出时间依赖性（不可逆）抑制 CYP1A2（K = 32.9 ± 18.4 μg/ml，k = 0.031 ± 0.006 min ）。然而，朝藿定 C 的乙醇提取物（1.5-150 μg/ml）并未改变 CYP3A4、1A2、2C19 和 2B6 的活性或 mRNA 表达。