An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2.

IF 2.6 3区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY
Chung-Ping Yu, Pei-Ying Li, Szu-Yu Chen, Shiuan-Pey Lin, Ying-Chen Chen, Lu-Ching Ho, Yow-Wen Hsieh, Yu-Chi Hou
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Abstract

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

厚朴通过抑制多药耐药性相关蛋白 2 与甲氨蝶呤产生急性草药-药物相互作用。
厚朴(MOC)是一种中药,含有多酚木脂素,主要是厚朴酚(MN)和厚朴酚(HK)。甲氨蝶呤(MTX)是治疗癌症和自身免疫性疾病的重要药物,是多药耐药性相关蛋白 2(MRP2)和乳腺癌耐药性蛋白(BCRP)的底物。本研究探讨了联合给药 MOC 对 MTX 药代动力学的影响及其相关机制。研究人员给 Sprague-Dawley 大鼠口服单剂量(2.0 克/千克和 4.0 克/千克)MTX 和重复 7 次剂量的 MOC(2.0 克/千克,每天 3 次,共 2 天,第 7 次剂量在 MTX 给药前 0.5 小时给药)。通过荧光偏振免疫测定法测定血清中的 MTX 浓度。结果显示,单次服用 2.0 克/千克的 MOC 可使 MTX 的 AUC0-t 和 MRT 分别显著提高 352% 和 308%,单次服用 4.0 克/千克的 MOC 可使 MTX 的 AUC0-t 和 MRT 分别显著提高 362% 和 291%。同样,重复服用七次 2.0 克/千克剂量的 MOC 可使 MTX 的 AUC0-t 和 MRT 分别显著提高 461% 和 334%。机理研究表明,MN、HK 和 MOC 的血清代谢物(MOCM)会明显抑制 MRP2 的功能,而 MOCM 不会抑制 BCRP。总之,通过抑制MRP2介导的MTX排泄,联合给药MOC可明显增加MTX的全身暴露量和平均停留时间。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Food and Drug Analysis
Journal of Food and Drug Analysis 医学-食品科技
CiteScore
6.30
自引率
2.80%
发文量
36
审稿时长
3.8 months
期刊介绍: The journal aims to provide an international platform for scientists, researchers and academicians to promote, share and discuss new findings, current issues, and developments in the different areas of food and drug analysis. The scope of the Journal includes analytical methodologies and biological activities in relation to food, drugs, cosmetics and traditional Chinese medicine, as well as related disciplines of topical interest to public health professionals.
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