In Vitro Inhibitory Effect of Licoricidin on Human Cytochrome P450s

IF 0.4 Q4 SPECTROSCOPY

Mass Spectrometry Letters Pub Date : 2014-09-30 DOI:10.5478/MSL.2014.5.3.84

Sun Ju Kim, O. Heungchan, Jeong Ah Kim, Seung Ho Lee, Sangkyu Lee

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引用次数: 2

Abstract

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at with CYP probes for 60 min at , it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4`-hydroxylation with half maximal inhibitory concentration () values of 3.4 and , respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with values of 4.5 and , respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

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甘草苷对人细胞色素p450的体外抑制作用

从甘草中分离得到的Licoricidin具有抗癌、抗肾病、抗幽门螺杆菌和抗菌作用。本研究采用鸡尾酒探针法和液相色谱-串联质谱法(LC-MS/MS)研究了甘草苷对人肝微粒体细胞色素P450 (CYP)酶的调节作用。甘草霉素与CYP探针孵育60 min后，对cyp2b6催化的安非他酮羟基化和cyp2c9催化的双氯芬酸4′-羟基化表现出较强的抑制作用，最大抑制浓度()值分别为3.4和一半。licoricidin的抑制模式为竞争性、剂量依赖性和非时间依赖性，符合Lineweaver-Burk图。甘草霉素对人重组cdna表达的CYP2B6和2C9的抑制作用已被证实，分别为4.5和2C9。总之，本研究表明，甘草霉素对CYP2B6和CYP2C9活性的有效抑制作用，可能对预测草药与主要由CYP2B-和CYP2C9介导代谢的底物的潜在相互作用具有重要意义。

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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