Effect of tubeimoside I on the activity of cytochrome P450 enzymes in human liver microsomes.

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2024-02-01 Epub Date: 2024-01-12 DOI:10.1080/00498254.2023.2301352

Rui Wang, Kai Zheng, Yunjiao Liu, Shuxia Ji, Yaxin Tang, Jie Wang, Rong Jiang

{"title":"Effect of tubeimoside I on the activity of cytochrome P450 enzymes in human liver microsomes.","authors":"Rui Wang, Kai Zheng, Yunjiao Liu, Shuxia Ji, Yaxin Tang, Jie Wang, Rong Jiang","doi":"10.1080/00498254.2023.2301352","DOIUrl":null,"url":null,"abstract":"This study assessed the effect of tubeimoside I on CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 to reveal the potential of tubeimoside I to induce drug-drug interaction.The evaluation of cytochromes P450 enzyme (CYP) activity was performed in pooled human liver microsomes with probing substrates of CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Typical inhibitors were employed as positive controls and the effect of 0, 2.5, 5, 10, 25, 50, and 100 μM tubeimoside I was investigated.The activity of CYP2D6, 2E1, and 3A4 was significantly inhibited by tubeimoside I with the IC50 values of 10.34, 11.58, and 9.74 μM, respectively. The inhibition of CYP2D6 and 2E1 was competitive with the Ki value of 5.66 and 5.29 μM, respectively. While the inhibition of CYP3A4 was non-competitive with the Ki value of 4.87 μM. Moreover, the inhibition of CYP3A4 was time-dependent with the KI and Kinact values of 0.635 μM-1 and 0.0373 min-1, respectively.Tubeimoside I served as a competitive inhibitor of CYP2D6 and 2E1 exerting weak inhibition and a non-competitive inhibitor of CYP3A4 exerting moderate inhibition.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"57-63"},"PeriodicalIF":1.3000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Xenobiotica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00498254.2023.2301352","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/12 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

This study assessed the effect of tubeimoside I on CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 to reveal the potential of tubeimoside I to induce drug-drug interaction.The evaluation of cytochromes P450 enzyme (CYP) activity was performed in pooled human liver microsomes with probing substrates of CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Typical inhibitors were employed as positive controls and the effect of 0, 2.5, 5, 10, 25, 50, and 100 μM tubeimoside I was investigated.The activity of CYP2D6, 2E1, and 3A4 was significantly inhibited by tubeimoside I with the IC₅₀ values of 10.34, 11.58, and 9.74 μM, respectively. The inhibition of CYP2D6 and 2E1 was competitive with the K_i value of 5.66 and 5.29 μM, respectively. While the inhibition of CYP3A4 was non-competitive with the K_i value of 4.87 μM. Moreover, the inhibition of CYP3A4 was time-dependent with the K_I and K_inact values of 0.635 μM^-1 and 0.0373 min^-1, respectively.Tubeimoside I served as a competitive inhibitor of CYP2D6 and 2E1 exerting weak inhibition and a non-competitive inhibitor of CYP3A4 exerting moderate inhibition.

查看原文本刊更多论文

tubeimoside I 对人肝脏微粒体中细胞色素 P450 酶活性的影响。

本研究评估了管果苷 I 对 CYP1A2、2A6、2C8、2C9、2C19、2D6、2E1 和 3A4 的影响，以揭示管果苷 I 诱导药物相互作用的可能性。利用 CYP1A2、2A6、2C8、2C9、2C19、2D6、2E1 和 3A4 的探查底物，在汇集的人类肝脏微粒体中评估了细胞色素 P450 酶（CYP450）的活性。典型的抑制剂被用作阳性对照，0、2.5、5、10、25、50 和 100 μM 的管胞苷 I 均对 CYP2D6、2E1 和 3A4 的活性有显著的抑制作用，IC50 值分别为 10.34、11.58 和 9.74 μM。对 CYP2D6 和 2E1 的抑制是竞争性的，Ki 值分别为 5.66 和 5.29 μM。对 CYP3A4 的抑制是非竞争性的，Ki 值为 4.87 μM。此外，对 CYP3A4 的抑制作用与时间有关，KI 和 Kinact 值分别为 0.635 μM-1 和 0.0373 min-1。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology