Rui Wang, Kai Zheng, Yunjiao Liu, Shuxia Ji, Yaxin Tang, Jie Wang, Rong Jiang
{"title":"tubeimoside I 对人肝脏微粒体中细胞色素 P450 酶活性的影响。","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":"<p><p>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 IC<sub>50</sub> values of 10.34, 11.58, and 9.74 μM, respectively. The inhibition of CYP2D6 and 2E1 was competitive with the <i>K<sub>i</sub></i> value of 5.66 and 5.29 μM, respectively. While the inhibition of CYP3A4 was non-competitive with the <i>K<sub>i</sub></i> value of 4.87 μM. Moreover, the inhibition of CYP3A4 was time-dependent with the <i>K<sub>I</sub></i> and <i>K</i><sub>inact</sub> values of 0.635 μM<sup>-1</sup> and 0.0373 min<sup>-1</sup>, 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.</p>","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":"{\"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\":\"<p><p>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 IC<sub>50</sub> values of 10.34, 11.58, and 9.74 μM, respectively. The inhibition of CYP2D6 and 2E1 was competitive with the <i>K<sub>i</sub></i> value of 5.66 and 5.29 μM, respectively. While the inhibition of CYP3A4 was non-competitive with the <i>K<sub>i</sub></i> value of 4.87 μM. Moreover, the inhibition of CYP3A4 was time-dependent with the <i>K<sub>I</sub></i> and <i>K</i><sub>inact</sub> values of 0.635 μM<sup>-1</sup> and 0.0373 min<sup>-1</sup>, 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.</p>\",\"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}","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}
Effect of tubeimoside I on the activity of cytochrome P450 enzymes in human liver microsomes.
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.
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
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