In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes

Context: Kaempferitrinis (KF) is a bioactive flavonoid and possesses numerous pharmacological activities. However, whether KF affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the effects of KF on eight major CYP isoforms in human l...

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Autores principales:	Ning Zhang, Jing Liu, Zhixia Chen, Wenwen Dou
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	cyp1a2 cyp3a4 cyp2c9 herb-drug interaction Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/cbf32919af56482c87b0f4f7be9aea63
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spelling	oai:doaj.org-article:cbf32919af56482c87b0f4f7be9aea632021-11-17T14:21:56ZIn vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes1388-02091744-511610.1080/13880209.2019.1656257https://doaj.org/article/cbf32919af56482c87b0f4f7be9aea632019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1656257https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Kaempferitrinis (KF) is a bioactive flavonoid and possesses numerous pharmacological activities. However, whether KF affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the effects of KF on eight major CYP isoforms in human liver microsomes (HLMs). Materials and methods: In vitro, HLMs were used to investigate the inhibitory effects of KF (100 μM) on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8), and corresponding probe substrates were used. Enzyme kinetic studies (0–50 μM of KF) were conducted to determine the inhibition mode of KF on CYP enzymes. Results: The results showed that KF inhibited the activity of CYP1A2, 3A4, and 2C9, with IC50 values of 20.56, 13.87, and 14.62 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that KF was not only a noncompetitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.11, 10.24, and 7.58 μM, respectively. In addition, KF is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 10.85/0.036 min/μM. Discussion: The in vitro studies of KF with CYP isoforms indicate that KF has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, 3A4, and 2C9. Conclusion: It is recommended that KF should not be used with other drugs metabolized by CYP1A2, 3A4, and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.Ning ZhangJing LiuZhixia ChenWenwen DouTaylor & Francis Grouparticlecyp1a2cyp3a4cyp2c9herb-drug interactionTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 571-576 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cyp1a2 cyp3a4 cyp2c9 herb-drug interaction Therapeutics. Pharmacology RM1-950
spellingShingle	cyp1a2 cyp3a4 cyp2c9 herb-drug interaction Therapeutics. Pharmacology RM1-950 Ning Zhang Jing Liu Zhixia Chen Wenwen Dou In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes
description	Context: Kaempferitrinis (KF) is a bioactive flavonoid and possesses numerous pharmacological activities. However, whether KF affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the effects of KF on eight major CYP isoforms in human liver microsomes (HLMs). Materials and methods: In vitro, HLMs were used to investigate the inhibitory effects of KF (100 μM) on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8), and corresponding probe substrates were used. Enzyme kinetic studies (0–50 μM of KF) were conducted to determine the inhibition mode of KF on CYP enzymes. Results: The results showed that KF inhibited the activity of CYP1A2, 3A4, and 2C9, with IC50 values of 20.56, 13.87, and 14.62 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that KF was not only a noncompetitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.11, 10.24, and 7.58 μM, respectively. In addition, KF is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 10.85/0.036 min/μM. Discussion: The in vitro studies of KF with CYP isoforms indicate that KF has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, 3A4, and 2C9. Conclusion: It is recommended that KF should not be used with other drugs metabolized by CYP1A2, 3A4, and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.
format	article
author	Ning Zhang Jing Liu Zhixia Chen Wenwen Dou
author_facet	Ning Zhang Jing Liu Zhixia Chen Wenwen Dou
author_sort	Ning Zhang
title	In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes
title_short	In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes
title_full	In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes
title_fullStr	In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes
title_full_unstemmed	In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes
title_sort	in vitro inhibitory effects of kaempferitrin on human liver cytochrome p450 enzymes
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/cbf32919af56482c87b0f4f7be9aea63
work_keys_str_mv	AT ningzhang invitroinhibitoryeffectsofkaempferitrinonhumanlivercytochromep450enzymes AT jingliu invitroinhibitoryeffectsofkaempferitrinonhumanlivercytochromep450enzymes AT zhixiachen invitroinhibitoryeffectsofkaempferitrinonhumanlivercytochromep450enzymes AT wenwendou invitroinhibitoryeffectsofkaempferitrinonhumanlivercytochromep450enzymes
_version_	1718425510075170816

In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes

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