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Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro

BACKGROUND: Descurainia sophia seeds have a variety of pharmacological functions and been widely used in traditional folk medicine. However, their effects on human drug metabolizing enzyme (DME) activities have not been elucidated. The present study investigated the inhibitory effects of an ethanol...

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Autores principales: Yi, Jin-Mu, Kim, Young Ah, Lee, You Jin, Bang, Ok-Sun, Kim, No Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683934/
https://www.ncbi.nlm.nih.gov/pubmed/26683337
http://dx.doi.org/10.1186/s12906-015-0965-0
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author Yi, Jin-Mu
Kim, Young Ah
Lee, You Jin
Bang, Ok-Sun
Kim, No Soo
author_facet Yi, Jin-Mu
Kim, Young Ah
Lee, You Jin
Bang, Ok-Sun
Kim, No Soo
author_sort Yi, Jin-Mu
collection PubMed
description BACKGROUND: Descurainia sophia seeds have a variety of pharmacological functions and been widely used in traditional folk medicine. However, their effects on human drug metabolizing enzyme (DME) activities have not been elucidated. The present study investigated the inhibitory effects of an ethanol extract of D. sophia seeds (EEDS) on human Phase I/II (DMEs) and P-glycoprotein (p-gp) in vitro. METHODS: The enzyme activities of human Phase I (cytochrome P450s, CYPs), Phase II (uridine diphosphate glucuronosyltransferases, UGTs) DMEs, and the drug transporter P-gp were determined in the presence of various concentrations of EEDS using commercially available luminogenic assay systems. The mode of enzyme inhibition and the inhibitory constant (K(i)) value of EEDS were graphically determined with Lineweaver-Burk double reciprocal plots and secondary plots, respectively. RESULTS: The enzyme activity assays showed that EEDS moderately inhibited the CYP1A2, CYP2C9, and CYP2C19 isoforms with half maximal inhibitory concentrations (IC(50)) of 47.3, 25.8, and 38.7 μg/mL, respectively. Graphical analyses with Lineweaver-Burk double reciprocal plots and secondary plots indicated that EEDS competitively inhibited CYP2C9 with a K(i) value of 19.8 μg/mL; however, it inhibited CYP2C9 and CYP2C19 in a mixed mode with K(i) values of 5.2, and 11.9 μg/mL, respectively. Other Phase I (CYP2C8, CYP2D6, and CYP3A4) and Phase II (UGT1A1 and UGT2B7) enzymes as well as P-gp were weakly or negligibly affected by EEDS with concentrations up to 500 μg/mL. CONCLUSIONS: EEDS is a selective inhibitor of CYP1A2, CYP2C9, and CYP2C19 with moderate enzymatic inhibition. Clinically, full consideration should be given to a potential toxic adverse effect from a herb-drug interaction when drugs that are particularly susceptible to CYP1A2, CYP2C9, or CYP2C19-mediated metabolism are taken together with EEDS. Characterization of metabolic profiles of specific herbal drugs could help consumers and medical specialists to use them safely as a complementary and alternative medicine.
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spelling pubmed-46839342015-12-19 Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro Yi, Jin-Mu Kim, Young Ah Lee, You Jin Bang, Ok-Sun Kim, No Soo BMC Complement Altern Med Research Article BACKGROUND: Descurainia sophia seeds have a variety of pharmacological functions and been widely used in traditional folk medicine. However, their effects on human drug metabolizing enzyme (DME) activities have not been elucidated. The present study investigated the inhibitory effects of an ethanol extract of D. sophia seeds (EEDS) on human Phase I/II (DMEs) and P-glycoprotein (p-gp) in vitro. METHODS: The enzyme activities of human Phase I (cytochrome P450s, CYPs), Phase II (uridine diphosphate glucuronosyltransferases, UGTs) DMEs, and the drug transporter P-gp were determined in the presence of various concentrations of EEDS using commercially available luminogenic assay systems. The mode of enzyme inhibition and the inhibitory constant (K(i)) value of EEDS were graphically determined with Lineweaver-Burk double reciprocal plots and secondary plots, respectively. RESULTS: The enzyme activity assays showed that EEDS moderately inhibited the CYP1A2, CYP2C9, and CYP2C19 isoforms with half maximal inhibitory concentrations (IC(50)) of 47.3, 25.8, and 38.7 μg/mL, respectively. Graphical analyses with Lineweaver-Burk double reciprocal plots and secondary plots indicated that EEDS competitively inhibited CYP2C9 with a K(i) value of 19.8 μg/mL; however, it inhibited CYP2C9 and CYP2C19 in a mixed mode with K(i) values of 5.2, and 11.9 μg/mL, respectively. Other Phase I (CYP2C8, CYP2D6, and CYP3A4) and Phase II (UGT1A1 and UGT2B7) enzymes as well as P-gp were weakly or negligibly affected by EEDS with concentrations up to 500 μg/mL. CONCLUSIONS: EEDS is a selective inhibitor of CYP1A2, CYP2C9, and CYP2C19 with moderate enzymatic inhibition. Clinically, full consideration should be given to a potential toxic adverse effect from a herb-drug interaction when drugs that are particularly susceptible to CYP1A2, CYP2C9, or CYP2C19-mediated metabolism are taken together with EEDS. Characterization of metabolic profiles of specific herbal drugs could help consumers and medical specialists to use them safely as a complementary and alternative medicine. BioMed Central 2015-12-18 /pmc/articles/PMC4683934/ /pubmed/26683337 http://dx.doi.org/10.1186/s12906-015-0965-0 Text en © Yi et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yi, Jin-Mu
Kim, Young Ah
Lee, You Jin
Bang, Ok-Sun
Kim, No Soo
Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro
title Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro
title_full Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro
title_fullStr Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro
title_full_unstemmed Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro
title_short Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro
title_sort effect of an ethanol extract of descurainia sophia seeds on phase i and ii drug metabolizing enzymes and p-glycoprotein activity in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683934/
https://www.ncbi.nlm.nih.gov/pubmed/26683337
http://dx.doi.org/10.1186/s12906-015-0965-0
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