Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product
Abstract A commercial Rhodiola rosea ( R. rosea ) product has previously demonstrated CYP 2C9 inhibition in humans. The purpose of this study was to provide in vitro inhibitory data for this particular interaction and to classify the mechanism of the interaction. Another aim was to examine the in vi...
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crwiley:10.1002/prp2.324 2024-09-09T19:22:19+00:00 Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product Thu, Ole Kristian Forstrønen Spigset, Olav Hellum, Bent 2017 http://dx.doi.org/10.1002/prp2.324 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprp2.324 https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1002/prp2.324 en eng Wiley http://creativecommons.org/licenses/by/4.0/ Pharmacology Research & Perspectives volume 5, issue 4 ISSN 2052-1707 2052-1707 journal-article 2017 crwiley https://doi.org/10.1002/prp2.324 2024-08-09T04:24:41Z Abstract A commercial Rhodiola rosea ( R. rosea ) product has previously demonstrated CYP 2C9 inhibition in humans. The purpose of this study was to provide in vitro inhibitory data for this particular interaction and to classify the mechanism of the interaction. Another aim was to examine the in vitro influence of ethanol on the CYP 2C9 activity. Human CYP 2C9 (wild type) isolated from a baculovirus‐infected cell system was incubated with 0.8 μ mol/L losartan for 20 min. Sulfaphenazole was used as a positive control. The commercial R. rosea product “Arctic Root” was used as test inhibitor. Formation of the CYP 2C9‐produced losartan metabolite EXP ‐3174 was determined by validated LC ‐ MS / MS methodology. Possible mechanism‐based (irreversible) inhibition was evaluated using time‐ and NADPH ‐dependent inhibition assays. Kinetic constants ( K m , V max , and K i ) were calculated from a Lineweaver‐Burk plot. Mode of inhibition was determined. CYP 2C9 was inhibited by “Arctic Root” with an IC 50 (extract concentration yielding 50% reduction in enzyme activity) of 19.2 ± 2.7 μ g/mL. Inhibitor concentrations of 20 μ g/mL and 40 μ g/mL yielded K i values of 16.37 μ g/mL and 5.59 μ g/mL, respectively. The Lineweaver‐Burk plot showed noncompetitive inhibition mode. No time‐ or NADPH ‐dependent inhibition was observed. The presence of ethanol inhibited CYP 2C9 activity in a concentration‐dependent manner. In conclusion, the commercial R. rosea product “Arctic Root” demonstrated noncompetitive inhibition of CYP 2C9 in vitro. Further work identifying the constituents responsible for this inhibition is needed. Article in Journal/Newspaper Arctic Wiley Online Library Arctic Pharmacology Research & Perspectives 5 4 |
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Abstract A commercial Rhodiola rosea ( R. rosea ) product has previously demonstrated CYP 2C9 inhibition in humans. The purpose of this study was to provide in vitro inhibitory data for this particular interaction and to classify the mechanism of the interaction. Another aim was to examine the in vitro influence of ethanol on the CYP 2C9 activity. Human CYP 2C9 (wild type) isolated from a baculovirus‐infected cell system was incubated with 0.8 μ mol/L losartan for 20 min. Sulfaphenazole was used as a positive control. The commercial R. rosea product “Arctic Root” was used as test inhibitor. Formation of the CYP 2C9‐produced losartan metabolite EXP ‐3174 was determined by validated LC ‐ MS / MS methodology. Possible mechanism‐based (irreversible) inhibition was evaluated using time‐ and NADPH ‐dependent inhibition assays. Kinetic constants ( K m , V max , and K i ) were calculated from a Lineweaver‐Burk plot. Mode of inhibition was determined. CYP 2C9 was inhibited by “Arctic Root” with an IC 50 (extract concentration yielding 50% reduction in enzyme activity) of 19.2 ± 2.7 μ g/mL. Inhibitor concentrations of 20 μ g/mL and 40 μ g/mL yielded K i values of 16.37 μ g/mL and 5.59 μ g/mL, respectively. The Lineweaver‐Burk plot showed noncompetitive inhibition mode. No time‐ or NADPH ‐dependent inhibition was observed. The presence of ethanol inhibited CYP 2C9 activity in a concentration‐dependent manner. In conclusion, the commercial R. rosea product “Arctic Root” demonstrated noncompetitive inhibition of CYP 2C9 in vitro. Further work identifying the constituents responsible for this inhibition is needed. |
format |
Article in Journal/Newspaper |
author |
Thu, Ole Kristian Forstrønen Spigset, Olav Hellum, Bent |
spellingShingle |
Thu, Ole Kristian Forstrønen Spigset, Olav Hellum, Bent Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product |
author_facet |
Thu, Ole Kristian Forstrønen Spigset, Olav Hellum, Bent |
author_sort |
Thu, Ole Kristian Forstrønen |
title |
Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product |
title_short |
Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product |
title_full |
Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product |
title_fullStr |
Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product |
title_full_unstemmed |
Noncompetitive inhibition of human CYP2C9 in vitro by a commercial Rhodiola rosea product |
title_sort |
noncompetitive inhibition of human cyp2c9 in vitro by a commercial rhodiola rosea product |
publisher |
Wiley |
publishDate |
2017 |
url |
http://dx.doi.org/10.1002/prp2.324 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprp2.324 https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1002/prp2.324 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Pharmacology Research & Perspectives volume 5, issue 4 ISSN 2052-1707 2052-1707 |
op_rights |
http://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.1002/prp2.324 |
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Pharmacology Research & Perspectives |
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5 |
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4 |
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