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Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase

Members of the Viola genus play important roles in traditional Asian herbal medicine. This study investigates the ability of Viola odorata L. extracts to inhibit Na(+),K(+)-ATPase, an essential animal enzyme responsible for membrane potential maintenance. The root extract of V. odorata strongly inhi...

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Autores principales: Heger, Tomas, Zatloukal, Marek, Kubala, Martin, Strnad, Miroslav, Gruz, Jiri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055044/
https://www.ncbi.nlm.nih.gov/pubmed/35487935
http://dx.doi.org/10.1038/s41598-022-11086-y
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author Heger, Tomas
Zatloukal, Marek
Kubala, Martin
Strnad, Miroslav
Gruz, Jiri
author_facet Heger, Tomas
Zatloukal, Marek
Kubala, Martin
Strnad, Miroslav
Gruz, Jiri
author_sort Heger, Tomas
collection PubMed
description Members of the Viola genus play important roles in traditional Asian herbal medicine. This study investigates the ability of Viola odorata L. extracts to inhibit Na(+),K(+)-ATPase, an essential animal enzyme responsible for membrane potential maintenance. The root extract of V. odorata strongly inhibited Na(+),K(+)-ATPase, while leaf and seeds extracts were basically inactive. A UHPLC-QTOF-MS/MS metabolomic approach was used to identify the chemical principle of the root extract’s activity, resulting in the detection of 35,292 features. Candidate active compounds were selected by correlating feature area with inhibitory activity in 14 isolated fractions. This yielded a set of 15 candidate compounds, of which 14 were preliminarily identified as procyanidins. Commercially available procyanidins (B1, B2, B3 and C1) were therefore purchased and their ability to inhibit Na(+),K(+)-ATPase was investigated. Dimeric procyanidins B1, B2 and B3 were found to be inactive, but the trimeric procyanidin C1 strongly inhibited Na(+),K(+)-ATPase with an IC(50) of 4.5 µM. This newly discovered inhibitor was docked into crystal structures mimicking the Na(3)E(1)∼P·ADP and K(2)E(2)·P(i) states to identify potential interaction sites within Na(+),K(+)-ATPase. Possible binding mechanisms and the principle responsible for the observed root extract activity are discussed.
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spelling pubmed-90550442022-05-01 Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase Heger, Tomas Zatloukal, Marek Kubala, Martin Strnad, Miroslav Gruz, Jiri Sci Rep Article Members of the Viola genus play important roles in traditional Asian herbal medicine. This study investigates the ability of Viola odorata L. extracts to inhibit Na(+),K(+)-ATPase, an essential animal enzyme responsible for membrane potential maintenance. The root extract of V. odorata strongly inhibited Na(+),K(+)-ATPase, while leaf and seeds extracts were basically inactive. A UHPLC-QTOF-MS/MS metabolomic approach was used to identify the chemical principle of the root extract’s activity, resulting in the detection of 35,292 features. Candidate active compounds were selected by correlating feature area with inhibitory activity in 14 isolated fractions. This yielded a set of 15 candidate compounds, of which 14 were preliminarily identified as procyanidins. Commercially available procyanidins (B1, B2, B3 and C1) were therefore purchased and their ability to inhibit Na(+),K(+)-ATPase was investigated. Dimeric procyanidins B1, B2 and B3 were found to be inactive, but the trimeric procyanidin C1 strongly inhibited Na(+),K(+)-ATPase with an IC(50) of 4.5 µM. This newly discovered inhibitor was docked into crystal structures mimicking the Na(3)E(1)∼P·ADP and K(2)E(2)·P(i) states to identify potential interaction sites within Na(+),K(+)-ATPase. Possible binding mechanisms and the principle responsible for the observed root extract activity are discussed. Nature Publishing Group UK 2022-04-29 /pmc/articles/PMC9055044/ /pubmed/35487935 http://dx.doi.org/10.1038/s41598-022-11086-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Heger, Tomas
Zatloukal, Marek
Kubala, Martin
Strnad, Miroslav
Gruz, Jiri
Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase
title Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase
title_full Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase
title_fullStr Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase
title_full_unstemmed Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase
title_short Procyanidin C1 from Viola odorata L. inhibits Na(+),K(+)-ATPase
title_sort procyanidin c1 from viola odorata l. inhibits na(+),k(+)-atpase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055044/
https://www.ncbi.nlm.nih.gov/pubmed/35487935
http://dx.doi.org/10.1038/s41598-022-11086-y
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