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Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators
Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting K(Ca)1.1 and Ca(V)1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a ser...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324545/ https://www.ncbi.nlm.nih.gov/pubmed/35889386 http://dx.doi.org/10.3390/molecules27144505 |
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author | Cuong, Nguyen Manh Son, Ninh The Nhan, Ngu Truong Fukuyama, Yoshiyasu Ahmed, Amer Saponara, Simona Trezza, Alfonso Gianibbi, Beatrice Vigni, Ginevra Spiga, Ottavia Fusi, Fabio |
author_facet | Cuong, Nguyen Manh Son, Ninh The Nhan, Ngu Truong Fukuyama, Yoshiyasu Ahmed, Amer Saponara, Simona Trezza, Alfonso Gianibbi, Beatrice Vigni, Ginevra Spiga, Ottavia Fusi, Fabio |
author_sort | Cuong, Nguyen Manh |
collection | PubMed |
description | Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting K(Ca)1.1 and Ca(V)1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Dalbergia tonkinensis Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba(2+) currents through Ca(V)1.2 channels (I(Ba1.2)) were blocked in a concentration-dependent manner by sativanone, 3′-O-methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside], ambocin, butin, and biochanin A increased I(KCa1.1). In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, Dalbergia tonkinensis is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs. |
format | Online Article Text |
id | pubmed-9324545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93245452022-07-27 Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators Cuong, Nguyen Manh Son, Ninh The Nhan, Ngu Truong Fukuyama, Yoshiyasu Ahmed, Amer Saponara, Simona Trezza, Alfonso Gianibbi, Beatrice Vigni, Ginevra Spiga, Ottavia Fusi, Fabio Molecules Article Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting K(Ca)1.1 and Ca(V)1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Dalbergia tonkinensis Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba(2+) currents through Ca(V)1.2 channels (I(Ba1.2)) were blocked in a concentration-dependent manner by sativanone, 3′-O-methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside], ambocin, butin, and biochanin A increased I(KCa1.1). In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, Dalbergia tonkinensis is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs. MDPI 2022-07-14 /pmc/articles/PMC9324545/ /pubmed/35889386 http://dx.doi.org/10.3390/molecules27144505 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cuong, Nguyen Manh Son, Ninh The Nhan, Ngu Truong Fukuyama, Yoshiyasu Ahmed, Amer Saponara, Simona Trezza, Alfonso Gianibbi, Beatrice Vigni, Ginevra Spiga, Ottavia Fusi, Fabio Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators |
title | Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators |
title_full | Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators |
title_fullStr | Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators |
title_full_unstemmed | Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators |
title_short | Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators |
title_sort | vietnamese dalbergia tonkinensis: a promising source of mono- and bifunctional vasodilators |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324545/ https://www.ncbi.nlm.nih.gov/pubmed/35889386 http://dx.doi.org/10.3390/molecules27144505 |
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