Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy

Abstract The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a nat...

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Autores principales:	Divyashree Ravishankar, Maryam Salamah, Alda Attina, Radhika Pothi, Thomas M. Vallance, Muhammad Javed, Harry F. Williams, Eman M. S. Alzahrani, Elena Kabova, Rajendran Vaiyapuri, Kenneth Shankland, Jonathan Gibbins, Katja Strohfeldt, Francesca Greco, Helen M. I. Osborn, Sakthivel Vaiyapuri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0eeaaa4bdcc84143851f1fbae8335e22
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spelling	oai:doaj.org-article:0eeaaa4bdcc84143851f1fbae8335e222021-12-02T12:31:47ZRuthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy10.1038/s41598-017-05936-32045-2322https://doaj.org/article/0eeaaa4bdcc84143851f1fbae8335e222017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05936-3https://doaj.org/toc/2045-2322Abstract The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents.Divyashree RavishankarMaryam SalamahAlda AttinaRadhika PothiThomas M. VallanceMuhammad JavedHarry F. WilliamsEman M. S. AlzahraniElena KabovaRajendran VaiyapuriKenneth ShanklandJonathan GibbinsKatja StrohfeldtFrancesca GrecoHelen M. I. OsbornSakthivel VaiyapuriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Divyashree Ravishankar Maryam Salamah Alda Attina Radhika Pothi Thomas M. Vallance Muhammad Javed Harry F. Williams Eman M. S. Alzahrani Elena Kabova Rajendran Vaiyapuri Kenneth Shankland Jonathan Gibbins Katja Strohfeldt Francesca Greco Helen M. I. Osborn Sakthivel Vaiyapuri Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
description	Abstract The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents.
format	article
author	Divyashree Ravishankar Maryam Salamah Alda Attina Radhika Pothi Thomas M. Vallance Muhammad Javed Harry F. Williams Eman M. S. Alzahrani Elena Kabova Rajendran Vaiyapuri Kenneth Shankland Jonathan Gibbins Katja Strohfeldt Francesca Greco Helen M. I. Osborn Sakthivel Vaiyapuri
author_facet	Divyashree Ravishankar Maryam Salamah Alda Attina Radhika Pothi Thomas M. Vallance Muhammad Javed Harry F. Williams Eman M. S. Alzahrani Elena Kabova Rajendran Vaiyapuri Kenneth Shankland Jonathan Gibbins Katja Strohfeldt Francesca Greco Helen M. I. Osborn Sakthivel Vaiyapuri
author_sort	Divyashree Ravishankar
title	Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
title_short	Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
title_full	Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
title_fullStr	Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
title_full_unstemmed	Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
title_sort	ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0eeaaa4bdcc84143851f1fbae8335e22
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Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy

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