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Título:

Myricetin, the main flavonoid in syzygium cumini leaf, is a novel inhibitor of platelet thiol isomerases PDI and ERp5

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Autor:

Gaspar, Renato Simões
da Silva, Samira Abdalla
Stapleton, Jennifer
Fontelles, João Lucas de Lima
Sousa, Hiran Reis
Chagas, Vinicyus Teles
Alsufyani, Shuruq
Trostchansky, Andrés
Gibbins, Jonathan M.
Paes, Antonio Marcus de Andrade

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Tipo de documento:

Artículo

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Palabras clave:

Syzygium cumini
Antithrombotic agents
Oxidation-reduction
Platelet
Platelet aggregation inhibitors

Descriptores:

TROMBOSIS
ENZIMAS
PLAQUETAS
FLAVONOIDES
SYZYGIUM
COMPUESTOS DE SULFHIDRILO
PROTEÍNA DISULFURO ISOMERASAS
COAGULACIÓN SANGUÍNEA
INHIBIDORES DE AGREGACIÓN PLAQUETARIA
OXIDACIÓN-REDUCCIÓN
FIBRINOLÍTICOS

Año de publicación:

2020

Contenido:

Resumen:

Background: Flavonoids have been characterized as a prominent class of compounds to treat thrombotic diseases through the inhibition of thiol isomerases. Syzygium cumini is a flavonoid-rich medicinal plant that contains myricetin and gallic acid. Little is known about the potential antiplatelet properties of S. cumini and its constituent flavonoids. Objective: To evaluate the antiplatelet effects and mechanism of action of a polyphenol-rich extract (PESc) from S. cumini leaf and its most prevalent polyphenols, myricetin and gallic acid. Methods: PESc, myricetin, and gallic acid were incubated with platelet-rich plasma and washed platelets to assess platelet aggregation and activation. In vitro platelet adhesion and thrombus formation as well as in vivo bleeding time were performed. Finally, myricetin was incubated with recombinant thiol isomerases to assess its potential to bind and inhibit these, while molecular docking studies predicted possible binding sites. Results: PESc decreased platelet activation and aggregation induced by different agonists. Myricetin exerted potent antiplatelet effects, whereas gallic acid did not. Myricetin reduced the ability of platelets to spread on collagen, form thrombi in vitro without affecting hemostasis in vivo. Fluorescence quenching studies suggested myricetin binds to different thiol isomerases with similar affinity, despite inhibiting only protein disulfide isomerase (PDI) and ERp5 reductase activities. Finally, molecular docking studies suggested myricetin formed non-covalent bonds with PDI and ERp5. Conclusions: PESc and its most abundant flavonoid myricetin strongly inhibit platelet function. Additionally, myricetin is a novel inhibitor of ERp5 and PDI, unveiling a new therapeutic perspective for the treatment of thrombotic disorders.

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Frontiers Media

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Frontiers in Pharmacology, 2020;10

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Citación:

Gaspar R, da Silva S, Stapleton J y otros. Myricetin, the main flavonoid in syzygium cumini leaf, is a novel inhibitor of platelet thiol isomerases PDI and ERp5. Frontiers in Pharmacology [en línea]. 2020;10.15 p.

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Licencia Creative Commons Atribución (CC - By 4.0)

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