Campomanesia guazumifolia infusion decreases human platelet aggregation by reducing cyclooxygenase 1 activity and its underlying mechanisms

Descrição

Tipo

Artigo de periódico

Título alternativo

A infusão de Campomanesia guazumifolia diminui a agregação plaquetária humana reduzindo a atividade da ciclooxigenase 1 e seus mecanismos subjacentes

Primeiro orientador

Membros da banca

Resumo

Campomanesia guazumifolia is a species from the Brazilian Cerrado, and its leaves are used by traditional medicine in the preparation of infusion. Its popular uses include antidiarrheal, hypocholesterolemic, and anti-inflammatory purposes. Here we studied the leaf infusion of Campomanesia guazumifolia (LICG) on platelet activity, investigating its role in the cyclooxygenase (COX) pathway. For this, the phytochemical composition, in vivo toxicity (using zebrafish) were evaluated and their effects were investigated on platelet reactivity using different agonists. To elucidate the possible mechanisms involved, we studied the impact of LICG on calcium mobilization, cyclic nucleotides and thromboxane levels, PKCβ2 phosphorylation, and COX inhibition. Furthermore, in silico studies showed the interactions of COX-1 with the compounds identified in LICG by molecular modeling. We describe for the first time that LICG acts by inhibiting platelet aggregation evoked by different physiological agonists, which results in a drastic reduction in intracellular calcium discharge without the involvement of cyclic nucleotide pathways. Furthermore, we showed that LICG appears to inhibit cyclooxygenase 1, reducing thromboxane A2 levels and PKCβ2 phosphorylation in human platelets, reinforced by similar interactions compared to a reference inhibitor at the catalytic site. This study demonstrates the antiplatelet effects of LICG via COX-1 and suggests that these agents may be therapeutic for preventing platelet-associated cardiovascular disease.

Abstract

Assunto

Guabiroba, Plantas dos cerrados, Flavonoides, Cálcio, Tromboxanas

Palavras-chave

Guabiroba, Plantas dos cerrados, Flavonoides, Cálcio, Tromboxanas

Citação

Curso

Endereço externo

https://www.sciencedirect.com/science/article/pii/S2212429223006065

Avaliação

Revisão

Suplementado Por

Referenciado Por