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

Campomanesia guazumifolia is a species from the Brazilian Cerrado, and its leaves are used by traditional med-icine 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 ac-tivity, 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, PKC & beta;2 phosphorylation, and COX inhibition. Furthermore, in silico studies showed the interactions of COX-1 with the compounds identified in LICG by mo-lecular 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 cyclo-oxygenase 1, reducing thromboxane A2 levels and PKC & beta;2 phosphorylation in human platelets, reinforced by similar interactions compared to a reference inhibitor at the catalytic site. This study demonstrates the anti-platelet effects of LICG via COX-1 and suggests that these agents may be therapeutic for preventing platelet-associated cardiovascular disease.