Abstract
With the diet, we ingest nutrients capable of modulating platelet function, which plays a crucial role in developing cardiovascular events, one of the leading causes of mortality worldwide. Studies that demonstrate the antiplatelet and antithrombotic potential of bioactive compounds are vital to maintaining good cardiovascular health. In this work, we evaluate the flavonol isorhamnetin’s antiplatelet effect on human platelets, using collagen, thrombin receptor activator peptide 6 (TRAP-6), and phorbol myristate acetate (PMA) as agonists. Isorhamnetin induced a significant inhibition on collagen- and TRAP-6-induced platelet aggregation, with half-maximum inhibitory concentration (IC50) values of 8.1 ± 2.6 and 16.1 ± 11.1 µM, respectively; while it did not show cytotoxic effect. Isorhamnetin reduced adenosine triphosphate levels (ATP) in platelets stimulated by collagen and TRAP-6. We also evidenced that isorhamnetin’s antiplatelet activity was related to the inhibition of mitochondrial function without effect on reactive oxygen species (ROS) levels. Additionally, we investigated isorhamnetin’s effect on thrombus formation in vitro under flow conditions on the damaged vessel wall. In this context, we demonstrate that isorhamnetin at 20 µM induced a significant inhibition on platelet deposition, confirming its antithrombotic effect. Our findings corroborate the antiplatelet and antithrombotic potential of isorhamnetin present in many foods of daily consumption.
Highlights
Introduction published maps and institutional affilThe number of deaths from diet-related cardiovascular events increased between 2010 and 2016 [1]
We study if the isorhamnetin has an antiplatelet activity through the inhibition of mitochondrial bioenergetics
Due to isorhamnetin’s action on the mitochondria, an increase in intraplatelet calcium levels was observed. These results show that isorhamnetin decreased platelet activation via inhibition of mitochondrial function, which is associated with potent non-selective inhibition of platelet aggregation induced by thrombin receptor activator peptide 6 (TRAP-6) and collagen
Summary
Introduction published maps and institutional affilThe number of deaths from diet-related cardiovascular events increased between 2010 and 2016 [1]. Rich mainly in fruits and vegetables, more than 30% of deaths could be prevented [2,3]. Numerous investigations indicate that the dietary intake of flavonoids, such as quercetin and its derivatives present in fruits and vegetables, can reduce the risk of cardiovascular diseases (CVD) [4,5]. Isorhamnetin (3-methyl quercetin, molecular formula: C16 H12 O7 ) is a methylated flavonol present in leaves, flowers, and fruits of many plants [5,6,7]. This is the case of Phaseolus vulgaris L., belonging to the group of legume plants consumed in the five iations
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