# Antiplatelet Activity of Phenolic Compounds-Fortified Merlot Wine and Pure Phenolic Compounds
## 4 Discussion  
Parallel to the improvement in life expectancy, deaths from CVD have been increasing [23]. Platelet hyperactivity has been increasingly linked to the development and complication of certain CVDs, including atherosclerosis, thrombosis, peripheral arterial disease, myocardial infarction, and ischemic stroke [8]. Through inhibition of these activations and aggregation processes, antiplatelet therapy has proven to be a mainstay in the prevention and treatment of CVD events [4]. Polyphenolic compounds present in products of plant origin play a central role in many scientific studies due to their potential health benefits, mainly due to their positive impact on CVDs [8; 24]. Phenolic compounds have been shown to have antiplatelet capabilities and a positive impact on CVD management, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects [25]. Quercetin, after ingestion, is metabolized into several compounds, including isorhamentin and tamarixetin. Research has shown that these metabolites retain potent antithrombotic activities. They effectively inhibit platelet aggregation and thrombus formation, similar to quercetin itself [26]. On the other hand, catechin is rapidly metabolized into glucuronide and sulfate conjugates after absorption. These metabolites have been shown to maintain bioactivity and contribute to the beneficial cardiovascular effects associated with catechin intake [27; 28]. The absorption and metabolism of these dietary phenolic compounds determine the extent of their health benefits, which in turn are determined by their structure (conjugation with other phenols, degree of glycosylation/acylation), solubility,and molecular size. Its effectiveness decreases with the replacement of the hydroxyl groups in its structure by sugars; therefore, aglycones exhibit more potent activities than their corresponding glycosides [8]. The antiplatelet activity of an extract is strongly influenced by its chemical composition. It has been described that the presence of bioactive compounds is responsible for the activity of different samples [20; 22]. In particular, phenolic compounds have been largely attributed to extensive cardiovascular benefits [29]. Its effects are strongly related to its chemical structure and the interactions that the compounds can exert, whether synergistic (when the effect increases), additive (when the effect is maintained), or antagonistic (when the effect decreases) [14]. The antiplatelet ability of phenolic compounds in vivo is poor. Therefore, despite the current advances, more studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic intervention [13]. In our study, we evaluated different pathways of platelet activation induced by platelet agonists: collagen, TRAP-6, and ADP. As expected, there were differences in antiplatelet potential. Platelets have previously been shown to be activated by different activators through complex signaling pathways [26; 30]. Thrombin, thromboxane A, collagen, and ADP are some of the key agonists of platelet activation that lie at the intersection of a plethora of inflammatory pathways that modulate proinflammatory and coagulation processes [3]. ADP interacts with the family of purinergic receptors (P2Y1, P2Y12, and P2X1), while TRAP-6 acts on the thrombin receptor PAR1 [31]. Wine sample 8 showed a potent antiplatelet effect against the agonists TRAP-6, collagen, and ADP, with its activity being more potent against the latter agonist (78 \(\pm\) 4% percentage of platelet inhibition). Although F8 showed greater antiplatelet activity than the rest of the wines evaluated, this effect was indistinct depending on the agonist that triggered platelet aggregation, with a lower IC\({}_{50}\) compared to TRAP-6 (0.30 \(\pm\) 0.08).