# Antiplatelet Activity of Phenolic Compounds-Fortified Merlot Wine and Pure Phenolic Compounds
###### Abstract  
Red wines and their compace are valuable sources of phenolic compounds (PCs), which have been proposed as potential contributors to their cardioprotective effect through the inhibition of platelet aggregation. The antiplatelet activity of an extract depends on its chemical composition, specifically the presence of certain phenolic compounds, as well as the interactions between them affecting biological activity. In order to assess the effect on platelet aggregation, we investigated the effect of the grape pomace PC enrichment of a Merlot wine, as well as the effect of the five major phenolic compounds present in wine extracts: caffeic acid, gallic acid, quercetin, epicatechin, and catechin. We analyzed how their combination influenced platelet aggregation. We found that the fortified wine sample with the highest PC content (W8) exhibited a potent antiplatelet effect in aggregation and platelet activation assays induced by the agonists TRAP-6, collagen, and ADP, with its activity being most potent against the latter agonist (78 \(\pm\) 4%). Among the evaluated phenolic compounds, quercetin showed the highest antiplatelet potential against all three agonists studied, while gallic acid showed minimal antiplatelet effect. These findings suggest that the cardioprotective effect of wines is related to their chemical composition and the synergy among phenolic compounds. However, further research is required to fully understand the underlying mechanisms and clinical relevance of this activity. Keywords:wine extracts; platelet aggregation; phenolic compounds +
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bleeding [5]. The search for superior and safer antiplatelet agents constitutes a significant therapeutic challenge. Cohorts from the USA, Japan, and Northern and Southern Europe show that nutrition is the cornerstone that promotes health, highlighting the importance of the Mediterranean Diet [6], which has been characterized by a high consumption of vegetables, legumes, fruits, nuts, cereals, fish, shellfish, and poultry as a source of protein, and olive oil, nuts, and a low or moderate consumption of red wine [6; 7]. Dies rich in polyphenols have shown a great impact on the vascular system, improving both platelet and endothelial functions [8]. It is important to highlight that low or moderate wine consumption is understood to be between one and two drinks/day or \(\sim\)150 and 300 mL/day [6; 9]. It is important to consider that new guidelines have been published in Europe, indicating that consumers should control their drinking habits without exceeding the healthy threshold of alcohol consumption (30-40 g of alcohol/day in men and 10-20 g of alcohol/day in women) [10]. Phenolic compounds play an important role in enology since they are related to the organoleptic characteristics of wine, such as color, aroma, astringency, and bitterness [11]. The final phenolic content and the phenolic profile of the wines depend on the viticulture processes and the environmental conditions associated with the grape-growing region [12; 13]. The antioxidant capacity of phenolic compounds depends on their chemical structures and the interactions between them [14]. Anthocyanins and flavonoids are the main fractions of phenolic compounds in wine. The content of these compounds depends on several factors, and the specific profile of anthocyanins depends on the crop and is related to its genetic information [12]. The consumption of phenolic compounds found in red wines and grape pomace is associated with a lower prevalence of cardiovascular diseases, although the preventive mechanism is still not fully understood [15]. It has been proposed that the phenolic compounds present in red wines may enhance endothelium-dependent vasodilation, increase plasma antioxidants, and inhibit platelet aggregation [16].