**5. Antiplatelet Activity of the Compounds in Maqui**

Several fruits such as red grapes, strawberries, kiwis, and pineapples have been shown to exert antiplatelet effects [63]. The most commonly investigated berries with antiplatelet potential have been grapes, aronia berries, and sea buckthorn berries, which contain phenolic compounds such as hippuric acid, pyrogallol, catechol, and resorcinol which inhibit collagen-stimulated platelets at a concentration of 100 μM [83,84]. A combination of extracts from different berries (blueberries, strawberry puree, cranberries, blackcurrant puree, and raspberry juice) showed an antiplatelet effect when using ADP and collagen as agonists, in platelets from healthy adults who consumed moderate amounts of berries for 8 weeks [84,85]. Another in vivo study, in whole blood, showed that the combination of grape seed and skin extracts reduced collagen-induced platelet aggregation to a greater extent than either extract alone, showing the importance of synergistic inhibitory actions at physiological levels [84,86]. Cranberry juice also inhibited ADP- and collagen-induced platelet aggregation after four days of consumption four times a day [87]. In addition, strawberry extract (0.1–1 mg/mL) in an in vivo model inhibits platelet aggregation induced by arachidonic acid (AA) and ADP in a dose-dependent manner [44]. Results of in vitro and ex vivo studies have reported that polyphenols present in red grape and purple grape juices inhibit platelet aggregation induced by ADP, thrombin, collagen, epinephrine, and AA [85,88–91]. Chlorogenic acid, a polyphenol present in cherries, apples, kiwis, eggplants, plums, and coffee, also exhibits antiplatelet activity [92].

The few studies about antiplatelet activity in Maqui are recent [93]. The aggregation and platelet secretion induced by ADP and collagen were significantly inhibited by leaf and immature fruit extracts of the varieties "Luna Nueva" and "Morena". These extracts also reduced oxidative stress, an effect that might be related to the high content of antioxidant compounds [20]. The chemical characterization allowed us to identify several compounds with known antiplatelet potential, such as caffeic acid, quercetin, isorhamnetin, kaempferol, and rutin, among others. The varieties differ in the composition and concentration of phenolic compounds, supporting the fact that extracts from different genotypes and parts

of the tree, e.g., immature compared to mature fruit, vary in their antiplatelet activities. The participation of each bioactive compound with antiplatelet activity was also investigated using Pearson's statistical analysis. The results showed that the levels of phenolic compounds are responsible for the antiplatelet effects of Maqui [93].

Although this berry has been attributed with a wide biological potential, a gap can be seen in the literature regarding its antiplatelet properties. However, its rich chemical composition clearly shows that the presence of chemical compounds with high antiplatelet potential can give Maqui a prominent potential in the development of new antiplatelet agents. Table 3 summarizes some in vitro and in vivo studies of the antiplatelet activity of bioactive compounds identified in Maqui, i.e., anthocyanins, flavonoids, and phenolic acids that have important antiaggregant activity against several agonists, e.g., TRAP-6, ADP, collagen, and arachidonic acid (AA).
