polyphenol-rich extract, suggesting that some of the Bcr-Abl Species bioactive compounds present in the extract were in a position to cross the platelet cell membrane, probably targeting PKC or downstream molecules, i.e., signaling that occurs at the finish of the platelet activation pathway [57]. Similar data has been reported for a green tea flavonoid-rich extract that reduced platelet aggregation and integrin IIb3 activation upon stimulus with ADP, thrombin, or collagen [58]. Among one of the most active components present inside the polyphenol-rich extract are myricetin, gallic acid, and quercetin [57]. Their part in platelet activation and inhibition of aggregation will likely be individually discussed later. Aristoteliachilensis (Mol.) Stuntz, known as maqui, grows in central and southern Chile and has been utilised to get a long time for healthcare purposes [59]. Maqui’s most described actions are connected towards the high content of phenols in its fruit. We have lately identified and quantified a diverse range of compounds in maqui’s extracts from different variants (Luna Nueva, Morena, and Perla Negra) and diverse components on the plant (leaves, immature and mature fruits) [12]. The bioactive compounds found had been caffeic and gallic acids, quercetin, rutin, myricetin, catechin, epicatechin, and anthocyanins primarily derived from delphinidin, malvidin, petunidin, cyanidin, and peonidinanthocyanins [12]. Along with the identification from the compounds, our group evaluated the capacity of extracts from maqui’s variants to modulate platelet aggregation. Maqui extracts decreased platelet aggregation induced by a number of agonists, along with decreasing the exposure of Pselectin and CD63 at the platelet membrane [12]. five. Compounds That Inhibit Platelet Activation with no Affecting Bleeding Time Within this section, we go over the antiplatelet actions of bioactive compounds by means of key pathways (protein disulfide isomerase (PDI), mitogen-activated protein kinases (MAPKs), mitochondrial function, cyclic adenosine monophosphate (cAMP), Akt, and shear stressinduced platelet aggregation (SIPA)), and with no effects on bleeding time.Int. J. Mol. Sci. 2021, 22,4 of5.1. Protein Disulfide Isomerase ALDH3 medchemexpress Myricetin was tested in both platelet-rich plasma and washed platelets [57]. Platelet aggregation was inhibited within a dose-dependent manner by the flavonoid for either collagen or thrombin receptor-activating peptide-6 (TRAP-6)-induced aggregation. Additionally, fibrinogen binding and alpha-granule secretion induced by the collagen-related peptide is also inhibited by myricetin. All of the effects were accomplished at physiologically relevant concentrations [57]. It has been previously reported that myricetin strongly inhibits arachidonic acid-evoked platelet aggregation [60] without affecting cyclooxygenase activity in platelets [60]. We decided to think about PDI, an enzyme that participates inside the IIb3 activation necessary for platelet activation and aggregation processes, a potential target for the flavonoid effect [61]. Myricetin, possibly resulting from non-covalent bonds, can bind to thiol isomerases and inhibits the reductase activity of PDI and endoplasmic reticulum (ER) esident protein 57 (ERp57). Even so, preclinical research demonstrate that deficiency in platelet ERp57 resulted in improved tail bleeding occasions and delayed thrombus formation [62]. When in comparison to quercetin, a flavonoid with a comparable chemical structure, the observed effects of myricetin on platelet activation have been comparable [63]. Quercetin reduces thrombin-ind