polyphenol-rich extract, suggesting that a few of the bioactive compounds present in the extract have been in a position to cross the platelet cell membrane, likely targeting PKC or downstream molecules, i.e., signaling that happens at the end in the platelet activation pathway [57]. Similar data has been reported for any green tea flavonoid-rich extract that reduced platelet aggregation and integrin IIb3 activation upon stimulus with ADP, thrombin, or collagen [58]. Among probably the most active elements present within the polyphenol-rich extract are myricetin, gallic acid, and quercetin [57]. Their role in platelet activation and inhibition of aggregation will likely be individually discussed later. Aristoteliachilensis (Mol.) Stuntz, generally known as maqui, grows in central and southern Chile and has been applied for any extended time for medical purposes [59]. Maqui’s most described actions are associated for the higher content material of phenols in its fruit. We’ve recently identified and quantified a diverse wide variety of compounds in maqui’s extracts from distinctive variants (Luna Nueva, Morena, and Perla Negra) and distinct components of your plant (leaves, imKinesin-7/CENP-E Purity & Documentation mature and mature fruits) [12]. The bioactive compounds found have been caffeic and gallic acids, quercetin, rutin, myricetin, catechin, epicatechin, and anthocyanins primarily derived from delphinidin, malvidin, petunidin, cyanidin, and peonidinanthocyanins [12]. As well as the identification with the compounds, our group evaluated the Bax MedChemExpress capacity of extracts from maqui’s variants to modulate platelet aggregation. Maqui extracts decreased platelet aggregation induced by various agonists, as well as decreasing the exposure of Pselectin and CD63 at the platelet membrane [12]. 5. Compounds That Inhibit Platelet Activation with no Affecting Bleeding Time In this section, we talk about the antiplatelet actions of bioactive compounds by way of crucial 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,four of5.1. Protein Disulfide Isomerase myricetin was tested in each platelet-rich plasma and washed platelets [57]. Platelet aggregation was inhibited inside a dose-dependent manner by the flavonoid for either collagen or thrombin receptor-activating peptide-6 (TRAP-6)-induced aggregation. Moreover, fibrinogen binding and alpha-granule secretion induced by the collagen-related peptide is also inhibited by myricetin. All the effects have been completed at physiologically relevant concentrations [57]. It has been previously reported that myricetin strongly inhibits arachidonic acid-evoked platelet aggregation [60] with no affecting cyclooxygenase activity in platelets [60]. We decided to consider PDI, an enzyme that participates within the IIb3 activation needed for platelet activation and aggregation processes, a prospective target for the flavonoid impact [61]. Myricetin, possibly on account of non-covalent bonds, can bind to thiol isomerases and inhibits the reductase activity of PDI and endoplasmic reticulum (ER) esident protein 57 (ERp57). On the other hand, preclinical studies demonstrate that deficiency in platelet ERp57 resulted in elevated tail bleeding instances and delayed thrombus formation [62]. When when compared with quercetin, a flavonoid with a equivalent chemical structure, the observed effects of myricetin on platelet activation were comparable [63]. Quercetin reduces thrombin-ind