cial product)-In vitro (washed human platelets) In vivo (C57BL/6J mice)0.50Without prolonging bleeding time in mice[97]Delphinidin-3-glucoside (comercial product)Fruit and vegetables: mulberries, grapes, blackberries, and red cabbage.-In vitro (gell-filtered human and murine platelets) In vivo (C57BL/6J mice)0.50Did not significantly have an effect on bleeding time in mice[98]-Int. J. Mol. Sci. 2021, 22,13 ofTable 1. Contpound All-natural Sources Tetramethylpyrazine (comercial item) Ligusticum chuanxiong, cacao beans, soybeans. MC1R custom synthesis effects and Proposed Mechanisms Inhibits shear-induced platelet aggregation below reasonably high shear rate Inhibited P-selectin surface expression and microparticle release In Vitro or In Vivo Effects Concentration Ranges In Vitro Effects on Bleeding Bleeding was not determined, but no considerable influences have been observed below comparatively low shear prices ReferenceIn vitro (PRP from humans)0.9.7 mM[99]- All-natural sources independent on the study described. Nd.: not determined. ADP: adenosine diphosphate, ADP: adenosine diphosphate, ATP: adenosine triphosphate, cAMP: cyclic adenosine monophosphate, CRP: collagen-related peptide, GP: glycoprotein, HUVEC: human umbilical vein endothelial cells, ITAM: immunoreceptor tyrosine-based activation motif, MAPKs: mMitogen-activated protein kinases, mtDNA: mitochondrial DNA, OH hydroxyl radical, PDI: protein disulfide isomerase, PKA: protein kinase A, PKC: protein kinase C, PLC: phospholipase C, PRP: pPlatelet-rich plasma, ROS: reactive oxygen species, SIPA: shear stress-induced platelet aggregation, TRAP-6: thrombin receptor-activating peptide-6, TXA2: thromboxane A2, VASP: vasodilator-stimulated phosphoprotein, vWF: Von Willebrand HSV-1 Species aspect.Int. J. Mol. Sci. 2021, 22,14 of6. Prospective and Pitfalls in the Therapeutic Use of Antiplatelet Bioactive Compounds Most of the data presented above have been obtained from observational studies applying platelet-rich plasma, washed platelets, or blood samples in vitro or employing mice models [102]. Furthermore, the bioactive compounds have been obtained commercially or present in aqueous, hydroalcoholic, or ethanolic extracts from distinctive plant leaves or fruits. Hence, implementations of clinical trials with either the pure compounds or the extracts are essential to the development of novel, all-natural antithrombotic drugs. A vital issue to be evaluated for the usage of the extracts from plants or fruit will be the style of solvents utilized to get the mixture of bioactive compounds, i.e., methanol, ethanol, and hydroalcoholic mixtures. Also, it truly is relevant to carry out the right and precise determination for each composition and quantities with the compounds to avoid toxicity nor non-desired unwanted effects. Most of the accessible clinical trials use foods, mainly from berries, cocoa, or chocolate, and much less regularly extracts from berries and green tea [102]. It can be important to point out the lack of trials using the type of extracts presented ahead of as an essential pitfall of your use of these nutraceutical extracts with antiplatelet or antithrombotic prospective. Moreover, half in the trials performed within the last 20 years have been performed on healthier volunteers, though significantly less than 20 involve men and women with at the very least a single cardiometabolic risk element. From the total variety of trials with polyphenols inside the final 20 years, despite the fact that 20 analyzed vascular and endothelium responses, there is a lack of trials on platelet function and thrombosis [102]. Ultimately, an extra relevant fact for t
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