Grape Seed Extracts Inhibit Platelet Aggregation by Inhibiting Protein Tyrosine Phosphatase

Abstract

Platelets play an important role in various thrombotic diseases, including myocardial infarction. Because red wine consumption is inversely associated with death due to ischemic heart diseases, the effects of grape components on platelet function have been extensively investigated. Grape seed extracts (GSEs) reportedly inhibit platelet aggregation; however, the underlying mechanism has not been elucidated. We discovered that GSEs inhibit platelet aggregation induced by collagen and thrombin-receptor agonist peptide and increase basal levels of tyrosine phosphorylation, which was also observed in the presence of a protein tyrosine phosphatase (PTP) inhibitor. An in vitro phosphatase assay indicated that GSE dose dependently inhibited PTP-1B and Src homology 2 domain-containing phosphatase-1 activity, which positively regulates platelet aggregation. We propose that GSEs inhibit platelet aggregation by inhibiting tyrosine phosphatase activity. Moreover, we showed that GSE ingestion inhibited platelet aggregation in mice without enhancing tail bleeding, implying that GSE supplementation might be beneficial to prevention of thrombotic diseases.

Multifunctional Chitosan Scaffold Platforms Loaded with Natural Polyphenolic Extracts for Wound Dressing Applications

“…Polymers combined with natural compounds are being increasingly explored as a viable strategy to modify intrinsic material properties and achieve the desired performance. In the field of hemostasis, CS has been shown to have outstanding performance due to its ability to interact with blood cell components. ,,,,,, Similarly, natural polyphenolic compounds such as GSE and PE have been extensively studied for their beneficial therapeutic properties. ,,, Previous studies have suggested that the negative surface charges of these extracts may facilitate material–blood interactions. ,, However, their role in hemostasis remains unclear, and conflicting results have been published in the literature. − The multifactorial nature of the coagulation process may explain these controversial results. In the present study, the synergistic effect of CS combined with GSE and PE has led to the formation of new scaffold platforms with superior biocompatibility and hemocompatibility, thus demonstrating their potential in wound dressing applications.…”

“…Polyphenolic compounds, such as Vitis vinifera grape extracts (GSE) and Pinus radiata bark extracts (PE), have emerged as promising phytotherapeutic agents in biomedicine due to their anti-inflammatory, cardioprotective, antimicrobial, and antioxidant properties. ,− For these reasons, the potential of these extracts in biomedicine is being widely explored. Although several studies have been performed in the literature using GSE for hemostatic applications, the literature entries are scattered, and the approaches lack systematics due to the conflicting results reported on the role of grape extracts in coagulation. − Moreover, to the best of the authors’ knowledge, no reports on the role of PE in coagulation have been found. This scenario allows for further investigation of the hemostatic potential of these natural extracts.…”

Antioxidant/Pro-Oxidant Actions of Polyphenols From Grapevine and Wine By-Products-Base for Complementary Therapy in Ischemic Heart Diseases

“…Many overlapping mechanisms characteristic for CVD, particularly IHD, were found to be influenced by polyphenols. Of these mechanisms, polyphenols were found to reduce myocardial oxygen consumption and/or to increase oxygen supply ( 8 , 53 ), to enhance myocardium metabolism following ischaemia/reperfusion ( 53 , 54 ), to inhibit platelet aggregation ( 51 , 55 ), thrombosis ( 55 ), to regulate lipid metabolism ( 52 ), to reduce inflammation ( 56 ), to inhibit atheromatous plaques formation ( 50 ), to promote endothelial cell repair ( 57 ), to protect remaining myocardial cells or to restore myocardial contraction ( 58 ). According to these mechanisms, polyphenols will act on multiple molecular targets involving different synergistic protective pathways.…”