TY - JOUR
T1 - Grape seed extracts inhibit platelet aggregation by inhibiting protein tyrosine phosphatase
AU - Jin, Joseph Wuxun
AU - Inoue, Osamu
AU - Suzuki-Inoue, Katsue
AU - Nishikawa, Go
AU - Kawakami, Yoshinori
AU - Hisamoto, Masashi
AU - Okuda, Tohru
AU - Ozaki, Yukio
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
KW - collagen
KW - grape seed extracts
KW - platelets
KW - polyphenols
KW - protein tyrosine phosphatase
KW - protein tyrosine phosphorylation
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U2 - 10.1177/1076029613481103
DO - 10.1177/1076029613481103
M3 - Article
C2 - 23478570
AN - SCOPUS:84896821720
SN - 1076-0296
VL - 20
SP - 278
EP - 284
JO - Clinical and Applied Thrombosis/Hemostasis
JF - Clinical and Applied Thrombosis/Hemostasis
IS - 3
ER -