title: Specific inhibiting characteristics of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine 'Chuanxiong,' on platelet thrombus formation under high shear rates.
abstract: We have investigated the effects of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine Chuanxiong, on platelet thrombus formation under flow conditions. We demonstrate herein that tetramethylpyrazine inhibits shear-induced platelet aggregation under relatively high shear rate of 10,800 s(-1) with modest inhibition of those occurring under relatively low shear rate of 1200 s(-1) by using optically modified cone-plate viscometer. We also demonstrate that platelet activation induced by shearing in the absence of exogenous platelet-activating agents such as ADP as evidenced by P-selectin surface expression and microparticle release detected by quantitative flow cytometry was also inhibited by tetramethylpyrazine. Moreover, we also demonstrate platelet thrombus formation on the collagen and von Willebrand factor (vWF) surface at high shear rates without significant influences on those occurring under relatively low shear rates. Because platelet thrombus formation occurring under high shear rates is known to be mediated by the vWF interaction with platelet receptor proteins GP Ibalpha and GP IIb/IIIa, we speculated that tetramethylpyrazine exerts antiplatelet effects by inhibiting the vWF-mediated process of platelet thrombus formation. Our findings, indicating the unique antiplatelet characteristics of tetramethylpyrazine, selectively inhibiting the platelet thrombus formation under high shear rates, provide good reasons for developing chemical analogs having biological functions similar to or more potent than those of tetramethylpyrazine as antiplatelet agents having unique biological functions.
authors.affiliation: Division of Cardiology, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Handa
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Goto
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001809:Blood Viscosity; D003094:Collagen / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D006801:Humans; D030004:Ligusticum; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D011719:Pyrazines / Q000494:pharmacology*; D013314:Stress, Mechanical; D013927:Thrombosis / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D014841:von Willebrand Factor; D003094:Collagen; C101574:chuangxiong extract; C017953:tetramethylpyrazine