RESUMO
The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its antiplatelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with IC50 values of 620 +/- 12, 823 +/- 22, 722 + 21 and 650 +/- 14 microg/mL, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.
Assuntos
Fibrinolíticos/farmacologia , Ginsenosídeos/farmacologia , Panax/química , Inibidores da Agregação Plaquetária/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/antagonistas & inibidores , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/toxicidade , Difosfato de Adenosina/antagonistas & inibidores , Difosfato de Adenosina/toxicidade , Administração Oral , Animais , Ácido Araquidônico/antagonistas & inibidores , Ácido Araquidônico/toxicidade , Testes de Coagulação Sanguínea , Carboximetilcelulose Sódica/química , Lesões das Artérias Carótidas/complicações , Trombose das Artérias Carótidas/etiologia , Trombose das Artérias Carótidas/prevenção & controle , Colágeno/antagonistas & inibidores , Colágeno/toxicidade , Relação Dose-Resposta a Droga , Fibrinolíticos/química , Ginsenosídeos/administração & dosagem , Ginsenosídeos/química , Coreia (Geográfico) , Masculino , Tempo de Tromboplastina Parcial , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Tempo de Protrombina , Coelhos , Ratos , Ratos Sprague-DawleyRESUMO
In this study, tetramethylpyrazine (TMPZ) was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 40 and 80 microg/g. In addition, intravenous injection of TMPZ (10 microg/g) significantly prolonged the bleeding time by approximately 1.5-fold compared with normal saline in severed mesenteric arteries of rats. Continuous infusion of TMPZ (1 microg/g per min) for 10 minutes also significantly increased the bleeding time approximately 1.6-fold, and the bleeding time returned to baseline within 60 minutes after cessation of TMPZ infusion. On the other hand, platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pre-treated intravenously with fluorescein sodium (10 microg/kg). When it was intravenously injected, TMPZ (250 microg/g) significantly prolonged the latent period of the induction of platelet plug formation in mesenteric venules. TMPZ (250 microg/g) prolonged occlusion time approximately 1.4-fold (183 +/- 18 seconds) compared with that of normal saline (132 +/- 14 seconds). Furthermore, aspirin (300 microg/g) showed similar activity in the prolongation of occlusion time in this experiment. In conclusion, these results suggest that TMPZ has effective antithrombotic activity in vivo and may be a potential therapeutic agent for arterial thrombosis but must be assessed further for toxicity.
Assuntos
Fibrinolíticos/uso terapêutico , Veias Mesentéricas , Inibidores da Agregação Plaquetária/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Pirazinas/uso terapêutico , Terapia Trombolítica , Trombose Venosa/tratamento farmacológico , Doença Aguda , Difosfato de Adenosina/toxicidade , Animais , Aspirina/uso terapêutico , Tempo de Sangramento , Pressão Sanguínea/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/farmacologia , Injeções Intravenosas , Artérias Mesentéricas , Veias Mesentéricas/efeitos da radiação , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacologia , Embolia Pulmonar/induzido quimicamente , Pirazinas/administração & dosagem , Pirazinas/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Reprodutibilidade dos Testes , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Trombose Venosa/etiologiaRESUMO
These experiments continued our line of inquiry into low-toxicity high-effectiveness radiomodifying agents obtained by binding radioprotective substances to biogenic and biologically active components or antidotes. Testes for toxicity and radioprotective effects were three preparations combining within one molecule AET and an adenyl nucleotide (AMP, ADP, or ATP). Ionic-bond formation was shown to have advantages over concomitant administration of AET and adenosine phosphoric acids as mixtures. The evidence obtained supports the rational foundation of the concept being developed by our laboratory.