Antiplatelet and antithrombotic activities of CP201, a newly synthesized 1,4-naphthoquinone derivative.
ABSTRACT The antiplatelet and antithrombotic activities of a newly synthesized CP201, 2-(3,5-di-tert-butyl-4-hydroxyl)-3-chloro-1,4-naphthoquinone on human platelet aggregation in vitro and murine pulmonary thrombosis in vivo were examined. In addition, the antiplatelet activity of CP201 involved in calcium-signaling cascade was also investigated. CP201 showed concentration-dependent inhibitory effects on platelet aggregation induced by collagen and thrombin, with IC50 values of 4.1+/-0.3 and 4.6+/-0.4 microM, respectively. Orally administered CP201 protected mice against the collagen plus epinephrine-induced thromboembolic death in a dose-dependent manner. On the other hand, CP201 did not alter such coagulation parameters as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in human plasma in vitro. These results suggest that the antithrombotic activity of CP201 may be due to antiplatelet rather than anticoagulation activity. CP201 potently inhibited platelet aggregation challenged by calcium ionophore A23187 and thapsigargin, which is a selective inhibitor of the Ca(2+)-ATPase pump, in a concentration-dependent manner, indicating that CP201 may have an inhibitory effect on calcium-signaling cascade. This was supported by measuring [Ca2+]i in platelets loaded with fura-3AM, where CP201 inhibited the rise in cytosolic Ca2+ mediated by thrombin. Taken together, these results suggest that CP201 may be a promising antithrombotic agent, and the antithrombotic effect of CP201 may be due to antiplatelet activity, which was mediated, at least partly, by the inhibition of cytosolic calcium mobilization.
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ABSTRACT: The dissolution of carbon dioxide in water and the ensuing hydrolysis reactions are of profound importance for understanding the behavior and control of carbon in the terrestrial environment. The first X-ray absorption spectra of aqueous carbonate have been measured at three different pH values to characterize the evolution of electronic structure of carbonate, bicarbonate, carbonic acid and dissolved CO2. The corresponding carbon K-edge core-level spectra were calculated using a first-principles electronic structure approach which samples molecular dynamics trajectories. Measured and calculated spectra are in excellent agreement. Each species exhibits similar, but distinct, spectral features which are interpreted in terms of the relative C–O bond strengths, molecular configuration, and hydration strength.Chemical Physics Letters 10/2011; 514(4–6):187-195. · 2.15 Impact Factor
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ABSTRACT: In a previous work based on popular belief, Campomanesia xanthocarpa Berg., popularly known as "guavirova", showed to have a potential effect in the control of a number of conditions associated with cardiovascular diseases. The aim of the present work was to investigate the effects of C. xanthocarpa extract (CXE) on antiplatelet, antithrombotic and fibrinolytic activities in mice and in human blood. Mice were treated orally for 5 days with CXE or acetylsalicylic acid and at the end of the treatment period animals were challenged for bleeding, acute thromboembolism and ulcerogenic activity. In addition, we have assessed the prothrombin time and activated partial thromboplastin time (aPTT) after oral administration. In in vitro assays, antiplatelet effects of CXE was evaluated on platelet aggregation, and fibrinolytic activity of the extract was observed by mice or human artificial blood clot degradation. Platelet citotoxicity of the extract was also determined by the LDH assay. Results demonstrated that CXE has a significant protective effect on thrombosis. It also inhibits platelet aggregation without demonstrating cytotoxicity on platelets. CXE slightly prolonged aPTT and showed no ulcerogenic activity after oral administration. In addition, CXE showed a fibrinolytic activity. Thus, C. xanthocarpa showed antiplatelet, antithrombotic and fibrinolytic activities in mice.Evidence-based Complementary and Alternative Medicine 01/2012; 2012:954748. · 1.72 Impact Factor
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ABSTRACT: Umbilicaria esculenta as a traditional food is known to have many pharmacological activities, such as cholesterol synthesis inhibition, anti-inflammation and anti-tumor. The antithrombotic activities of UEP isolated from the lichen were examined in vitro and in vivo for the first time. The in vitro anticoagulant activity of UEP was tested by its PT, APTT and TT. The more prolongation of APTT suggested a more obvious inhibition of the intrinsic coagulation systems than the extrinsic. Its antithrombotic properties were evaluated using an arteriovenous shunt thrombosis model in rats, and its inhibition of thrombus formation increased in a dose-dependent manner. It also caused a dose-dependent increase in tail transection bleeding time. Oral administration of UEP also showed a significant dose dependent preventive effect against thrombotic death or paralysis. UEP has a potent antithrombotic effect in vitro and in vivo, which may be used as a novel, effective and promising antithrombotic agent.Carbohydrate Polymers 01/2014; 105:231–236. · 3.48 Impact Factor