The Antithrombotic Effect of Borneol Related to Its Anticoagulant Property

2008 ◽  
Vol 36 (04) ◽  
pp. 719-727 ◽  
Author(s):  
Yan-Hong Li ◽  
Xiao-Ping Sun ◽  
Yin-Qing Zhang ◽  
Ning-Sheng Wang
Keyword(s):  
Platelet Aggregation ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Thrombin Time ◽  
Inhibitory Effects ◽  
Antithrombotic Activity ◽  
Coagulation Parameters ◽  
Venous Shunt

Borneol is consumed excessively in China and Southeast Asian countries particularly in combined formula for preventing cardiovascular disease, but few studies were conducted on its effects on thrombosis. In this study, the antithrombotic and antiplatelet activities of borneol were investigated on thrombosis in vivo and on platelet aggregation ex-vivo. In addition, the coagulation parameters and influence on fibrinolytic activity were also assessed. The results showed that borneol had concentration dependent inhibitory effects on arterio-venous shunt and venous thrombosis but no effect on ADP and AA-induced platelet aggregation. Meanwhile, borneol prolonged the coagulation parameters for prothrombin time (PT) and thrombin time (TT), but did not show any fibrinolytic activity. It suggested that the antithrombotic activity of borneol and its action in combined formula for preventing cardiovascular diseases might be due to anticoagulant activity rather than antiplatelet activity.

scholarly journals Synthesis and Thrombin, Factor Xa and U46619 Inhibitory Effects of Non-amidino and Amidino N2-Thiophenecarbonyl- and N2-Tosylanthranilamides

2017 ◽  
Author(s):  
Soo Hyun Lee ◽  
Wonhwa Lee ◽  
Nguyen Thi Ha ◽  
Il Soo Um ◽  
Jong-Sup Bae ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Factor Xa ◽  
Inhibitory Effects ◽  
Human Endothelial Cells ◽  
Antithrombotic Activity ◽  
Pharmacological Targets

Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N2-thiophencarbonyl- and N2-tosyl anthranilamides 1-20 and six amidino N2-thiophencarbonyl- and N2-tosylanthranilamides 21-26 were synthesized and evaluated prothrombin time (PT) and activated partial thromboplastin time (aPTT) using human plasma at concentration 30 μg/mL in vitro. From these results, compounds 5, 9, and 21-23 were selected to study the further antithrombotic activity. The anticoagulant properties of 5, 9, and 21-23 significantly exhibited a concentration-dependent prolongation of in vitro PT and aPTT, in vivo bleeding time, and ex vivo clotting time. These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. In addition, data showed that 5, 9, and 21-23 significantly inhibited thrombin catalyzed fibrin polymerization and mouse platelet aggregation and inhibited platelet aggregation induced U46619 in vitro and ex vivo. N-(3'-Amidinophenyl)-2-((thiophen-2''-yl)carbonyl amino)benzamide (21) was most active.

Retinoic Acid Enhances Fibrinolytic Activity In-Vivo by Enhancing Tissue Type Plasminogen Activator (t-PA) Activity and Inhibits Venous Thrombosis

1993 ◽  
Vol 69 (04) ◽  
pp. 381-386 ◽  
Author(s):  
J J J van Giezen ◽  
G d I A Boon ◽  
J W C M Jansen ◽  
B N Bouma
Keyword(s):  
Retinoic Acid ◽  
Platelet Aggregation ◽  
Venous Thrombosis ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Tissue Type ◽  
Clot Lysis ◽  
Thrombin Time ◽  
Tissue Extracts

SummaryWe studied the profibrinolytic effect and the anti-thrombotic potential of retinoic acid in-vivo. Male Wistar rats were treated with retinoic acid either acutely or twice daily for a period of 5 consecutive days in a dose range of 0.01 to 3.0 mg/kg. Fibrinolytic activity was measured ex-vivo using the diluted blood clot lysis test and net t-PA activity in tissue extracts was measured in a spectrophotometric rate assay. Clot lysis was dose dependently increased by retinoic acid up to about 170% (relative to vehicle treated rats) at a dose of 3 mg/kg. No tachyphylaxis could be detected. Ex-vivo measured fibrinolytic activity after single administration of 1 mg/kg of retinoic acid peaked at 3 h after ingestion. Even after 18 h a significantly higher clot lysis rate was measured. Lysis of blood clots from vehicle and retinoic acid treated rats could be completely blocked by addition of tranexamic acid or antibodies against rat t-PA before clot formation. t-PA activity in plasma was slightly increased after retinoic acid treatment; no effects were measured on plasma PAI-1, u-PA, plasminogen, and α2-antiplasmin levels. t-PA activity in lung and kidney was marginally enhanced by retinoic acid but in heart and aortic tissue extracts t-PA activity was increased by about 50%. We confirmed this potential anti-thrombotic property in an in-vivo venous thrombosis model. A reduced clot size was observed after retinoic acid administration (35% reduction at a dose of 1 mg/kg). We could not detect any effect on ex-vivo measured platelet aggregation, bleeding time, prothrombin time, thrombin time, partial thromboplastin time or plasma fibrinogen level, indicating that there were no effects on platelet aggregation or blood coagulation. We conclude that retinoic acid enhanced fibrinolytic activity in-vivo by selectively enhancing t-PA activity and that retinoic acid is a potential anti-thrombotic agent in-vivo.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Inhibition of Fibrinolytic Activity In-Vivo by Dexamethasone Is Counterbalanced by an Inhibition of Platelet Aggregation

1992 ◽  
Vol 68 (01) ◽  
pp. 069-073 ◽  
Author(s):  
J J J van Giezen ◽  
J W C M Jansen
Keyword(s):  
Platelet Aggregation ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Dose Range ◽  
Coagulation System ◽  
Loop Model ◽  
Prothrombotic State ◽  
Inhibition Of Platelet Aggregation ◽  
Pai 1

SummaryDexamethasone decreases the fibrinolytic activity in cultured medium of several cell types by an induction of PAI-1 synthesis. As a result of this enhanced PAI-1 synthesis a prothrombotic state is expected in patients treated with dexamethasone. However, such a prothrombotic state is not reported as a major adverse effect. We have studied the effects of dexamethasone (dose range: 0.1–3.0 mg/kg) on the fibrinolytic system of rats after a 5 day pretreatment period. It appeared that dexamethasone dose dependently decreased the fibrinolytic activity (a dose of 1 mg/kg showed a reduction of about 40%). This reduced fibrinolytic activity could be functionally translated into an increased thrombus size as measured with a venous thrombosis model: thrombus size was increased by 50% with 1 mg/kg dexamethasone. No effects could be measured on the coagulation system, but it appeared that ex-vivo measured platelet aggregation was dose dependently inhibited by dexamethasone treatment. This effect resulted in-vivo in prolonged obstruction times as measured with a modified aorta-loop model. These results indicate that the expected prothrombotic state due to a diminished fibrinolytic activity caused by dexamethasone is counterbalanced by an inhibition of platelet aggregation.

scholarly journals Z-ligustilide Extracted from Radix Angelica Sinensis Decreased Platelet Aggregation Induced by ADP Ex Vivo and Arterio-venous Shunt Thrombosis In Vivo in Rats

2009 ◽  
Vol 129 (7) ◽  
pp. 855-859 ◽  
Author(s):  
Lian ZHANG ◽  
Jun-Rong DU ◽  
Jin WANG ◽  
Dong-Ke YU ◽  
Ya-Shu CHEN ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Angelica Sinensis ◽  
Shunt Thrombosis ◽  
Venous Shunt

In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate

2007 ◽  
Vol 98 (07) ◽  
pp. 155-162 ◽  
Author(s):  
Jean-Marie Stassen ◽  
Henning Priepke ◽  
Uwe Joerg Ries ◽  
Norbert Hauel ◽  
Wolfgang Wienen
Keyword(s):  
Platelet Aggregation ◽  
Rhesus Monkeys ◽  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Dabigatran Etexilate ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Orally Active

SummaryDabigatran is a reversible and selective, direct thrombin inhibitor (DTI) undergoing advanced clinical development as its orally active prodrug, dabigatran etexilate.This study set out to determine the molecular potency and anticoagulant efficacy of dabigatran and its prodrug dabigatran etexilate.This was achieved through enzyme inhibition and selectivity analyses, surface plasmon resonance studies, platelet aggregation, thrombin generation and clotting assays in vitro and ex vivo.These studies demonstrated that dabigatran selectively and reversibly inhibited human thrombin (Ki: 4.5 nM) as well as thrombin-induced platelet aggregation (IC50: 10 nM), while showing no inhibitory effect on other platelet-stimulating agents.Thrombin generation in platelet-poor plasma (PPP), measured as the endogenous thrombin potential (ETP) was inhibited concentration-dependently (IC50: 0.56 μM). Dabigatran demonstrated concentration-dependent anticoagulant effects in various species in vitro, doubling the activated partial thromboplastin time (aPTT), prothrombin time (PT) and ecarin clotting time (ECT) in human PPP at concentrations of 0.23, 0.83 and 0.18 μM, respectively. In vivo, dabigatran prolonged the aPTT dose-dependently after intravenous administration in rats (0.3, 1 and 3 mg/kg) and rhesus monkeys (0.15, 0.3 and 0.6 mg/kg). Dose- and time-dependent anticoagulant effects were observed with dabigatran etexilate administered orally to conscious rats (10, 20 and 50 mg/kg) or rhesus monkeys (1, 2.5 or 5 mg/kg), with maximum effects observed between 30 and 120 min after administration, respectively. These data suggest that dabigatran is a potent, selective thrombin inhibitor and an orally active anticoagulant as the prodrug, dabigatran etexilate.Footnote: Parts of this study were presented at the XVIII Congress of the International Society on Thrombosis and Haemostasis, Paris, July 2001. Thromb Haemost 2001; 86 (Suppl): Abstracts P755, P763.Institution where work was carried out: Boehringer Ingelheim Pharma GmbH &Co KG, 88397 Biberach, Germany.

scholarly journals Isolation and Characterization of a Heparin-Like Compound with Potent Anticoagulant and Fibrinolytic Activity from the Clam Coelomactra antiquata

Marine Drugs ◽  
2019 ◽  
Vol 18 (1) ◽  
pp. 6 ◽  
Author(s):  
ZhenXing Du ◽  
XueJing Jia ◽  
Jing Chen ◽  
SiYi Zhou ◽  
JianPing Chen ◽  
...  
Keyword(s):  
Fibrinolytic Activity ◽  
High Performance ◽  
Anticoagulant Activity ◽  
Resonance Spectroscopy ◽  
Thrombin Time ◽  
Sulfated Glycosaminoglycan ◽  
Isolation And Characterization

Heparin from mollusks with unique sulfated glycosaminoglycan exhibits strong anti-thrombotic activities. This study reports on a purified heparinoid from Coelomactra antiquata, which shows potent anticoagulant and fibrinolytic abilities. Its structure was characterized by infrared spectroscopy, high-performance liquid chromatography, and one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy. Its fibrinolytic activity was determined in vitro and in vivo. Its anticoagulant activity was determined by activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicated that clam heparinoid was a homogeneous glycosaminoglycan with a molecular weight of 30.99 kDa, mainly composed of →4)-α-IdoA2S-(1→4)-α-GlcNS3S6S (or GlcNS6S)-(1→4)-β-GlcA-(1→4)-α-GlcNS6S (or GlcNAC)-(1→. Furthermore, this heparinoid showed a highly anticoagulant titer and fibrinolytic value of 149.63 IU/mg and 1.96 IU/mg, respectively. In summary, clam heparinoid shows great potential for application in the clinic and antithrombotic drugs industry.

scholarly journals Protective effect of sulphated polysaccharide from Padina tetrastromatica (Dictyotaceae) on thromboembolism

2015 ◽  
Vol 7 ◽  
Author(s):  
Sulaiman Mohsin ◽  
R Mahadevan ◽  
A.S. Sumayya ◽  
G. Muraleedhara Kurup
Keyword(s):  
Platelet Aggregation ◽  
Marine Algae ◽  
In Vitro Models ◽  
Significant Inhibition ◽  
Inhibitory Effects ◽  
Antithrombotic Activity ◽  
Padina Tetrastromatica ◽  
Significant Prolongation

<p>Even though anti thrombotic effects have been reported with polysaccharides isolated from various marine algae of dictyotaceae, containing uronic acid as the main constituent. But a new polysaccharide was isolated from a species of marine algae from the Kerala coast with a composition different from those reported so far. The antiplatelet and antithrombotic activities of polysaccharides from <em>Padina tetrastromatica</em> were investigated on platelet aggregation in vitro and on pulmonary thrombosis in vivo. The polysaccharide fractions showed concentration dependent inhibitory effects on ADP-induced platelet aggregation. Using an <em>in vivo </em>mouse thrombotic model in which mice were challenged with an intravenous injection of collagen and epinephrine mixture, oral administration of the polysaccharide prior to the injection produced a significant inhibition of thrombotic death or paralysis. Aspirin showed a significant inhibition of thrombotic death similar to polysaccharide of higher dose. Polysaccharide fractions showed significant prolongation of mouse tail bleeding time. The present findings showed clear evidence of protection against thromboembolism and had good antithrombotic activity. Available data obtained by in vitro models suggest that there is a correlation between the sulfate content and antithrombotic activity.</p>

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