• Journal of Life Science
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• v.20 no.6
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• pp.922-928
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• 2010

This study was carried out to develop safe and novel anticoagulation agents from oriental medicinal herbs. From 33 medicinal herbs, 40 different ethanol extracts were prepared according to place of origin or extraction parts, and anticoagulation activities were evaluated by determination of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (aPTT). The average water content and average extraction ratio for the medicinal herbs were $6.85{\pm}2.26%$ and $5.27{\pm}4.25%$, respectively. Evaluation of TT at various concentrations of the extract led to the selection of Mucuna birdwoodiana, Prunus armeniaca, Cacalia ainsliaeiflora, Cinnamonum aromaticum, and Rhus javanica Linneas potent antithrombosis medicinal herbs. Evaluation of PT and aPTT showed that the extracts of R.javanica Linne, M. birdwoodiana, and P. armeniaca have strong anticoagulation activities. Determination of hemolytic activities of 40 different ethanol extracts against human red blood cells, however, showed that only M. birdwoodiana, C. ainsliaeiflora, C. aromaticum, and R. javanica Linnehas strong anticoagulation activity without hemolytic activity at a concentration of 500 mg/ml. Our results suggest that oriental medicinal herbs, which are under a mass-production system, have potentialas a safe and novel source of anticoagulants, as well being a thrombin-specific and coagulation factor-specific inhibitor.

• Journal of Life Science
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• v.20 no.11
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• pp.1640-1647
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• 2010

Seaweeds have been recognized as a health food, having anti-obesity, anti-constipation and anticoagulation activities, and the use of seaweeds in the food, medicine, and cosmetic industries have recently significantly increased. In this study, methanol extracts were prepared from 35 different seaweeds (17 phaeophyta, 11 rhodophyta and 7 chlorophyta), and thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (aPTT) were determined in order to develop safe and novel anticoagulation agents from natural products. In TT experiments, Ecklonia cava, Ecklonia stolonifera, Eisenia bicyclis (Kjellman) Setchell, Ishige foliacea, I. okamurai, Sargassum confusum and S. yamade showed strong thrombin inhibition activity among the 35 different seaweeds. In PT experiments, the inhibitions of prothrombin were identified in the selected seaweeds from TT experiment, with the exception of S. yamade. In aPTT experiments, the seaweeds with blood coagulation inhibition factors were E. cava, E. stolonifera, E. bicyclis (Kjellman) Setchell, I. foliacea, I. okamurai, S. confusum and Hixikia fusiforme Okamura. Further anticoagulation assay with the selected 8 seaweeds suggested that S. confusum is most effective in antithrombosis, and E. stolonifera, E. bicyclis (Kjellman) Setchell, and I. foliacea have high potential as antithrombosis agents. Based on components-activity correlation analysis, flavonoids are considered as active anticoagulation components of seaweeds These results suggest that edible seaweeds, especially S. confusum, have potential as safe and novel anticoagulants, and S. yamade and H. fusiforme Okamura could be used as a thrombin-specific and coagulation factor-specific inhibitors.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.373-379
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• 2009

This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.

• BMB Reports
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• v.45 no.4
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• pp.221-226
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• 2012

Curcumin, a polyphenol responsible for the yellow color of the curry spice turmeric, possesses antiinflammatory, antiproliferative and antiangiogenic activities. However, anticoagulant activities of curcumin have not been studied. Here, the anticoagulant properties of curcumin and its derivative (bisdemethoxycurcumin, BDMC) were determined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT) as well as cell-based thrombin and activated factor X (FXa) generation activities. Data showed that curcumin and BDMC prolonged aPTT and PT significantly and inhibited thrombin and FXa activities. They inhibited the generation of thrombin or FXa. In accordance with these anticoagulant activities, curcumin and BDMC showed anticoagulant effect in vivo. Surprisingly, these anticoagulant effects of curcumin were better than those of BDMC indicating that methoxy group in curcumin positively regulated anticoagulant function of curcumin. Therefore, these results suggest that curcumin and BDMC possess antithrombotic activities and daily consumption of the curry spice turmeric might help maintain anticoagulant status.

• Journal of Korean Neurosurgical Society
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• v.42 no.5
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• pp.377-381
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• 2007

Objective : High-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than does low-molecular-weight HES. We compared the effects of low- and high-molecular-weight HES for the treatment of vasospasm and investigated the dose relationship with each other. Methods : Retrospectively, in a series of consecutive 102 patients with subarachnoid hemorrhage (SAH), 35 patients developed clinical symptoms of vasospasm of these fourteen patients were treated with low-molecular weight HES for volume expansion while the other 21 received high-molecular-weight HES as continuous intravenous infusion. Prothrombin time (PT), partial thromboplastin time (PIT), fibrinogen level, and platelet count were all measured prior to initiation, during treatment and after termination of therapy for symptomatic vasospasm. The total dose of HES ranged from 5 L to 14 L and median infusion duration was 10 days. Results : A more pronounced PTT prolongation was observed in high-molecular-weight HES group compared with low-molecular-weight HES group. No other coagulation parameters were altered. Dosage (=duration) shows a positive correlation with PTT. Clinically, significant bleeding episodes were noted in four patients who received high-molecular-weight HES. Conclusion : Coagulopathy was developed in direct proportion to molecular weight of starch and dosages. We propose the extreme caution in the administration of HES solution for the vasospasm treatment.

• Journal of Life Science
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• v.17 no.4 s.84
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• pp.535-539
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• 2007

The fructus of Crataegus pinnatifida Bunge has been used as medicinal and food source in worldwide. In this study, a strong direct thrombin inhibition and antithrombosis activity were identified from the methanol extract of C. pinnatifida Bunge fructus. The solvent fractionation of fructus extract using hexane, ethylacetate, butanol revealed that the butanol fraction has a prominent antithrombin activity. Thrombin time(blood-clot formation time) and activated partial thromboplastin time(aPTT) extended to 835% and 315% by addition of the butanol fraction at concentration of 1.25 mg/mL, whereas thrombin time extended to 287% by addition of aspirin at concentration of 1,25 mg/mL. The butanol fraction showed anthrone-positive and weak ninhydrine-postive reaction. The thrombin inhibitory activity was not related to previously reported flavonoids or polyphenols. The activity was maintained against acid treatment(0.5 N HCl for 120 min), but rapidly lost by heat-treatment($100^{\circ}C$ for 30 min). Our results suggested that fructus of C. pinnatifida Bunge with non-heat treatment process could be developed as a natural source of antithrombosis.

• The Korea Journal of Herbology
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• v.26 no.4
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• pp.125-132
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• 2011

Objectives : An aim of study is to investigate effects of curculiginis rhizoma in vitro (factor Xa (FXa) inhibitor assay, prothrombinase assay, prothrombin time (PT) assay, activated partial thromboplastin time (aPTT) assay) and in vivo experiment (blood clotting time, thromboxane B2 content assay in serum and weight of thrombus by AV-shunt rat model). Methods : We gained a human serum and used serum in vitro study such as factor X activity (FXa) inhibition, prothrombinase inhibition, prothrombin time (PT) and activated partial thromboplastin time. Fifteen SD rats were divided into three groups (intact control group and two experimental group treated with extract of Curculiginis Rhizoma(ECR)). Rats were orally administrated DW (intact control group), 600 mg/kg concertration of ECR and 200 mg/kg concertration of ECR. After one hour, we anesthetized rats and made arteriovenous (AV) shunt rat models to study weights of thrombus, took a hole blood to study content of thromboxane B2 and blood clotting time. Results : In vitro, ECR increased a inhibitory activity of FXa, prothrombinase and aPTT compared than intact control group. Especially ECR made significant increase of FXa and prothrombinase inhibitory activity (p<0.05, p<0.01). And PT were increased in ECR control group compared with intact control group. In vivo, a blood clotting time of experiment group treated with ECR 600 mg/kg were significantly increased compared with that of intact control group (p<0.05) and content of thromboxane B2 was significantly decreased in group treated with ECR 600 mg/kg in seum. The weight of thrombus were significantly reduced in group treated with ECR 600 mg/kg compared with intact control group (p<0.05). But in vivo experiment study, those of group treated with ECR 200 mg/kg were reduced compared with those of intact control group without statistical significance. Conclusions : ECR has a antithromboic activity in internal course with inhibitory activity of FXa and prothrombinase in vitro, it required to research more study for effective compounds.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1174-1180
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• 2006

The present study was sought to clarify whether the combination of mental activity with subway noise affects hematological variables. Fifty-six healthy volunteers participated in this experiment and underwent a stress task consisting of combination_of mental activity (mental arithmetic) with subway noise for 50 min and 60min of recovery after the end of the stress task. Venous blood samples were collected for measuring CBC, prothrombin time (PT), activated partial thromboplastin time (aPTT), erythrocyte sedimentation rate (ESR), fibrinogen concentration, D-dimer and high sensitive C-reactive protein (H-CRP) levels before (baseline), 50min of stress task (S-50m), and 60 min of recovery (R-60m). Total leukocyte, neutrophil and lymphocyte counts significantly increased at R-60m compared with baselines. RBC count at S-50m was higher, while monocyte counts at S-50m and R-60m were lower than those of baselines. aPTTs shortened at S-50m and R-60m, but PT reduced at R-60m as compared with baselines. D-dimer and H-CRP levels at S-50m and R-60m were significantly higher than those of baselines. These findings imply that a combination of mental activity with subway noise nay cause leukocytosis, homo-concentration, shortened PT and aPTT, decreased ESR, and raised D-dimer and H-CRP levels, suggesting possible development of inflammation and prothrombogenic reaction attributable to a subway environment.

• Korean Journal of Pharmacognosy
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• v.35 no.1 s.136
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• pp.52-61
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• 2004

Inhibitory activities of 264 methanol extracts, which were prepared from different parts of 210 kinds of wild and medicinal plants, against human thrombin were evaluated. Based on the anti-coagulation activity determined by thrombin time and activated partial thromboplastin time, the 14 extracts were screened. The fibrinolytic activity, heat stability and inhibition of other proteolytic digestive enzymes, such as pepsin, papain, trypsin and chymotrypsin, of the 14 extracts were further determined, and Ginko biloba (herba), Ephedra sinica (radix), Reynoutria elliptica (herba), Amomum tsao-ko Crevost (fructus), and Magnolia officinalis Rehd. et Wils (bark) were finally selected as possible plant sources for anti-thrombosis agent. These results suggested that medicinal and wild plants could be the potential source of thrombin inhibitor.

• BMB Reports
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• v.47 no.7
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• pp.376-381
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• 2014

Enzymatic oxidation of pyrogallol was efficiently transformed to an oxidative product, purpurogallin (PPG). Here, the anticoagulant activities of PPG were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin and activated factor X (FXa). And, the effects of PPG on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated in tumor necrosis factor (TNF)-${\alpha}$ activated human umbilical vein endothelial cells (HUVECs). Treatment with PPG resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, as well as inhibited production of thrombin and FXa in HUVECs. In addition, PPG inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. PPG also elicited anticoagulant effects in mice. In addition, treatment with PPG resulted in significant reduction of the PAI-1 to t-PA ratio. Collectively, PPG possesses antithrombotic activities and offers a basis for development of a novel anticoagulant.