• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.917-923
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• 2002

Inhibitory mechanism of the anticoagulant polysaccharide purified from Codium fragile was investigated. The anticoagulant compounds (Cf-30-IV-4-ii, CF-30-IV) prolonged the clotting time at both activated partial thrombo-plastin time (aPTT) and thrombin time (TT). The Inhibition factor assay of instrinsic coagulation pathway in the blood showed that the anticoagulant polysaccharide (CF-30-IV-4-ii) inhibited other factors such as Ⅷ, Ⅸ, Ⅵ and Ⅷ of the coagulation cascade, which did not affect the lupus anticoagulant AB activity. In the thrombin inhibition pattern the CF-30-IV-4-ii did not directly influence the fibrine formation mediated by thrombin but af-fected the anticoagulant activity through the activation of antithrombin III. Base on these result, the anticoaglant polysaccharide (CF-30-IV-4-ii) was considered to inhibit serine pretense involved in the blood coagulation cascade through the enhancing antithrombin III activity. The residual effects of anticoagulant activity and antithrombosis were tested with ICR mice. The anticoagulant polysaccharide (CF-30-W) kept its anticoagulant activitv for 6 hrs with 100% survival at a dose of 150 mg/kg in the antithromboisis test. The anticoagulant effect of CF-30-RF in ex vivo was proportional to the concentration of intravenously injected dose up to 100 mg/kg.

• 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.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.53-78
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• 2009

Purpose: In this study, we investigated the anti-thrombotic and antiinflammatory efficacy of "Gamijoukyungtang(GJKT)". Methods: We studied inhibitory effects of platelet aggregation, FXa activation, $TXB_2$ and $PGE_2$ biosynthesis and suppressive effects of GPIIb/IIIa activity and oxidative damage, pro-inflammatory cytokine reduction effects of 'GJKT(by press extractor)/GJKT-1(by pressless extractor)' in vitro. Also, we studied suppression of pulmonary embolism, AV shunt model in rats and shortening of Rat tail bleeding time in vivo. Results: GJKT/GJKT-1 extract showed inhibitory effects on GPIIb/IIIaactivities and platelet aggregation induced by ADP, epinephrine, collagen and arachidonic acid. They suppressed biosynthesis of $PGE_2$ but GJKT-1 only supressed biosynthesis of $TXB_2$. In FXa assay, they inhibited activation of FXa. they suppressed pulmonary embolism triggered by collagen and epinephrine. In AV shunt model, they decreased the weights of AV shunt thrombus. they inhibited pro-inflammatory cytokines and decreased oxidative damages caused by DPPH. Conclusion: We confirmed the anti-thrombosis, and ant-inflammatory efficacy of 'GJKT(by press extractor)/GJKT-1(by pressless extractor)'.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.528-533
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• 2002

To evaluate the antithrombotic and antiallergic properties of rhaponticin extracted from Rhei Rhizoma, the in vitro and ex vivo inhibitory activities of rhaponticin and its metabolite, rhapontigenin, were measured. These compounds inhibited in vitro ADP- and collagen-induced platelet aggregation. Rhapontigenin was more potent, with $IC_{50}$ values of 4 and $70{\;}{\mu}g/ml$, respectively. In ex vivo ADP- and collagen-induced rat platelet aggregation, these compounds also exhibited a potent inhibitory effect. The antiplatelet aggregation effects of rhaponticin and rhapontigenin were more potent than those of aspirin. Rhapontigenin showed significant protection from death due to pulmonary thrombosis in mice. Rhapontigenin also showed the strongest inhibitory activity against $\beta-hexosaminidase$ release induced by DNP-BSA. These compounds inhibited PCA reaction in mice. Rhapontigenin intraperitoneally administered showed the strongest inhibitory activity and significantly inhibited PCA at doses of 25 and 50 mg/kg, with inhibitory activities of 48 and 85%, respectively. The inhibitory activity of orally administered rhaponticin was stronger than that of intraperitoneally administered rhaponticin. These results suggest that rhaponticin, in the rhizome of Rhei Rhizoma, is a prodrug that has extensive antiallergic and antithrombotic properties.

• Journal of Life Science
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• v.20 no.7
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• pp.1107-1112
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• 2010

In this study, the stable maintenance of bioactivity in alkaline ionized water (AIW) and antibacterial effects of AIW were evaluated to confirm benefits of AIW. As controls, purified water (PW) and tap drinking water (DW) were used. The pH and ORP (oxidation-reduction potential) of AIW, PW and DW used were 9.5 and 120 mV, 7.2 and 144 mV, and 7.3 and 564 mV, respectively. High level of minerals was observed in DW (DW>AIW>PW of mineral contents). Concentrations of $Ca^{++}$ and $Na^+$ in DW were 14.5, and 8.4 mg/l, respectively, while no $Ca^{++}$, $Mg^{++}$, $K^+$, and $Na^+$ were detected in PW. Evaluation of antioxidant activities for AIW, PW and DW showed that the waters did not act as antioxidants. However, the DPPH (1,1-diphenyl-2-picryl hydrazyl) or superoxide radical scavenging activities or reducing power of vitamin C were stably maintained in AIW and PW, though not in DW, against heat treatment ($60^{\circ}C$) or vigorous shaking (120 rpm) at $37^{\circ}C$. Similarly, after aspirin treatment at $60^{\circ}C$ for 1 hr, the antithrombosis activity in PW and AIW was 62.6% and 55.3%, while that of DW was 52.1%. Furthermore, cell growth analysis and viable cell count of Escherichia coli H7:O157 in PW, AIW and DW showed that AIW and DW, not DW, have antibacterial activities. Our results suggest that the state of water, for example pH, ORP and mineral contents of water, should be considered in medicine or food industries, and that AIW has high potential for utilization in various fields.

• Natural Product Sciences
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• v.8 no.2
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• pp.71-75
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• 2002

As apart of our continuing search for antistroke agents from the herbal medicinal resources, we examined in vitro, ex vivo and in vivo the possibility of Sunghyangjunggisan and its ingradients as a novel antithrombotic agent. In vitro ADP- and collagen-induced rat platelet aggregations were potently inhibited by Arisaematis Rhizoma, Cinnamomi Cortex and Zingiberis Rhizoma in a dose-dependent manner, but not by Sunghyangjunggisan. However, Sunghyangjunggisan significantly inhibited ex vivo rat platelet aggregation. Arisaematis Rhizoma, Atractylodis Rhizoma Alba, and Pinelliae Rhizoma also significantly inhibited ex vivo rat platelet aggregation. Sunghyangjunggisan, Alpiniae Fructus and Zingiberis Rhizoma showed significant protection from death due to pulmonary thrombosis in mice. Therefore, Sunghyangjunggisan can express the antithrombotic action, when it is orally administered.

• Microbiology and Biotechnology Letters
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• v.43 no.2
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• pp.169-174
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• 2015

Nuruk has been used as fermentation starter in the alcohol industry for some time in Korea. Various bioactivities, such as antiproliferative and anti-obesity, of R4 nuruk made from Rhizopus oryzae KSD-815 have been previously reported. In this study, the hot water and ethanol extract of R4 nuruk and their subsequent organic solvent fractions were prepared, and their antithrombosis activities were evaluated. The ethylacetate fraction showed strong anti-coagulation activity, and the ethylacetate and butanol fraction from hot water extract demonstrated platelet aggregation inhibitory activity, without hemolysis against human RBC. Our results suggest that R4 nuruk has the potential to act as a new anti-thrombosis agent.

• Journal of Life Science
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• v.24 no.8
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• pp.865-872
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• 2014

In this study, ethanol and hot water extracts of lees from Korean traditional wine (J-B, J-S, J-Y, J-H, and J-W) were prepared, and their effects on blood coagulation, platelet aggregation, and hemolysis of human red blood cells (hRBCs) were investigated to develop functional food ingredients from lees. The pH and brix of the lees ranged from 3.90 to 4.29 and 5.0 to $27.0^{\circ}$, respectively, and there was a huge difference in the water and ethanol content among the lees. The nuruk and additives used affected the color and physicochemical properties of lees. The J-W takju made from only rice and traditional nuruk, which has $13^{\circ}$ brix and 1.8% of alcohol, has potential as functional food ingredient. With regard to the extraction yields of lees, higher yields were obtained from J-H, which contains different medicinal plants, in ethanol, followed by J-W, J-B, J-S, and J-Y. Higher extraction yields of lees were obtained from J-S in hot water, followed by J-B, J-W, J-H, and J-Y, respectively. The ethanol extract of J-H and the hot water extract of J-Y had the highest contents of total polyphenol and total flavonoids among the lees extracts. The 10 lees extracts did not show hemolysis activity against hRBCs up to 5 mg/ml. In an anticoagulation activity assay, the ethanol extracts of three yakju lees (J-B, J-S, and J-Y) and the hot water extract of J-W inhibited thrombin activity, whereas the hot water extract of J-B, J-S, and J-H inhibited blood coagulation factors. In an antiplatelet aggregation activity assay, only the J-W takju lees showed significant inhibition activity. Our results suggest that lees from traditional wine had high potential as a novel antithrombosis agent.

• Korean Journal of Microbiology
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• v.43 no.4
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• pp.298-303
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• 2007

Antithrombotic activities of water extract of cheongkookjang and cheongkookjang fermented with green tea or mugwort were evaluated on some antithrombosis related activities in vitro and thrombotic death inhibition in vivo. Cheongkookjang made of white soybean (Glycine max) or black small soybean (Rhynchosia nulubilis) showed potent antioxidative activities. Addition of green tea or mugwort during cheongkookjang fermentation increased the antioxidative activity, cheongkookjang with green tea showed more drastic increase compared with cheongkookjang with mugwort. Nitrite scavenging effects of the cheongkookjang extracts were prominent but the addition of green tea or mugwort seldom increased the scavenging effects. All the cheongkookjang extracts showed strong inhibitory activities on platelet aggregation. The inhibitory activities of cheongkookjang were increased considerably by addition of green tea or mugwort even with low concentration. Plasmin unit as fibrinolytic activity was not affected considerably by addition of green tea. Addition of mugwort decreased the activity transiently at low concentration ($0.3{\sim}1.0%$) but increased again slowly at higher concentration ($1{\sim}3%$). In vitro thrombotic death inhibition test, the antithrombotic activity of cheongkookjang made of black small bean with green tea was higher by about 1.5 times compared to that without green tea. As results, cheongkookjang might inhibit antithrombosis not only by fibrinolytic action but also by inhibition of platelet aggregation and antioxidative action. The addition of functional materials such as green tea or mugwort could increase the antithrombotic function, even at low concentration.

• 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.