• KSBB Journal
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• v.27 no.6
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• pp.375-380
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• 2012

We previously reported that Ultra nattokinase$^{(R)}$ showed high fibrinolytic activity and revealed antithrombotic effect in rat blood plasma based on its ability to suppress collagen-induced platelet aggregation. This research was carried out to verify the clot lysing activity and blood flow enhancing effects of Ultra nattokinase$^{(R)}$ via monitoring and comparing the antithrombotic effects in rat artery between oral administration of Ultra nattokinase$^{(R)}$ and maltodextrin. SD rats were fed with 1.11 mg/kg of Ultra nattokinase$^{(R)}$ for 4 weeks. The effect on arterial thrombosis was then evaluated using an antithrombotic model after induction by $FeCl_3$. Detected fibrinolytic activity was proportional to the content of Ultra nattokinase$^{(R)}$ and statistical extents of the antithrombotic activity was enhanced strongly twice rather than control group. The PT and the aPTT, however, showed only a small difference between two groups. The results suggest that Ultra nattokinase$^{(R)}$ can effectively treat thromboembolism and enhance blood flow, and that Ultra nattokinase$^{(R)}$ can also prevent venous occlusion by aiding clot lysis.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.51 no.2
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• pp.173-178
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• 2006

Anthocyanin in blackish purple rice is composed of cyanidin, peonidin, malvidin, pelargonidin and delphinidin flavylium ion and their glucosides, which shows antioxidant activity similar to a-tocoperol. It has been demonstrated that cyanidin-3-glucoside(C3G) of anthocyanin has a high-potency antioxidant activity, and is a prominent in anticancer and antithrombotic activity. In analysis of content of anthocyanin from the genetic source of blackish purple rice, the level of C3G was approximately 80% of total contents of anthocyanins, and showed the highest content in Heugjinjubyeo, of which contains an amount of 500 mg by weight of 100g brown rice in comparison that most of varieties has less than 50mg by weight of 100g brown rice. We found that C3G pigment in blackish purple rice was considerably affected by cultural season, cultivation area, ripening temperature, and weather condition, etc. as well as genetic properties. In cross combination between Heugjinjubyeo and Suwon425, intermediate parent $F_9$ generation which was three times higher or more in C3G content than that of Heugjinjubyeo was bred, of which it contained an amount of 1678 mg by weight of 100g brown rice, and we called it 'C3GHi' Rice. And, we found that the C3GHi rice was more excellent than that of the existing Heugjinjubyeo in anticancer and antithrombotic activity. Methanol extract from Heugjinjubyeo was fractionated by organic solvents in order of n-hexane, $CH_{2}Cl_2$ and n-BuOH, and then oryzafuran, quercetin, vanillic acid and protocatechuic acid and their structures from the n-BuOH fraction were ascertained. Oryzafuran of these compounds was a natural compound found firstly in nature. Quercetin and protocatechuic acid besides new compound oryzafuran showed excellent antioxidant ability to vitamin C. These results suggest that blackish purple rice has very high value as a source of various functional food as well as staple food.

• Korean Journal of Food Science and Technology
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• v.38 no.6
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• pp.779-784
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• 2006

To produce bio-active Kochujang, 1.2% of pomegranate powder, 1.0% of hawthorn berry extract powder, 0.01% of ginko biloba extract, 1.2% of red yeast rice powder, 1.2% of silk powder, 0.2% of garlic oil, 0.2% of chitosan, 1.2% of wax gourd extract powder, and 1.0% of pine mushroom were added individually with raw materials that are needed for Kochujang process. These Kochujangs were fermented for 45 days at $30^{\circ}C$, and examined for changes in their physicochemical properties. There were no significant differences in pH, acidity, formol-N content, color and total cell count by plate count agar between Kochujangs fortified individually with functional ingredients and the control Kochujang. When 0.2% of garlic oil was added, antioxidant activity of its Kochujang product increased twice as much as that of the control Kochujang. Improved ACE inhibiting activities were observed in 1.2% of red yeast rice powder. When 1.2% of silk powder or 0.01% of ginko biloba extract were added, antithrombotic abilities were remarkably enhanced up to two times of the control Kochujang.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.823-829
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• 2002

The thrombosis importantly came to the front as the risk factor of these circulation system's disease. SilsoSanGami(SSG) was used for investigating the inhibitory effect on platelet-activating factor-induced platelet aggregation about drugs that used to improvement various symptoms created by the thrombosis in oriental medicine. In this study, the water-extracted SSG was investigated for its possible antithrombotic action on platelets. The antithrombotic activity of water-extracted SSG was deduced from its ability to suppress platelet aggregation, ATP-exocytosis, and the generation of prostaglandin E₂ and thromboxane A₂ by human platelets, stimulated with arachidonic acid. Water-extracted SSG dose-dependently suppressed the aggregation of human platelets, the release of endogenous ATP, and the formation of PGE₂ and TXB₂, both the latter usually detected to estimate the activity of COX and TXS, respectively. Since the IC/sub 50/ values necessary to inhibit COX (115 ㎍/㎖ SSG) and TXS(74 ㎍/㎖ SSG) were in the same range, inhibition of COX is suggested to be the primary target of water-extracted SSG, thus suppressing the formation of PGE₂ which is metabolized by TXS to TXA₂. We considerated that SSG has practical applicational value of clinical trial in the thrombosis caused by platelet aggregation.

• BMB Reports
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• v.29 no.6
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• pp.500-506
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• 1996

We have isolated a water-extracted novel regulator for blood coagulation from an earthworm, Lumbricus rubellus. As a folk remedy, the earthworm has been known to facilitate blood circulation. After complete heat inactivation of endogenous proteases in the earthworm, an anticoagulant(s) was purified through ammonium sulfate fractionation and three consecutive gel permeation chromatography of Sephacryl S-300, Sephadex G-75, and G-150 by measuring activated partial thromboplastin time (APTT) The anticoagulant was further purified to 2,800 fold with a C4 reversed-phase HPLC This activity was stable under heat ($100^{\circ}C$ for 30 min) and acidic conditions (0.4 N HCl). The effects of this partially purified anticoagulant on thrombin were observed with various substrates such as N${\alpha}$-benzoyl-DL-arginine-p-nitroanilide (BApNA), H-D-phenylalanyl-L-pipecoyl-L-arginine-p-nitroanilide (S-2238), N${\alpha}$-p-tosyl-L-arginine methyl ester (TAME), and fibrinogen as a natural substrate. Only TAME hydrolysis, due to an esterase activity of the enzyme, was inhibited among the chromogenic substrates. In addition, the anticoagulant not only inhibited the conversion of fibrinogen to fibrin but also prolonged the fibrin clot formation monitored with the in vitro coagulation test. Based on these observations, we suggest the significance of measuring the ability of antithrombotic drugs to inhibit the esterase activity of thrombin. In this report, it was also shown that the earthworm indeed contained a water-extractable, heat- and acid-stable anticoagulant which could be used as a novel antithrombotic agent.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.3048-3054
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• 2012

The use of aspirin is widely recommended for the prevention of heart attacks owing to its ability to inhibit platelet activation by irreversibly blocking cyclooxygenase 1. However, aspirin also affects the fibrinolytic and hemostatic pathways by mechanisms that are not well understood, causing severe hemorrhagic complications. Here, we investigated the ability of aspirin and aspirin metabolites to inhibit thrombin-activatable fibrinolysis inhibitor (TAFI), the major inhibitor of plasma fibrinolysis. TAFI is activated via proteolytic cleavage by the thrombin-thrombomodulin complex to TAFIa, a carboxypeptidase B-like enzyme. TAFIa modulates fibrinolysis by removing the C-terminal arginine and lysine residues from partially degraded fibrin, which in turn inhibits the binding of plasminogen to fibrin clots. Aspirin and its major metabolites, salicylic acid, gentisic acid, and salicyluric acid, inhibit TAFIa carboxypeptidase activity. Salicyluric acid effectively blocks activation of TAFI by thrombin-thrombomodulin; however, salicylates do not inhibit carboxypeptidase N or pancreatic carboxypeptidase B. Aspirin and other salicylates accelerated the dissolution of fibrin clots and reduced thrombus formation in an in vitro model of fibrinolysis. Inhibition of TAFI represents a novel hemostatic mechanism that contributes to aspirin's therapy-associated antithrombotic activity and hemorrhagic complications.

• The Korean Journal of Food And Nutrition
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• v.20 no.2
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• pp.114-119
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• 2007

Our research objective was to examine the in vitro biological activity of deer antler(Nogyong in Korean) extract, including the antioxidative, nitrite scavenging, and tyrosinase inhibitory effects, as well as the antithrombotic, and angiotensin I converting enzyme(ACE) inhibitory activities. The carbohydrate, protein, fat, and mineral contents of the deer antler were 7.6%, 65.3%, 3.2% and 23.9%, respectively. The electron donating ability(EDA) by the reduction of 2,2'-diphenyl-1-picrylhydrazyl(DPPH) was 67.1%, and the inhibition rate of lipid peroxidation by the thiocyanate method using linoleic acid was 92.1% in 100 mg/ml of extract. The nitrite scavenging effects were pH dependent, and were highest at pH 1.2 and lowest at pH 6.0. The sample inhibition rate against tyrosinase was above 64.0%. The platelet aggregation induced by ADP(adenosine-5'diphosphate) was inhibited up to 51.7%, and the inhibitory effect was dependent on the sample concentration. Lastly, the inhibition rate of ACE was 47.5% in 100 mg/ml of deer antler extract.

• The Journal of Korean Medicine
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• v.34 no.2
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• pp.51-58
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• 2013

Objectives: The aim of this study was to examine the antithrombotic effects of the four herbal ingredients (Mume Fructus, MF; Santali Albi Lignum, SAL; Amomi Tsao-Ko Fructus, ATF; and Amomi Fructus, AF) of modified Jeho-tang (MJHT) in a ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis model. Methods: Thirty minutes prior to a 35% $FeCl_3$ application, Sprague-Dawley (SD) rats were injected with saline, MF, SAL, ATF or AF (100 mg/kg, intraperitoneal injection), respectively. The effect of the MJHT ingredients was examined for time to occlusion (TTO) and thrombus weight (TW) in a $FeCl_3$-induced thrombosis model. Histological analysis was performed to examine the effect of the MJHT ingredients on collagen fiber damage using hematoxylin & eosin and Masson's trichrome staining. Results: Compared with vehicle treatment, MF, SAL and ATF treatment delayed TTO (vehicle, $8.11{\pm}0.60$ min; MF, $16.67{\pm}1.03$ min; SAL, $17.50{\pm}1.52$ min and ATF, $13.33{\pm}1.21$ min; P < 0.001) and inhibited thrombus formation (vehicle, $0.79{\pm}0.03$ mg/mm; MF, $0.61{\pm}0.07$ mg/mm; SAL, $0.57{\pm}0.03$ mg/mm and ATF, $0.72{\pm}0.02$ mg/mm; P < 0.001). In addition, each herbal ingredient of MJHT except for AF prevented the collagen fiber damage induced by a 35% $FeCl_3$ application. These results indicate that the MJHT ingredients MF ${\geq}$ SAL ${\geq}$ ATF ${\geq}$ AF possess antithrombotic activity in a $FeCl_3$-induced carotid arterial thrombosis. Conclusions: Altogether, these results are the first evidence that the MJHT ingredients MF, SAL and ATF have the ability to prevent vascular damage and thrombus formation in $FeCl_3$-induced carotid arterial thrombosis.