• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.659-664
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• 2016

Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity.

• Biomedical Science Letters
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• v.23 no.3
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• pp.277-280
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• 2017

Elsholtzia splendens, which grows on moist soil of mountainous regions, is widely distributed at all regions of Korea, especially at Mountain Ji ri. It is categorized as a Labiatae plant which is dried aerial part. It has the following medicinal properties; removal of fever, alleviation of pain, a good antiphlogistic agent as well as antibacterial effects. However, the effects of E. splendens on thrombosis and platelet activation are not precisely understood. We performed this study to develop antithrombotic agents from oriental medicine herb extracts. E. splendens inhibited platelet aggregation induced by arachidonic acid and U46619 in a concentration dependent manner. E. splendens did not show an effect on anticoagulation as determined by prothrombin time (PT) or activated partial thromboplastin time (aPTT). We also tested the effects of E. splendens using a carotid artery thrombosis rat model induced by 35% $FeCl_3$ treatment. E. splendens significantly inhibited thrombus weight compared with the control group. These results show that E. splendens may be developed as a potential antiplatelet activity agent for treatment of cardiocerebrovascular disease and atherosclerosis.

• International Journal of Arrhythmia
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• v.17 no.1
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• pp.41-45
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• 2016

Atrial fibrillation (AF) can occur in acute coronary syndrome (ACS), which is a serious medical condition and may require the use of antiplatelet agents in addition to anticoagulants for stroke prevention. Recently, novel or non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly used for stroke prevention in patients with AF instead of traditional OACs. The duration of treatment or treatment with a stepwise approach (e.g. triple, double, or monotherapy) is determined depending on the clinical setting and the balance between the risks of ischemic stroke and bleeding. However, some concerns and controversies in the use of NOACs in patients with AF and ACS need to be addressed. Here, the current management for NOAC therapy in patients with ACS and AF will be reviewed based on recently published guidelines.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2004.05a
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• pp.233-233
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• 2004

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.2
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• pp.168-173
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• 2012

We performed this study to develop antithrombotic agents from oriental medicine herb extracts. Polygonum cuspidatum has been traditionally used as an edible medical resources for the treatment of cancer, pyodermatitis, hepatitis, cystitis, and inflammation. However, the effects of Polygonum cuspidatum on thrombosis and platelet activation are not precisely understood. The antithrombotic and antiplatelet activities of Polygonum cuspidatum were investigated by assessing the effect of a 70% ethanol extract of Polygonum cuspidatum on blood coagulation, fibrinolysis, and platelet aggregation. Polygonum cuspidatum showed effective fibrinolytic activity at 10 mg/mL. Polygonum cuspidatum also inhibited adenosine diphosphate induced platelet aggregation. Furthermore, evaluation of anticoagulant activity showed that an extract of Polygonum cuspidatum prolonged coagulation time via activated partial thromboplastin time (APTT). Our results show that Polygonum cuspidatum can be a potential candidate for antiplatelet activity as well as a fibrinolytic agent.

• Natural Product Sciences
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• v.7 no.2
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• pp.53-59
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• 2001

The possibility of Chungpesagan-tang, which has been recommended on the stroke patients with constipation in Korean traditional clinic, and its ingredients as a novel antithrombotic agent was evaluated. Most of its ingredients except Puerariae Radix exhibited in vitro antiplatelet aggregation activity. However, Puerariae Radix was significantly effective on ex vivo anti-platelet aggregation activity, whereas Angelicae Tenuissimae Radix, Raphani Semen and Angelicae Dahuricae Radix was not effective. Plasma recalcification was potently inhibited only by Puerariae Radix and Rhei Rhizoma treated with intestinal bacteria. Urokinase was also activated only by Chungpesagan-tang, Angelicae Tenuissimae Radix and Puerariae Radix treated with intestinal bacteria. Chungpesagan-tang exhibited the potent anti-thromboembolic activity activity in vitro. These results suggest that anti-thrombotic activity of Chungpesagan-tang should be activated by intestinal bacteria and may be important in the prevention of thrombosis and cardiovascular diseases, such as myocardial infraction stroke and arteriosclerosis.

• Journal of Microbiology and Biotechnology
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• v.12 no.4
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• pp.649-656
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• 2002

Fibrinolytic microorganisms were screened from 42 samples of Korean fermented food (7 kinds of Chungook-jang, 14 kinds of commercial Doen-Jang, 5 kinds of home-made Doen-jang, and 16 kinds of Jeot-gal), 15 samples of Japanese fermented food (5 kinds of home-made soybean paste, and 10 kinds of Natto), and 19 samples of Indonesian fermented food (Tempe) as well as starters of Meju (500 microflora from Korea, and 22 from China). Initially, 11 isolates with strong fibrinolytic activity were selected for further characterization. The fibrinolytic activity of the 11 isolates ranged from 89 to 199% of standard plasmin. Four strains, M5l from Korean fermented food (Meju), I 1-1, I 1-4, and I 5-1 from Indonesian fermented food (Tempe), were chosen based on the degree of activity and reproducibility, and identified as Staphylococcus sciuri, Citrobacter or Enterobacter, Enterococcus faecalis, and Bacillus subtilis, respectively. The first two isolates are pathogenic stains while the latter two are considered as GRAS (Generally Recognized As Safe). Fibrinolytic activity of E. faecalis, characterized and designated as BRCA-5, reached a maximum, when the producer was cultivated in Ml7 broth supplemented with 1.0% glucose for 5 h at 37$^{\circ}C$ with shaking at 180 rpm. Compared to commercial fibrinolytic enzymes, the cell-free culture supernatant of 5. faecaiis BRCA-5 showed stronger activity than plasmin and streptokinase, but similar degree of specific activity as nattokinase and urokinase, aud it also demonstrated anticoagulant and antiplatelet activity ex vivo. These features of E. faecalis make it an attractive agent as a biomaterial for health-promoting foods.

• Korean Journal of Veterinary Research
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• v.56 no.2
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• pp.67-74
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• 2016

Tomato extract has been shown to exert antiplatelet activity in vitro and to change platelet function ex vivo, but with limitations. In this study, antiplatelet activity of water soluble tomato concentrate (Fruitflow I) and dry water soluble tomato concentrate (Fruitflow II) was investigated using rat platelets. Aggregation was induced by collagen and adenosine diphosphate and granule-secretion, $[Ca^{2+}]_i$, thromboxane B2, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were examined. The activation of integrin ${\alpha}_{IIb}{\beta}_3$ and phosphorylation of signaling molecules, including mitogen-activated protein kinase (MAPK) and PI3K/Akt, were investigated by flow cytometry and immunoblotting, respectively. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were examined. Moreover, in vivo thrombus weight was tested by an arteriovenous shunt model. Fruitflow I and Fruitflow II significantly inhibited agonist induced platelet aggregation, adenosine triphosphate and serotonin release, $[Ca^{2+}]_i$, and thromboxane B2 concentration, while having no effect on cAMP and cGMP levels. Integrin ${\alpha}_{IIb}{\beta}_3$ activation was also significantly decreased. Moreover, both concentrates reduced phosphorylation of MAPK pathway factors such as ERK, JNK, P38, and PI3K/Akt. In vivo thrombus formation was also inhibited. Taken together, these concentrates have the potential for ethnomedicinal applications to prevent cardiovascular ailments and can be used as functional foods.

• Journal of Korean Neurosurgical Society
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• v.46 no.3
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• pp.226-231
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• 2009

Objective : We describe our clinical experiences and outcomes in patients who had thromboembolic complications occurring during endovascular treatment of intracerebral aneurysms with a review of the literature. The types of thromboembolic complications were divided and the treatment modalities for each type were described. Methods : Between August 2004 and March 2009 we performed endovascular embolization with Guglielmi detachable coils for 173 patients with 189 cerebral aneurysms, including ruptured and unruptured aneurysms at our hospital. Sixty-eight patients were males and 105 patients were females. The age of patients ranged from 22-82 years (average, 58.8 years). We retrospectively evaluated this group with regard to complication rates and outcomes. The types of thromboembolic complications were classified into the following three categories: mechanical obstruction, distal embolic stroke, and stent-induced complications, which corresponded to types I, II, and III, respectively. A comparison of the clinical results was made for each type of complication. Results : Only eight patients had a thromboembolic complication during or after a procedure (4.6%). Of the eight patients, two had a mechanical obstruction as the causative factor; the other three patients had distal embolic stroke as the causative factor. The remaining three patients had stent-induced complications. In cases of mechanical obstruction, recanalization occurred due to the use of intra-arterial thrombolytic agents in one of two patients. Nevertheless, a poor prognosis was seen. In the cases of stent-induced complications, in one of three patients in whom a thrombus developed following stent insertion, a middle cerebral artery territory infarct developed with a poor prognosis despite the use of wiring and an intra-arterial thrombolytic agent. In the cases of distal embolic stroke, all three patients achieved good results following the use of antiplatelet agents. Conclusion : Treatment for thromboemboic complications due to mechanical obstruction and stent-induced complications include antiplatelet and intra-arterial thrombolytic agents; however, this cannot guarantee a sufficient extent of effectiveness. Therefore, active treatments, such as balloon angioplasty, stent insertion, and clot extraction, are helpful.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.96-102
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• 2017

Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.