• 한국식품영양과학회지
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• 제31권3호
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• pp.511-515
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• 2002

최근 동물성 식품 및 지방 섭취 증가로 인한 현대인의 식생활 변화로 혈소판 활성화가 직접적 원인인 뇌심혈관질환의 사망률이 증가되고 성인병 예방과 치료의 대처방안으로 식품의 기능성에 대한 관심이 높아짐에 따라 진경, 항균, 진통, 해열, 이뇨, 지한, 진정 등의 작용을 갖는 작약(Peoniae radix)으로부터 추출, 분리.정제한 분획물에서 혈소판 응집 억제 작용이 있는 생리활성물질을 분리.동정하였다. 작약에서 methanol, ethyl acetate의 용매추출과 이러한 추출물에서 컬럼 및 HPLC로 분리.정제한 2개 물질의 화학구조를 $^1$H-과 $^{13}$C-NMR 스펙트라 분석한 결과 benzoyloxypaeoniflorin과 paeoniflorin을 확인하였고 혈소판 응집 억제작용은 benzoyl-oxypaeoniflorin이 비교적 강하게 나타내었다.

• 대한한방부인과학회지
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• 제21권1호
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• pp.117-133
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• 2008

Purpose: This study was performed to evaluate anti-thrombotic effects of Hyulbuchukeotanggamibang(HBCT). Methods: It was measured the effects which was given to blood flow rate through the regular volume of glass tube after the blood was diluted five times with ACD soulution. Antithrombotic effect was calculated as a percentage of the experimental animal figure protected from the paralysis of hind legs or death of the mouse that is caused from the administration of platelet aggregation regent. Results: 1. HBCT showed a safety in toxicity of liver. 2. In experiment of anti-thrombotic effect, HBCT inhibited the platelet aggregation induced by ADP and epinephrine, collagen, arachidonic acid as compared with the control group. 3. HBCT inhibited pulmonary embolism induced by collagen and epinephrine (inhibitory rate is 50%). 4. HBCT increased platelet number and fibrinogen amount significantly and also HBCT shortened PT and APTT significantly as compared with the control group in thrombus model induced by dextran. 5. HBCT increased blood flow rate insignificantly as compared with the control group in vivo. Conclusion: These results suggest that HBCT can be used for treating diverse female diseases caused by thrombosis.

• 대한한방부인과학회지
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• 제19권2호
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• pp.1-17
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• 2006

Purpose : The Purpose of this research was to investigate the effects of antithrombotic activities of Haenggyonghonghwatang (HGHHT). Methods : Measured the effect which was given to blood flow rate through the regular volume of glass tube after the blood was diluted five times with ACD soulution. Antithrombotic effect was calculated as a percentage of the experimental animal figure protected from the paralysis of hind legs or death of the mouse that is caused from the administration of platelet aggregation regent. Each of the groups consisted in 8 mice, was divided into Normal, Control, and HGHHT. All of these 3 group were supplied a saline solution and after an hour the control group brought the dextran extravasated blood. Also the HGHHT group was dosed to the experimental mice with Oral Zonde one day before the experiment. After that, the mice were abstained from food. And then we gave a measured amount of it before an hour. Finally, it gave rise to dextran extravasated blood as well as the Control group. Results : The results were obtained as follows. HGHHT inhibited platelet aggregation induced by ADP and epinephrine significantly as compared with the control group. HGHHT showed fibrinolytic activity insignificantly as compared with the control group. HGHHT increased blood flow rate significantly as compared with the control group in vitro, but insignificantly as compared with the control group in vivo. HGHHT inhibited pulmonary embolism induced by collagen and epinephrine(inhibitive rate 50%). HGHHT increased number of platelet, fibrinogen amount and shortened prothrombin time, activated partial thromboplastin time significantly as compared with the control group in thrombus model induced by dextran. Conclusion : HGHHT is effective antithrombotic activity from experimental result.

• Journal of Applied Biological Chemistry
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• 제62권4호
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• pp.425-431
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• 2019

Platelet activation is essential for hemostatic process on blood vessel damage. However, excessive platelet activation can cause some cardiovascular diseases including atherosclerosis, thrombosis, and myocardial infarction. Scoparone is commonly encountered in the roots of genus Artemisia or Scopolia, and has been studied for its potential pharmacological properties including immunosuppression and vasorelaxation, but antiplatelet effects of scoparone have not been reported yet. We investigated the effect of scoparone on human platelet activation prompted by an analogue of thromboxane A₂, U46619. As the results, scoparone dose-dependently increased cyclic adenosine monophosphate (cAMP) levels as well as cyclic guanosine monophosphate (cGMP) levels, both being aggregation-inhibiting molecules. In addition, scoparone strongly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), substrates of cAMP dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by scoparone resulted in inhibition of Ca²⁺ mobilization in calcium channels in a dense tubular system, and phosphorylation of VASP by scoparone led to an inability of fibrinogen being able to bind to αIIb/β3. Finally, scoparone inhibited thrombin-induced fibrin clotting, thereby reducing thrombus formation. Therefore, we suggest that scoparone has a strong antiplatelet effect and is highly probable to prevent platelet-derived vascular disease.

• 한국식품영양과학회지
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• 제35권8호
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• pp.979-984
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• 2006

과잉 철은 폐경기 여성 및 핀란드 남성에서의 심혈관계질환 증가와 예방통계학적으로 밀접한 관련이 있다고 보고되고 있다. 허혈성 심장질환, 뇌 심혈관계 질환, 암 및 노화의 원인으로 산화적 스트레스가 자유기 반응을 자극하고 지질 과산화 반응 등을 연쇄적으로 촉진시키는데 철이 위험 인자로 인식되고 있다. 그러나 뇌심혈관계 질환 유발의 중요인자인 혈소판 활성화와 관련하여 철로 인한 산화적 스트레스와 항산화작용의 연구는 부족하다고 한다. 산화적 스트레스에서 철 및 과산화수소의 자유기 형성과 관련하여 토끼 혈액에서 분리한 세정 혈소판을 사용하여 연구하였다. 산화적 스트레스를 통해 혈소판 응집을 유도하고 이에 미치는 영향을 연구한 결과에서 $H_2O_2$ 단독 투여시 혈소판 응집작용은 나타나지 않았다. $FeSO_4$ 단독 투여시 농도 의존적으로 혈소판 응집작용이 증가하여 나타내지만, $H_2O_2$ 존재 하에 $FeSO_4$ 투여시 농도 의존적으로 혈소판 응집작용이 증가되어 나타났다. 혈소판 응집을 유도하는 collagen 최적의 농도$(2\;{\mu}g/mL)$보다 낮은 1/10 농도$(2\;{\mu}g/mL)$)에서 $H_2O_2$ 및 $FeSO_4$의 영향은 농도 의존적으로 혈소판 응집작용이 증가되었다. 철 단독 투여시보다 과산화수소와 함께 투여시 농도 의존적으로 혈소판 활성화가 증대되었고 이러한 혈소판 활성화는 NAD/NADP, catalase, glutathione, mannitol, tiron 등에 의해 농도 의존적으로 억제되었고, NADH/NADPH, SOD, aspirin 등에 의해서는 영향이 없었다. 그러므로, 이러한 NAD(H)/NADP(H) cofactor는 혈소판 응집작용을 일으키는 radical을 직접 억제하기보다 radical 생성에 관련하는 것으로 사료된다. 이상의 결과에서 과잉철은 혈소판 활성화에 직접적으로 관여하고 $H_2O_2$ 존재하에 2가 철을 촉매로 하여 Fenton 반응으로 생성된 OH. 자유기가 혈소판 활성화에 중요한 역할을 한다. 그러나 혈소판에서 자유기가 arachidonic acid 대사의 활성화와 인산화 단백질로 인한 세포내 정보전달에 관한 연구가 더 이루어져야 한다고 사료된다.

• Journal of Applied Biological Chemistry
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• 제63권3호
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• pp.235-241
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• 2020

An essential component of the hemostatic process during vascular damage is platelet activation. However, many cardiovascular diseases, such as atherosclerosis, thrombosis, and myocardial infarction, can develop due to excessive platelet activation. Isoscopoletin, found primarily in plant roots of the genus Artemisia or Scopolia, has been studied to demonstrate potential pharmacological effects on Alzheimer's disease and anticancer, but its mechanisms and role in relation to thrombus formation and platelet aggregation have not yet been discovered. This research investigated the effect of isoscopoletin on collagen-induced human platelet activation. As a result, isoscopoletin strongly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in a concentration-dependent manner. In addition, isoscopoletin greatly phosphorylated inositol 1,4,5-triphosphate receptor (IP₃R) and vasodilator-stimulated phosphoprotein (VASP), known substrates of cAMP-dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by isoscopoletin induced Ca²⁺ inhibition from the dense tubular system Ca²⁺ channels, and VASP phosphorylation was involved in fibrinogen binding inhibition by inactivating αIIb/β₃ in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clot production and finally reduced thrombus formation. Therefore, this research suggests that isoscopoletin has strong antiplatelet effects and is likely to be helpful for thrombotic diseases involving platelets by acting as a prophylactic and therapeutic agent.

• 대한수의학회지
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• 제56권2호
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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.

• Toxicological Research
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• 제32권4호
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• pp.353-358
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• 2016

The generation and collection of cigarette smoke (CS) is a prerequisite for any toxicology study on smoking, especially an in vitro CS exposure study. In this study, the effects on blood and vascular function were tested with two widely used CS preparations to compare the biological effects of CS with respect to the CS preparation used. CS was prepared in the form of total particulate matter (TPM), which is CS trapped in a Cambridge filter pad, and cigarette smoke extract (CSE), which is CS trapped in phosphate-buffered saline. TPM potentiated platelet reactivity to thrombin and thus increased aggregation at a concentration of $25{\sim}100{\mu}g/mL$, whereas 2.5~10% CSE decreased platelet aggregation by thrombin. Both TPM and CSE inhibited vascular contraction by phenylephrine at $50{\sim}100{\mu}g/mL$ and 10%, respectively. TPM inhibited acetylcholine-induced vasorelaxation at $10{\sim}100{\mu}g/mL$, but CSE exhibited a minimal effect on relaxation at the concentration that affects vasoconstriction. Neither TPM nor CSE induced hemolysis of erythrocytes or influenced plasma coagulation, as assessed by prothrombin time (PT) and activated partial thromboplastin time (aPTT). Taken together, CS affects platelet activity and deteriorates vasomotor functions in vitro. However, the effect on blood and blood vessels may vary depending on the CS preparation. Therefore, the results of experiments conducted with CS preparations should be interpreted with caution.

• 대한한방부인과학회지
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• 제21권1호
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• pp.55-82
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• 2008

Purpose: In this study, we evaluated anti-inflammatory activity and anti-thrombosis effect of Manbunbang(MBB) prescribed to chronic PID patients. Methods: We studied inhibitory effect of platelet aggregation, suppression effect of GPIIb/IIIa activity and inhibitory effect of $TXB_2$ and $PGE_2$ biosynthesis which were caused by ADP, epinephrine, collagen and arachidonic acid in vitro. And suppression of pulmonary embolism, changes of related factors in dextran coagulation condition model and anti-oxidative effect of oxidative damage were studied in vivo. Results: MBB extract showed LD50 of $200\;{\mu}g/ml$ or higher in mouse lung fibroblast cells, and significantly decreased the GPT and GPT level in dextran coagulation condition model compared to the control. MBB extract showed dose-dependent inhibition effect on platelet coagulation induced by ADP, epinephrine, collagen, arachidonic acid. MBB extract showed dose-dependent inhibition effect on GPIIb/IIIa activities compared to the control. MBB extract significantly suppressed TXB2 and PGE2 biosynthesis compared to the control. MBB extract suppressed pulmonary embolism triggered by collagen and epinephrine by 37.5% compared to the control. MBB extract significantly suppressed the decrease of speed of bloodstream caused by blood coagulation in dextran coagulation condition model compared to the control. Concluson : The results strongly suggest the anti-inflammatory activity of Manbunbang through anti-thrombus. Various applications using Manbunbang on inflammatory diseases are anticipated. Anti-oxidative efficacy comparison data between the Manbunbang prescription and the drug compositions may be used as important clinical information, and further investigation of anti-oxidative activities of Chrysanthemum indicum and Rhemaniae Radix should be followed.

• 한국식품영양학회지
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• 제20권2호
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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.