• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.41-49
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• 2008

Background : The central physiological derangement of hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) is a vascular dysfunction, manifested by hemorrhage, impaired vascular tone and increased vascular permeability. Platelet activating factor (PAF), whose actions are mediated through a specific receptor, is a potent bioactive lipid. PAF has diverse biological functions in the vascular system, such as increasing vascular permeability, adhesion of leukocytes to the endothelium and reduction of cardiac output, which result in hypotension and shock. The goal of the present study was to investigate whether PAF is involved in the pathogenesis of HFRS. For this purpose, we evaluated the effect of HTNV on the expression of PAF receptor (PAF-R) and on the activity of PAF-acetylhydrolase (PAF-AH) instead of PAF because PAF is rapidly degraded by PAF-AH in vivo. Materials and methods : To evaluate the expression of PAF-R, we performed reverse-transcription PCR, western blot and FACS analyses using HTNV-infected human umbilical vein endothelial cells (HUVECs) and non-infected (control) HUVECs. In addition, we measured the activity of plasma PAF-AH in HFRS patients and normal healthy persons. Results : The mRNA and protein expression of PAF-R was increased in HTNV-infected HUVECs compared with control HUVECs at 2 and 3 days post-infection (d.p.i.). FACS analysis showed that HTNV induced the surface expression of PAF-R in HUVECs from 2 d.p.i. The activity of plasma PAF-AH was 2.5-fold lower in HFRS patients than in normal healthy persons. Conclusion : Increased PAF-R expression by HTNV might increase the responsiveness to PAF in endothelial cells. Reduced PAF-AH activity in the blood of HFRS patients might delay PAF degradation. These results suggest that changes in PAF-R and PAF-AH by HTNV might influence to PAF activity and might be involved in the vascular dysfunction of HFRS.

• Proceedings of the KAIS Fall Conference
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• 2003.06a
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• pp.320-321
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• 2003

최근 천연물을 중심으로 한 학문이 발전하면서 천연물이 가지는 생리활성 물질에 대한 관심이 중대되고 있다. 또한 인공합성품의 일부가 안정성의 문제가 제기되면서 천연물의 이용분야는 더욱 확대되고 있다. 급속한 경제발전과 생활수준의 향상으로 식생활을 포함한 생활방식의 다양화로 인하여 과거 감염 위주의 질병이 감소하고 선진국형의 만성퇴행성 질환이 증가하는 추세이다. 혈소판은 혈전증(thrombosis)과 지혈증(haemstasis)에서 중요한 역할을 담당하고 있는 인자로서 현관 내 병적 이상으로 인한 과도한 혈전의 생성은 뇌 -심혈관계 질환의 중요한 유발인자로 작용하므로 뇌ㆍ심혈관계 질환이나 항고지혈증을 연구하는데 유용하게 이용되고 있다. 본 연구에서는 토끼 혈액에서 분리한 세정 혈소판 부유액을 이용하여 작약 MeOH 추출물에서 분리한 천연생리활성물질들을 대상으로 혈소판 응집억제활성에 대하여 연구하였다. 작약 MeOH 추출물의 혈소판 응집억제활성 측정에서 강한 혈소판 응집억제활성 작용을 보였다. 따라서 작약 MeOH 추출물을 크로마토그라피법을 이용하여 분리하였고, NMR을 이용한 분광학적 방법으로 지금까지의 분리한 자료와 비교ㆍ분석하였다. Monoterpene glycoside 계열의 성분들인 15개의 compound와 다수의 fraction들을 HPLC를 이용하여 분리하였으며, collagen으로 유도된 혈소판 응집억제활성측정 방법에서 뛰어난 응집억제활성을 보였다. 표준물질을 이용한 HPLC 분석과 ¹H-NMR 관련 자료의 검색을 통하여 최종적으로 compound 1b가 benzoyloxy-paeoniflorin(2.6％). compound 1d가 paeond(1.3％), compound 2c가 albiflorin(3.2％), compound 2e가 paeoniflorin(33.6％)임을 확인할 수 있었다. Compound 3a의 분석결과 benzoyloxypaeoniflorin과 구조적 유사성은 있으나 동일한 구조식으로 확인할 수 없었다. 그러나 collagen에서 응집억제활성이 90％ 이상으로 뛰어난 활성을 나타내므로 benzoyloxypaeoniflorin과 유사한 구조에서 benzoyl group이 다른 작용기로 치환되었거나 R₁ group이 다른 작용기로 치환된 형태로 추측하였다. Benzoyloxypaeoniflorin은 collagen＞thrombin＞U46616＞A.A(arachidonic acid)＞PAF의 순으로 활성을 보였다. 이는 paeoniflorin의 glycoside 5-carbon위치에 위치한 OH기 대신에 benzoyl기로 치환된 benzoyl 기가 혈소판 억제 산물로 작용한 것으로 추측했다. Paeoniflorin.은 U46619＞thrombin＞collagen＞A.A＞PAF순으로 억제를 보였다. Paeoniflorin이 collagen보다 thrombin에서 강한 억제를 보이는 것으로 Ca/sup 2＋/ chelate를 형성함으로 인해 calciu 대사를 저해하는 것으로 추축했다. Compound 3a는 U46619＞collagen＞A.A＞thrombin＞PAF순으로 억제율을 보이므로 이 화합물은 paeoniflorin의 benzoyl기에 OH기가 다른 치환기로 바뀌거나 paeoniflorin의 glycoside 5-carbon 위치의 OH기 대신에 다른 작용기로 치환된 것으로 추정하였다. 이러한 결과로 작약의 주성분인 paeoniflorin과 유사한 구조를 가진 다른 monoterpene glycoside 계열의 화합물들과 비교 분석하고 구조를 화인하고 이들 성분이 어떻게 혈소판 응집억제활성에 작용하는지를 연구하였다.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.1
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• pp.36-41
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• 2020

Objectives : Clozapine has been known to increase the possibility of developing cardio/cerebrovascular diseases, and the platelet activation has been deemed to be related to the occurrence of them. In author's previous study, we observed the increase of platelet activity with short-term clozapine administration. This study was conducted, as a follow-up study, to investigate the effect of clozapine on the platelet activity when administered continuously for long-term period of time of 1 year. Methods : The medical records of the patients with schizophrenia or schizoaffective disorder who were treated with clozapine for 1 year were retrospectively reviewed. The degree of platelet activation was assessed by measuring the mean platelet component. Results : Total of 24 patients were enrolled. 9 of them (37.5%) were male and 15 of them (62.5%) were female. In the Wilcoxon sign-ranks test, no significant change was observed between the mean platelet factor values at the beginning and at the end of one year. Conclusions : No significant changes of mean platelet activity were observed after continued administration of clozapine for 1 year. Considering the author's previous findings that observed a prominent decrease of mean platelet component after short-term clozapine administration, the result of this study suggests the possibility that the activity of the platelet may change depending on the duration of the clozapine administration.

• Korean Journal of Psychosomatic Medicine
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• v.30 no.2
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• pp.165-171
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• 2022

Objectives : This study was conducted to investigate the effect of 1-year administration of second-generation antipsychotics (SGAs) on the platelet activity in patients with schizophrenia through a retrospective review of the medical records. Methods : The mean platelet component (MPC) value was used as an index of the platelet activity. The included subjects (N=24) were the patients who were confirmed to have taken SGAs continuously for one year after the first MPC measurement had been performed. The change of MPC was verified through a paired sample t-test. Results : The result revealed that the mean MPC value was significantly decreased from 26.5±1.4 g/dL to 25.6±1.8 g/dL after 1-year administration of SGAs from the time of the first MPC measurement. Conclusions : This study suggests that 1-year administration of SGAs may be related with increased platelet activity, and that close monitoring for risks such as cerebrovascular/cardiovascular or thromboembolic diseases may be necessary during SGAs treatment in clinical practice.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.27-32
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• 1982

To investigate the relationship between platelet monoamine oxidase activity and serum levels of testosterone and estradiol in schizophrenic patient, 78 chronic patients were compared with 135 normal controls. 1) The monoamine oxidase activity of chronic schizophrenic group was lower than normal group. 2) In normal group, there was no sex difference in monoamine oxidase activity. But in chronic schizophrenic group, the monoamine oxidase activity in male was lower than female. 3) In male schizophrenic group, the serum estradiol level was lower than normal group. 4) In female schizophrenic group, the serum testosterone level was lower than normal group. The significances of relationship between platelet monoamine oxidase activity and sex hormones are discussed.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.249-249
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• 1994

PAF (Platelet-activating factor: 혈소판 활성화인자)는 1972년 Benveniste등에 의해 토끼의 호중구 배양 상청액중에서 발견되어 1979년 그 구조가 1-alkyl-2-acethyl-sn glycero-3-phosphocholine의 구조를 갖는 에테르형 인 지질임이 밝혀졌다. 그후 혈소판 이외 과립구, 단구나 macrophage, 혈관내피세포등 조직의 염증담당세포가 다양한 자극에 응하여 PAF를 생성됨이 보고되었다. PAF가 나타내는 대표적 활성으로는 혈소판, 호중구, 단구들의 활성화, 호중구의 유주 활성, 혈관투과성 항진, 혈압강하작용. 기관지 수축 등이 알려졌으며. 또한 염증, 알러지, 천식 endotoxin shock 등 여러질병에 직·간접적으로 관여함이 알려졌다. 이와같은 여러 생리 현상은 PAF의 특이적수용체를 개재하여 일어난다는 것이 밝혀졌다. 따라서 PAF의 다양한 질병의 관여가 밝혀짐으로서, PAF길항제의 개발이 활발히 진행되어왔다. 지금까지 PAF길항제의 개발은 PAF 구조 유사체. benzodiazepam유도체, thiazole유도체 등과 같은 합성품과 ginkolide, kadsurenone과 같은 천연물 유리의 것이 알려져 in vivo model에서도 그 효능이 확인되었다. 본 연구는 이와 같은 배경에서 20여 종의 생약에서 PAF 길항제를 검색하던 중 5종류의 생약에서 PAF 길항작용을 갖는 분획을 찾았기에 이에 보고한다.

• Microbiology and Biotechnology Letters
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• v.43 no.4
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• pp.373-377
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• 2015

The mature fruit of Sorbus commixta is known as magaja in Korea and is consumed in the form of tea and wine. In addition, it has been used to treat hypertension and articular neuralgia in folk medicine. In this study, the ethanol extract of magaja and its subsequent organic solvent fractions were prepared, and their in vitro anti-coagulation, and platelet aggregation inhibitory activities were evaluated. Among the fractions, the ethylacetate fraction demonstrated significant inhibition against thrombin, prothrombin, blood coagulation factors and platelet aggregation, without hemolysis activity up to 0.5 mg/ml. Our results suggest that the ethylacetate fraction of magaja has the potential to be used as a new anti-coagulation agent.

• The Journal of the Convergence on Culture Technology
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• v.6 no.2
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• pp.567-572
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• 2020

The purpose of this study was to investigate the effects of Anti-Thrombotic Activities and Cardiovascular Improvement of Fermented Garlic Extracts. The incidence of cardiovascular diseases (CVDs) is increasing rapidly in developed countries, with CVDs now representing the leading cause of morbidity and mortality. Natural products and ethnomedicines have been shown to reduce the risk of CVDs. Garlic is a medicinal plant used throughout the world for its anti-inflammatory, antioxidant, and antiplatelet activities. We hypothesized that fermented preparations of these products may possess stronger antiplatelet effects than the non-fermented forms owing to the increased bioavailability of the bioactive compounds produced during fermentation. Therefore, we compared these compounds via in vitro and ex vivo platelet aggregation assays by using standard light transmission aggregometry and ex vivo granule secretions from rat platelets. We found that fermented preparations exerted more potent and significant inhibition of platelet aggregation both in vitro and ex vivo. Likewise, ATP release from dense granules of platelets was also significantly inhibited in fermented preparation-treated rat platelets compared to that in non-fermented preparation-treated ones. We concluded that fermented preparations exerted more potent effects on platelet function both in vitro and ex vivo, possibly as a result of the increased bioavailability of active compounds produced during fermentation. We therefore suggest that fermented products may be potent therapeutics against platelet-related CVDs and can be used as antiplatelet and antithrombotic agents.

• Journal of Life Science
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• v.26 no.12
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• pp.1400-1408
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• 2016

The black currant (Ribes nigrum L.) is belong to the Grossulariaceae family, and has piquant berries, which can be eaten as raw or as processed foods, such as jams, jelly, juice and syrups. In this study, the fresh juice of black currant (FJBC) from Austria and its subsequent organic solvent fractions, such as hexane fraction, ethylacetate (EA) fraction, butanol fraction and water residue, were prepared and their in-vitro anti-oxidant, anti-coagulation and anti-platelet aggregation activities were evaluated. The FJBC and EA fraction, which has concentrated polyphenol and flavonoid, showed strong radical scavenging activities and reducing power. The $RC_{50}s$ of EA fraction against DPPH anion, ABTS cation, nitrite were 136.3, 66.2 and $115.5{\mu}g/ml$, respectively, those are 1/10, 1/16, and 1/7.7 of $RC_{50}s$ of vitamin C. In anti-coagulation assay, the FJBC, EA and butanol fraction showed significant inhibitory activities against thrombin, prothrombin and coagulation factors. Furthermore, the anti-platelet aggregation activities of EA and butanol fraction were the stronger than that of aspirin. The concentrations required for 50% platelet aggregation inhibition of aspirin, EA and butanol fraction were 0.395, 0.192 and 0.261 mg/ml, respectively. The EA and butanol fraction have no hemolysis activities up to 0.5 mg/ml against human red blood cells. The results suggest that the FJBC and its EA and butanol fraction have high potentials as novel anti-thrombosis agents. This report provides the first evidence of anti-thrombosis activity of black currant.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.28-33
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• 2004

This study was performed to examine in vitro biological activities such as antioxidative, nitrite scavenging effect, tyrosinase inhibitory effect and antithrombotic activity of a Korean traditional prescription, Nogyong-daebotang, composed of oriental medical herbs and antler, nourishing the blood, helthiness, strengthening of vital power and promotion of growth. The concentration of total phenolic compounds of the prescription sample was 151.3$\pm$2.6 mg％. The electron donating abilities (EDA) by reduction of 2.2'-diphenyl-1-picrylhydrazyl (DPPH) was 80.9%, inhibition rate of lipid peroxidation in thiocyanate method used linoleic acid was 88.1%. Nitrite scavenging effects of the sample were more than 70% at acidic pH, but it was pH dependent, showing the highest at pH 1.2 and the lowest at pH 6.0. Inhibition rate against tyrosinase of the sample was above 80%. Platelet aggregation induced by ADP (adenosine-5'-diphosphate) was inhibited up to 30% and the inhibitory effect was dependent on concentration of the sample.