• Journal of Nutrition and Health
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• 제26권5호
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• pp.513-523
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• 1993

In this experiment, we investigated the hypolipidemic and antithrombotic effects of rats fed diets with different common oils in Korea for different feeding periods(4 weeks or 12 weeks), using Korean sesame oil, perilla oil, rice bran oil and mixed oil. W-3/w-6 ratio of each group was 0.001, 1.44, 0.03 and 0.112, respectively. P/S ratio of each group was 9.64, 10.49, 5.58 and 1.68, respectively. The result were as follows: 1) According to the age, body fat accumulation was increased. 2) Perilla oil(w-3 rich) decreased total lipid, triglyceride and total cholesterol, and increased HDL/total cholesterol ratio. 3) With regard to the compositono of platelet fatty acids, Perilla oil increased w-3/w-6 ratio of the platelet. Perilla oil lengthened bleeding time and decreased MDA(MalonDAdehyde) formation which determined in place of Thromboxane A2(TXA2) in platelet. This result can suggest that linoleic acid of perrilla oil seem to supress the conversion of linoleic acid to arachidonic acid(AA 20:4, w-6) and eicosapentaenoic acid(EPA, 20:5, w-3) trannnsformed from linolenic acid to suppress the conversion of arachidonic acid to TXA2. Since TXA2 is platelet-aggregating and vasoconstricting agent, the reduction of TXA2 tgeneration by platelet with increased linolenic acid intakes shows prologed bleeding time. In conclusion, w-3 rich perilla oil has strong hypolipidemic and antithrombotic effects by changing fatty acid profiles of the platelet.

• Journal of Ginseng Research
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• 제36권1호
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• pp.40-46
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• 2012

Ginseng, the root of Panax ginseng Meyer, has been used frequently in traditional oriental medicine and is popular globally. Ginsenosides, which are the saponins in ginseng, are the major components having pharmacological and biological activities, including anti-diabetic and anti-tumor activities. In this study, we investigated the effects of total saponin from Korean red ginseng(TSKRG) on thrombin-produced thromboxane $A_2$ ($TXA_2$), an aggregating thrombogenic molecule, and its associated microsomal enzymes cyclooxygenase (COX)-1 and $TXA_2$ synthase (TXAS). Thrombin (0.5 U/mL) increased $TXA_2$ production up to 169 ng/$10^8$ platelets as compared with control (0.2 ng/$10^8$ platelets). However, TSKRG inhibited potently $TXA_2$ production to the control level in a dose-dependent manner, which was associated with the strong inhibition of COX-1 and TXAS activities in platelet microsomes having cytochrome c reductase activity. The results demonstrate TSKRG is a beneficial traditional oriental medicine in platelet-mediated thrombotic diseases via suppression of COX-1 and TXAS to inhibit production of $TXA_2$.

• 대한정형외과학회지
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• 제56권6호
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• pp.504-511
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• 2021

목적: 양측 슬관절 퇴행성 관절염으로 동시에 시행하는 양측 인공 슬관절 전치환술(simultaneous bilateral total knee arthroplasty, SBTKA)의 정맥 투여 금기에 해당하는 환자를 포함하여 관절강 내 트라넥삼산(tranexamic acid, TXA) 투여 후 배액량, 실혈량, 수혈률, 수혈량 및 합병증 발생의 차이를 비교해 보고자 하였다. 대상 및 방법: 2016년 4월부터 2018년 12월까지 퇴행성 관절염으로 SBTKA를 시행하였던 환자 중 관절낭 봉합 후 배액관을 통해 관절강 내로 한쪽당 3 g의 TXA를 주입한 139명을 실험군(group T), 2007년 10월부터 2010년 8월까지 TXA를 주입하지 않고 수술하였던 SBTKA 환자 57명(group A)을 대조군으로 설정했다. 양 군은 나이, 성별에 따른 유의한 차이는 없었다(p=0.572, 0.474). TXA는 정맥 내 투여의 금기에 해당하는 환자들에게도 관계 없이 주입하였고 염증성 관절염으로 수술을 시행한 환자는 본 연구에서 제외시켰다. 각각 평균 배액량, 실혈량, 수혈률, 수혈량과 일 평균 혈색소의 변화 추이, 일 평균 수혈량을 비교하였다. 합병증으로 심부 정맥 혈전증, 폐색전증, 감염, 뇌경색, 심근경색 발생 여부를 조사하였다. 결과: 평균 실혈량은 group A와 group T에서 각각 2195.32±1175.63 ml, 1145.09±382.95 ml, 평균 배액량은 1178.30±484.59 ml, 774.19±310.06 ml로 group T에서 각각 유의하게 적었다(p=0.002, <0.001). 수혈률은 각각 77.2% (44/57), 0.7% (1/139), 전체 평균 수혈량은 각각 735.44±550.83 ml, 4.60±54.28 ml로 group T에서 각각 유의하게 적었다(p<0.001, <0.001). 혈색소는 group A, group T에서 각각 술 후 3, 4일째 증가하였다(p<0.001, 0.001). 합병증으로 심부 정맥 혈전증이 group T에서 2예(1.4%), 폐색전증이 3예(2.2%) 발생하였으나 group A에서는 발생하지 않았다. 감염, 뇌경색, 심근경색은 모두에서 발생하지 않았다. 결론: 동시에 시행하는 SBTKA에서 TXA의 관절강 내 주입은 TXA의 평균 배액량, 실혈량, 수혈률, 수혈량을 유의하게 감소시키며 정맥 내 투여 금기에 해당하는 환자들을 포함하여도 합병증 발생률이 높아지지 않는다.

• 대한의생명과학회지
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• 제22권4호
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• pp.127-139
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• 2016

A species of the fungal genus Cordyceps has been used as an ingredient of traditional Chinese medicine. In this study, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from culture solution of Cordyceps militaris-hypha, and evaluated its antiplatelet effects on human platelet aggregation. WIB-801CE dose-dependently inhibited ADP-, collagen-, and thrombin-induced platelet aggregation. These antiplatelet effects by WIB-801CE were associated with the attenuation of thromboxane $A_2$ ($TXA_2$) production and serotonin release by ADP, collagen, and thrombin. The inhibition of $TXA_2$ production by WIB-801CE was due to the inhibition of cyclooxygenase-1, $TXA_2$ synthase, and cytosolic phospholipase $A_2$ activity. Therefore, these data suggest that WIB-801CE may be a beneficial component against protection from platelet aggregation-mediated thrombotic disease.

• Journal of Applied Biological Chemistry
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• 제63권2호
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• pp.131-136
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• 2020

When blood vessels are damaged, a fast hemostatic response should occur to minimize blood loss and maintain normal circulation. Platelet activation and aggregation are essential in this process. However, excessive platelet aggregation or abnormal platelet aggregation may be the cause of cardiovascular diseases such as thrombosis, stroke, and atherosclerosis. Therefore, finding a substance capable of regulating platelet activation and suppressing agglutination reaction is important for the prevention and treatment of cardiovascular diseases. 6,7-Dimethoxy-2H-chromen-2-one (Scoparone), found primarily in the roots of Artemisia or Scopolia plants, has been reported to have a pharmacological effect on immunosuppression and vasodilation, but studies of platelet aggregation and its mechanisms are still insufficient. This study confirmed the effect of scoparone on collagen-induced human platelet aggregation, TXA₂ production, and major regulation of intracellular granule secretion (ATP and serotonin release). In addition, the effect of scoparone on the phosphorylation of the phosphoproteins PI3K/Akt and mitogen-activated protein kinases (MAPK) involved in signal transduction in platelet aggregation was studied. As a result, scoparone significantly inhibited the phosphorylation of PI3K/Akt and MAPK, which significantly inhibited platelet aggregation through TXA₂ production and intracellular granule secretion (ATP and serotonin release). Therefore, we suggest that scoparone is an antiplatelet substance that regulates the phosphorylation of phosphoproteins such as PI3K/Akt and MAPK and is of value as a preventive and therapeutic agent for platelet-derived cardiovascular disease.

• Biomolecules & Therapeutics
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• 제22권3호
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• pp.223-231
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• 2014

In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its $IC_{50}$ value was $175{\mu}g/ml$. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated $[CA^{2+}]_i$ mobilization and thromboxane $A_2$ ($TXA_2$) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated $[CA^{2+}]_i$ level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor ($IP_3R$) phosphorylation. These results suggest that the inhibition of $[CA^{2+}]_i$ mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of $IP_3R$. CE-WIB801C suppressed $TXA_2$ production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and $TXA_2$ synthase (TXAS). These results suggest that the inhibition of $TXA_2$ production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent $CA^{2+}$-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• 대한임상검사과학회지
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• 제49권2호
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• pp.99-107
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• 2017

진균 속에 속하는 종인 Cordyceps는 중국의 전통약제로서, 그 유효성분인 cordycepin이 혈소판 응집에 관여한다는 보고가 있지만 phosphoprotein 조절에 관련된 연구는 미흡하다. 본 연구에서는, cordycepin이 fibrinogen binding에 관여한다고 알려진 PI3k/Akt와 $TXA_2$ 분비 및 과립방출에 관여한다고 알려진 p38와 같은 phosphoprotein의 인산화를 어떻게 조절하며 혈소판응집을 억제시키는지 규명하고자 하였다. 그 결과, cordycepin가 $261.1{\mu}M$의 $IC_{50}$으로 collagen이 유도한 혈소판 응집을 강력하게 억제하였고, PI3K와 Akt의 인산화를 감소시키며 ${\alpha}IIb/{\beta}_3$에 대한 fibrinogen 결합을 농도의존적으로 억제하였다. 또한, cordycepin은 collagen이 촉진시킨 p38의 인산화를 억제함으로써, 과립방출의 지표인 ATP 과 serotonin의 방출을 억제하였고 COX-1과 TXAS의 활성 및 $PLC-{\gamma}_2$ 인산화에 대한 영향없이 $TXA_2$ 생성량을 감소시켰다. 따라서, cordycepin은 PI3K/Akt, p38와 같은 phosphoprotein의 인산화를 억제함으로써 혈소판 응집억제를 나타내는 항혈전 치료 및 예방약물로서 유용한 가치가 있다고 여겨진다.

• 동의생리병리학회지
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• 제19권5호
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• pp.1391-1398
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• 2005

The anti-thrombic properties of the oriental herbal medicine Daejowhan(DJW, 大造丸) which consists of 11 kinds of herbs (indicated as ratio) of Rehmanniae Radix 24%, Hominis Placenta 5%, Testudinis Carapax 9%, Eucommiae Cortex 9%, Asparagi Radix 9%, Phellodendri Cortex 9%, Achyranthis Radix 7%, Liriopis Tuber 7%, Angelicae Sinensis Radix 7%, Ginseng Radix 5% and Schizandrae Fructus 3% were investigated. The water extracts from DJW inhibited Platelet-activating factor(PAF) induced platelet aggregation. DJW was extracted with methanol and further fractionated by ethylacetate. A 70% methanol extract showed a strong inhibition against PAF-induced aggregation in vitro and in vivo assays. The ethylacetate soluble fraction was shown to have inhibitory effect on PAF-induced platelet aggregation in vitro assay. The ethylacetate soluble fraction specially protected against the lethality of PAF, while verapamil did not afford any protection. These results indicate that the water extracts and alcoholic-fractions inhibit the action of PAF in vivo by an antagonistic effect on PAF, so that it may be useful in treating disorders caused by PAF, such as acute allergy, inflammation, asthma, gastrointestinal ulceration, toxic shock and so forth. DJW was investigated regarding its assumed anti-thrombic action on human platelets which was deduced from its ability to suppress Arachidonic acid(AA)-induced aggregation, exocytosis of ATP, and inhibition of Cyclooxygenase(COX) and Thromboxane synthase(TXS) activity. The latter two effects were estimated from the generation of Prostaglandin $E_2(PGE_2)$ and Thromboxane $A_2(TXA_2)$ respectively. Exogenously applied AA ($100{\mu}mol/{\ell}$) provoked a $89\%$ aggregation of platelets, the release of 14 pmol ATP, and the formation of either 225 pg $TXA_2$ or 45 pg $PGE_2$, each parameter being related to 106 platelets. An application of DJW 5 min before AA dose-dependently diminished aggregation, ATP-release and the synthesis of $TXA_2$ and $PGE_2$ with $IC_{50}$ values of 74, 108, 65, $72{\mu}g/m{\ell}$, respectively. The similarity of the $IC_{50}$ values suggest an inhibition of COX by DJW as primary target, thus suppressing the generation of $TXA_2$ which induces aggregation of platelets and exocytosis of ATP by its binding on $TXA_2$-receptors.

• Journal of Nutrition and Health
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• 제26권7호
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• pp.839-850
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• 1993

This study investigated the hypolipidemic and antithrombotic effects of linolenic acid derived from Korean perilla oil. The experimental rats(male, Sprague-Dawley) were divided into 5 groups using a Randomized Complete Block Design and fed one of the five following diets : DO*/O#. D4/O, D4/4, D4/8, or D4/20(D*/# represents the ratio of linoleic to linoenic acid as the percentage of total dietary energy intake) for 4 or 8 months. Bleeding time and whole blood clotting time were determined and the composition of serum and platelet lipids analyzed. Comparisons from the DO/O to the D4/20 group showed that serum lipids (total lipid, triglyceride, total cholesterol, and HDL-cholesterol) gradually decreased with increasing linolenic acid intake - the hypolipidemic effect. The composition of platelet fatty acids[the ratio of eicosapentaenoic acid(EPA)/arachidonci aci(AA)] increased gradually with increasing linolenic acid intake. Higher linolenic acid intake increased bleeding time and whole blood clotting time, and decreased malondialdehyde(MDA) production in the platelets, though no significant differences. These results suggest that linolenic acid derived from perilla oil appears to suppress the conversion of linoleic acid to AA and the EPA transformed from linolenic acid appears to suppress the conversion of AA to TXA2. Since TXA2 is a platelet-aggregating and vasoconstricting agent, the redulction of TXA2 released by platelets with increasing intake of perilla oil containing a lot of linolenic acid confers an antithrombotic effect.

• Journal of Periodontal and Implant Science
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• 제47권3호
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• pp.134-142
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• 2017

Purpose: This study aimed to evaluate the effects of a cetylpyridinium chloride (CPC) and tranexamic acid (TXA) mouth rinse on patients with gingivitis. Methods: This randomized, placebo-controlled, double-blind, parallel-group, clinical trial included 45 healthy adults with gingivitis, who were randomized into 2 groups. The experimental group used a 0.05% CPC and 0.05% TXA mouth rinse, and the control group used a placebo mouth rinse. The following clinical indices were assessed at baseline, at 3 weeks, and at 6 weeks: the Turesky-Quigley-Hein plaque index (QHI), the $L{\ddot{o}}e-Silness$ gingival index (GI), and bleeding on marginal probing (BOMP). The subjects used the mouth rinse during the experimental period for 20 seconds, 4-5 times daily (10 mL each time). Results: There were no significant differences in the clinical indices between the groups at baseline. In the experimental group (CPC+TXA), a statistically significant improvement was evident in the QHI, GI, and BOMP at 3 and 6 weeks. These results were similar to those observed in the control group at 3 and 6 weeks, although the change in BOMP was not statistically significant in that group. At 6 weeks, the experimental group had a significantly lower mean score for the QHI than the control group. Conclusions: This study demonstrated that a CPC and TXA mouth rinse exhibited significant antiplaque and anti-gingivitis efficacy, and had a positive effect on bleeding control when used daily for 6 weeks.