• 혜화의학회지
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• 제26권1호
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• pp.19-24
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• 2017

Objectives:Spring water is widely known to relax muscles by promoting blood circulation. This study was conducted to analyze theantithrombotic effect of naturally carbonated hot spring water (NCHW) to assess its influence on blood circulation. Methods:Atopic dermatitis was induced in the skin of the mice used in this experiment. NCHW was applied, and the antithrombotic effect was assessed and compared with that of other interventions. The positive control group was treated orally with aspirin. Results:After 3 weeks of exposure to NCHW, the experimental groupshowed a significant antithrombotic effect. NCHW also produced inhibitory responses to both collagen- and ADP-induced platelet aggregation, whereas the group given aspirin reacted only to collagen-induced platelet aggregation. Conclusions:The experiment demonstrated the intrinsic antithrombotic effects of NCHW compared with those of artificially carbonated water, tap water, and aspirin. This result suggests the possibility that NCHW can be used as a supportive and alternative treatment for vascular diseases.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.402-407
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• 2023

혈소판 응집의 조절은 정상적인 지혈을 유지하는 데 중요하지만 비정상적이거나 과도한 혈소판 응집은 뇌졸중, 죽상동맥 경화증 및 혈전증과 같은 심혈관 질환에 기여할 수 있다. 따라서 혈소판 응집을 제어하거나 억제할 수 있는 물질을 식별하는 것은 이러한 상태의 예방 및 치료를 위한 유망한 접근 방식이다. Artemisia 또는 Scopolia 속 식물에서 추출한 artemisinin은 항암 및 알츠하이머병 연구와 같은 다양한 분야에서 가능성을 보여주었다. 그러나 artemisinin이 혈소판 활성화 및 혈전 형성에 영향을 미치는 구체적인 역할과 메커니즘은 아직 완전히 밝혀지지 않았다. 이 연구는 혈소판 활성화 및 혈전 형성에 대한 artemisinin의 효과를 조사하였다. 그 결과, cAMP 생성과 cAMP 의존성 kinase에 대한 기질인 VASP 및 IP₃R의 인산화가 artemisinin에 의해 유의미하게 증가되었다. IP₃R의 인산화는 조밀한 관형 시스템에서 정상적으로 동원되는 Ca²⁺를 억제하였고, VASP의 인산화는 αIIb/β₃ 혈소판 막 불활성화를 통한 fibrinogen 결합을 억제하였다. 마지막으로, artemisinin은 thrombin이 유발하는 혈전 형성을 농도의존적으로 억제하였다. 따라서 우리는 artemisinin이 혈소판 활성화의 효과적인 예방 및 치료제로 작용하여 비정상적인 혈소판 응집 및 혈전 형성으로 인해 유발되는 심혈관 질환의 개선에 기여할 수 있음을 제안한다.

• Journal of Ginseng Research
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• 제32권2호
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• pp.107-113
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• 2008

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and $Ca^{2+}$-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase $C_{\beta}$ via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate $(PIP_2)$ was hydrolyzed after 10 sec of the thrombin-stimulation, and both the phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol (PI) were brokendown after 30 sec of the thrombin-stimulation. However, PT inhibited the thrombin-stimulated hydrolysis of $PIP_2$, PIP, and PI. On the other hand, thrombin increased the level of phosphatidic acid (PA) which is phosphorylated from diacylglycerol (DG) generated by PIS-hydrolysis. However, Pr inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free $Ca^{2+}([Ca^{2+}])_i$) up to 72% as compared with control $(30.8{\pm}0.9 nM)$ in intact platelet. However, PT (100 ${\mu}g/ml$) inhibited the thrombin-elevated $[Ca^{2+}]_i$ to 100%. These results suggest that PT may have a beneficial effect on platelet aggregation-mediated thrombotic disease by inhibiting thrombin-induced platelet aggregation via suppression of the $[Ca^{2+}]_i$ level and PIS breakdown.

• 대한의생명과학회지
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• 제23권3호
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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.

• Archives of Pharmacal Research
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• 제20권6호
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• pp.539-544
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• 1997

Anti-metastatic activities of IH901, an intestinal bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo. Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT 1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

• 동의생리병리학회지
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• 제17권4호
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• pp.930-938
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• 2003

The purpose of the present study was to investigate the effects of Hyunhosaiksan (HHS) on antithrombotic actions which include blood activation, thrombus removal, warming of circulating blood, and the control of pain on abdomen and lower and upper burning spaces. HHS significantly inhibited platelet aggregation induced by ADP and epinephrine in a HHS dose-dependent manner when analyzed by the Sigmoid Emax model in WinNonlin. EC50 values of HHS were 1.71 ㎍/ml and 0.004 ㎍/ml for ADP and epinephrine respectively. In the vivo study, HHS inhibited pulmonary embolism induced by collagen and epinephrine, which was however statistically insignificant. HHS increased number of platelets, APTT and volume of fibrinogen significantly as compared with the control group in dextran-induced thrombus model. Furthermore, HHS stimulated levels of blood flow in vivo though its effect was not observed in vitro. These results suggest that Hyunhosaiksan (HHS) can be used for treating numerous diseases related with blood aggregation and circulation problems. Further systematic investigations on the synergic effects among drugs used in the oriental medicine as well as in the western medicine in relation to thrombosis therapy would provide an important insight into the potential therapeutic applications.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.528-533
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• 2002

To evaluate the antithrombotic and antiallergic properties of rhaponticin extracted from Rhei Rhizoma, the in vitro and ex vivo inhibitory activities of rhaponticin and its metabolite, rhapontigenin, were measured. These compounds inhibited in vitro ADP- and collagen-induced platelet aggregation. Rhapontigenin was more potent, with $IC_{50}$ values of 4 and $70{\;}{\mu}g/ml$, respectively. In ex vivo ADP- and collagen-induced rat platelet aggregation, these compounds also exhibited a potent inhibitory effect. The antiplatelet aggregation effects of rhaponticin and rhapontigenin were more potent than those of aspirin. Rhapontigenin showed significant protection from death due to pulmonary thrombosis in mice. Rhapontigenin also showed the strongest inhibitory activity against $\beta-hexosaminidase$ release induced by DNP-BSA. These compounds inhibited PCA reaction in mice. Rhapontigenin intraperitoneally administered showed the strongest inhibitory activity and significantly inhibited PCA at doses of 25 and 50 mg/kg, with inhibitory activities of 48 and 85%, respectively. The inhibitory activity of orally administered rhaponticin was stronger than that of intraperitoneally administered rhaponticin. These results suggest that rhaponticin, in the rhizome of Rhei Rhizoma, is a prodrug that has extensive antiallergic and antithrombotic properties.

• Natural Product Sciences
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• 제8권4호
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• pp.147-151
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• 2002

In the course of our work on anti-platelet constituents from plants, eight phenolic compounds, $({\pm})-syringaresinol$ (1), 4-hydroxybenzaldehyde (2), 4-hydroxybenzoic acid (3), vanillic acid (4), 4-hydroxy cinnamic acid (5), quercetin 3-O-rhamnoside (6), rutin (7), and quercetin $3-(2^G-rhamnosylrutinoside)$ (8) were isolated from the methanol extract of the leaves of Magnolia obovata. The compounds were identified based on the spectroscopic data. Compound 2, 3, 5, 6, 7 and 8 were isolated for the first time from genus Magnolia. 1 and 6 showed same order of inhibitory potencies as acetylsalicylic acid (ASA) to rat platelet aggregation induced by all the stimulators tested. The remaining six compounds showed only mild effects.

• Journal of Ginseng Research
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• 제40권4호
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• pp.359-365
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• 2016

Background: Glycoprotein IIb/IIIa (${\alpha}aIIb/{\beta}_3$) is involved in platelet adhesion, and triggers a series of intracellular signaling cascades, leading to platelet shape change, granule secretion, and clot retraction. In this study, we evaluated the effect of ginsenoside Ro (G-Ro) on the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$. Methods: We investigated the effect of G-Ro on regulation of signaling molecules affecting the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$, and its final reaction, clot retraction. Results: We found that G-Ro dose-dependently inhibited thrombin-induced platelet aggregation and attenuated the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$ by phosphorylating cyclic adenosine monophosphate (cAMP)-dependently vasodilator-stimulated phosphoprotein (VASP; $Ser^{157}$). In addition, G-Ro strongly abrogated the clot retraction reflecting the intensification of thrombus. Conclusion: We demonstrate that G-Ro is a beneficial novel compound inhibiting ${\alpha}aIIb/{\beta}_3$-mediated fibrinogen binding, and may prevent platelet aggregation-mediated thrombotic disease.

• 대한한방내과학회지
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• 제21권5호
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• pp.829-837
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• 2000

Purpose : To investigate the inhibitory effect of BHE on platelet aggregation and erythrocyte deformability, we performed following experiments. Methods : Concentrated Boyanghwanotang (BHE) was fed to rats for 10days. High dose group was treated with $500{\beta}{\partial}/kg$ and low dose group with $500{\beta}{\partial}/kg$. Results : BHE enhanced the blood filtration rate, reduced the platelet aggregability, inhibited granule release from collagen-stimulated platelet, the prostaglandin syn-thesis in platelet and enhanced erythrocyte deformability. Conclusion : BHE should inhibit thrombos formation due to platlete hyperaggregabili-ty and reduction of erythrocyte deformabi-lity.