• 동의생리병리학회지
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• 제16권6호
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• pp.1277-1283
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• 2002

Silsosangami(SSG) is a formula of treaditional korean medicines as an effective biological response modifier for augmenting host homeostasis of body circulation. Little is known of the biological activity of SSG and previous studies have focused mainly on their anti-thrombosis8). There is a growing interest in the pharmacological potential of the SSG due to the recent finding by our group that SSG and each constituent herbs of SSG were able to inhibit NO and prostaglandin E2 (PGE2) synthesis in murine peritoneal macrophages stimulated with bacterial endotoxin. In this paper, the effects of SSG on platelet aggregation and hemolysis in human blood were studied. SSG provoked remarkable inhibiting effect on platelet aggregation, and APTT were sensitive to the presence of this SSG. Using an in vitro system, APTT was delayed with the increment of the concentrations of these seven compounds. These results suggested that SSG might be used as a novel antithrombotic therapeutic agents in post-myocardial infarction. A SSG reduced NO production in mouse peritoneal macrophages stimulated with lipopolysaccharide, without the influence on the activity of iNOS being observed. SSG significantly reduced mouse paw edema induced by carrageenan. Western blot analysis showed that SSG reduced the expression of iNOS. The results indicate that SSG exerts anti-inflammatory effects related to the inhibition of NO production, which could be due to a decreased expression of iNOS.

• Journal of Acupuncture Research
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• 제24권2호
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• pp.31-38
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• 2007

목적 : 백자인에서 추출된 Carvacrol이 혈소판 활성화와 혈액 응고에 미치는 영향에 대해 알아보고자 하였다. 방법 : Carvacrol의 항혈소판 효과의 기제를 밝히기 위해 토끼 혈소판으로 Arachidonic Acid 유리，TXB2, PGD2, 12-HETE의생성을 방사선 크로마토그래피 분석을 사용하여 측정하였다. 결과 : 1. U46619를 제외하고 Collagen과 AA에 의해 유발된 응고는 Carvacrol 농도에 따라 억제되었다. 2. Collagen으로 인하여 자극된 AA 유리에 대한 Carvacrol의 유의한 억제 효과는 나타나지 않았다. 3. AA로 유발된 TXB2, PGD2와 12-HETE의 생성억제에 대한 실험에서 Carvacrol은 유의한 억제가 있는 것으로 나타났으며，농도의존적으로 억제되었다. 결론 : Carvacrol은 항혈소판 작용이 있는 것으로 볼 수 있다. 이는 한의학에서 활혈거어 작용으로 해석될수 있으며，타박상，윌경곤란증，탈모증 등 어혈질환의 예방 및 치료와 관련된 약침개발에 기초가 될수 있을 것으로 사료된다.

• 동의생리병리학회지
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• 제20권2호
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• pp.460-466
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• 2006

We wondered whether the mechanisms of antiplatelet aggregation of DJS-WE were through multiple pathways. Danggijakyak-san(DJS) consisting of 6 herbes of Paeoniae Radix, Poria Cocos, Angelicae Sinensis Radix, Cnidii Rhizoma, Atractylodis Macrocephalae Rhizoma and Alismatis Rhizoma, is a crude mixture of a commonly used Korean herbal medicine. The water extract (DJS-WE) of DJS has been known to have an anti-platelet aggregation activity. We have reported that DJS-WE inhibited ADP-induced aggregation as well as arachidonic acid-induced aggregation of human platelet. Clinical studies on the cardiovascular effects of DJS-WE have been done in Korea. The DJS has been used as a remedy for gastrointestinal disorders (abdominal pain, dysentery), headache, amenorrhea, and postpartum hemorrhage. It has also been claimed to have a remarkable central stimulant effect, a transient hypertensive effect, and positive inotropic and chronotropic effects. In this paper, we evaluated the possible mechanisms of the antiplatelet activity of DJS-WE using human platelets. On the other hand, the role of DJS-ethanol extract on the inhibition of platelet aggregation and hemolytic effect have not yet been investigated in detail. We also used the method of activated partial thromboplastin times (APTT) for the first time to study the inhibition on platelet aggregation activity of DJS-ethanol extract. The effect of DJS-WE on hemolysis was also investigated. DJS-WE showed a high hemolysis ability on human blood.

• 대한의생명과학회지
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• 제16권4호
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• pp.377-380
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• 2010

In this study, we investigated the effect of egg yolk lipids (EYL) on collagen ($10\;{\mu}g/ml$)-stimulated platelet aggregation in vivo. Dietary EYL significantly inhibited collagen-induced platelet aggregation, in addition, increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonist as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that EYL inhibits the collagen-induced platelet aggregation by up-regulating the cAMP and cGMP production. On the other hands, prothrombin time (PT) on extrinsic pathway of blood coagulation was potently prolonged by dietary EYL in vivo. These findings suggest that EYL prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that EYL may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

• 대한본초학회지
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• 제31권3호
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• pp.13-22
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• 2016

Objectives： Arachidonic acid is control the thromboxane A2 (TXA2) and prostacycline (PGI2) synthesis, TXA2 increase lead to thrombus produced by induces platelet aggregation and vasoconstriction. Angelicae gigantis radix (RAR) is mainly used blood deficiency and stagnation. In previous studies, RAR has been reported that a vasodilating and blood clotting delay effects. In this study, investigate that anti-oxidant and anti-thrombotic effects of RAR by heat-process.Methods： The heated angelicae gigantis radix sample were made by 140, 180, and 220 ℃ and 4, 6, 9 and 12 min using water or 30% ethanol. The anti-oxidant effects were measured by total polyphenol, total flavonoid, DPPH and ABTS radical scavening activation. Anti-thrombotic effect conducted in samples that are determined to be effective through the anti-oxidant experiment such as angelicae gigantis radix roasted 180℃, and 220℃ and angelicae gigantis radix roasted with 30% ethanol 180℃, and 220℃.Results： Anti-oxidant parameters were efficacious in high temperature roasted AR. Also AR and EAR increased a inhibitory activity of FXa compared with RAR. The blood coagulation time of administration groups were significantly increased compare with control group. The TXB2 was significantly decreased in AR and EAR.Conclusions : We confirmed that whether AR and EAR administration has anti-oxidant and anti-thrombotic effect or not. As the results, AR and EAR were improved anti-oxidant effects and blood biochemistry compare with control group. This study provides scientific evidence that AR and EAR are have an anti-oxidant effect and anti-thrombotic effect, it expected that there is no difference between the two.

• 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.

• 동의생리병리학회지
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• 제18권2호
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• pp.534-537
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• 2004

We produced twelve monoclonal antibodies(mAbs) against thyroglobulin and characterized the bindig profiles. Among them, three mAbs(TN-1, TN-2 and TN-3) were further characterized their binding specificities. TN-2 had a potent lupus anticoagulant activity and potentiated the anticoagulant effect of venom phospholipase A₂. he anticoagulant mechanism of TN-2 was elongation of the partial thromboplastin time and binding to phosphatidylserine which may have a pivot role in blood coagulation. And TN-2 was cross-reacted with ss-DNA and ds-DNA and had a characteristic of autoantibody. These results suggest that TN-2 may provide a useful tool for studying the correlation between autoimmune thyroiditis and its therapeutic effect.

• 대한한방부인과학회지
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• 제19권1호
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• pp.139-154
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• 2006

Objective : This experimental study was carried out to investigate anti-coagulation effects and mechanism of Hongdeung-tang on the dissentimenated intravascular coagulation Methods : Each 10 rats were classified as normal gorup, control group and treated group. The control group was given a 0.5mg/ml endotoxin intra-vein injection and was occurred Disseminated Intravascular Coagulation(DIC). The treated group were orally administrated 1ml Hongdeung-tang concentration once a day for 6 days and then it was treated the same as the control group. We took the blood from heart and were investigated number of Platelet and white blood cell(WBC), fibrinogen concentration, prothrombin time(PT), activated partial thromboplastin time(APTT), interleukin-6(IL-6), Tumor Necrosis $Factor-{\alpha}(TNF-{\alpha})$, Prostaglandin $E2(PGE_2)$ from them. Results : There were a statistically significant increase of platelet and fibrinogen concentration in the treated group compared to the treated group. The PT was a significantly reduced in treated group compared to the control group. There was no significant change in numbers of WBC and APTT between control and treated group. On the contrary, the number of PT, IL-6, $TNF-{\alpha}$, $PGE_2$ were significantly decreased in treated group compared to the control group. Conclusion : DIC which was occurred by endotoxin intravenous injection seems to related to the increase of IL-6, $TNF-{\alpha}$, $PGE_2$ and Hongdeung-tang has an effect that supress those factors. we can assume Hongdeung-tang has an anti-coagulation effect by those supressing effect.

• Food Science and Biotechnology
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• 제18권6호
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• pp.1423-1429
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• 2009

Rhizopus oryzae KSD-815 was isolated from nuruk that has been used to make Korean traditional wines. This study was performed to investigate the effect of cultures of R. oryzae KSD-815 on cardiovascular disorders and cancer metastasis. Firstly, these cultures were sequentially fractionationed with n-hexane (TAHe), ethylacetate (TAE), n-butanol (TAB), and $H_2O$ (TAW). The TAE inhibited the activity of angiotensin-converting enzyme (ACE) and TAB suppressed platelet aggregation in vitro. TAE and TAB inhibited cell motility of human breast cancer cells. Furthermore, TAW interrupted the formation of neovasculature and tube-like structure, and down-regulated the expression of angiogenic factors, basic fibroblast growth factor (bFGF), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in breast cancer cells. These results indicated that cultures of R. oryzae KSD-815 display the inhibitory activities on hypertension, platelet aggregation, and metastasis, and suggest that these cultures might be further probed for the purposes as therapeutic agents or dietary supplements.

• 대한수의학회지
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• 제55권4호
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• pp.233-240
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• 2015

Although the effects of the rice bran have recently been investigated, there is no information regarding platelet physiology available. However, it is well known that fermented natural plants have a beneficial effect on cardiovascular diseases. Therefore, this study was conducted to investigate whether fermented rice bran extract (FRBE) with several plants (Artemisia princeps, Angelica Gigantis Radix, Cnidium officinale, and Camellia sinensis) affected agonist-induced platelet aggregation, and if so, what the underlying mechanism of its activity was. We performed several experiments, including in vitro platelet aggregation, intracellular calcium concentration and adenosine triphosphate release. In addition, the activation of integrin ${\alpha}_{II}b{\beta}3$ was determined using fibrinogen binding. Thrombus formation was also evaluated in vivo using an arterio-venous shunt model. The FRBE inhibited collagen-induced platelet aggregation in a concentration-dependent manner. FRBE significantly and dose dependently attenuated thrombus formation using rat arterio-venous shunt. FRBE suppressed the intracellular calcium mobilization in collagen-stimulated platelets. We also found that FRBE inhibited extracellular stimuli-responsive kinase 1/2, p38-mitogen-activated protein kinases and c-Jun N-terminal kinase phosphorylation. These results suggested that FRBE inhibited collagen-induced platelet aggregation, which was mediated by modulation of downstream signaling molecules. In conclusion, FRBE could be developed as a functional food against aberrant platelet activation-related cardiovascular diseases.