• 약학회지
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• 제38권1호
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• pp.97-101
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• 1994

Platelets play a very important role in nomal hemostasis and their functions are more enhanced in various pathogenic states than in normal state. Especially it has been postulated that abnormal platelet and endothelium function might be major factors of microcirculatory disturbance in diabetes mellitus. Hydroxybrazilin, a phenolic constituent of Hematoxylon campechianum has been examined for its inhibitory effect on platelet aggregation. Its antiaggregatory effect might be mediated through the decrease of ATP release from dense granule and those of thromboxane $A_2$ production in normal and streptozotocin induced diabetic rats. The present study was undertaken to gain insight into the mechanism that hydroxybrazilin inhibited thromboxane $A_2$ production in platelets. Thus we measured the effect of hydroxybrazilin on phospholipase $A_2$, a rate limiting step of thromboxane $A_2$ production, in normal and streptozotocin induced diabetic rats. Hydroxybrazilin significantly inhibited the platelet phospholipase $A_2$ activity in normal and streptozotocin induced diabetic rats.

• 대한의생명과학회지
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• 제23권4호
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• pp.310-320
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• 2017

Ginseng has been widely used for traditional medicine in eastern Asia and is known to have inhibitory effects on cardiovascular disease (CVD) such as thrombosis, atherosclerosis, and myocardial infarction. Because, platelet is a crucial mediator of CVD, many studies are focusing on inhibitory mechanism of platelet functions. Among platelet activating molecules, thromboxane $A_2$ ($TXA_2$) and P-selectin play a central role in CVD. $TXA_2$ leads to intracellular signaling cascades and P-selectin plays an important role in platelet-neutrophil and platelet-monocyte interactions leading to the inflammatory response. In this study, we investigated the inhibitory mechanisms of total saponin fraction from Korean red ginseng (KRG-TS) on $TXA_2$ production and P-selectin expression. Thrombin-elevated $TXA_2$ production and arachidonic acid release were decreased by KRG-TS dose (25 to $150{\mu}g/mL$)-dependently via down regulation of microsomal cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS) activity and dephosphorylation of cytosolic phospholipase $A_2$ ($cPLA_2$). In addition, KRG-TS suppressed thrombin-activated P-selectin expression, an indicator of granule release via dephosphorylation of mitogen-activated protein kinases (MAPK). Taken together, we revealed that KRG-TS is a beneficial novel compound inhibiting $TXA_2$ production and P-selectin expression, which may prevent platelet aggregation-mediated thrombotic disease.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.879-884
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• 2002

Previous study showed that an amidrazonophenylalanine derivative, LB30057, which has high water solubility, inhibited the catalytic activity of thrombin potently by interaction with the active site of thrombin. In the current investigation, we examined whether LB30057 inhibited platelet aggregation and vascular relaxation induced by thrombin. Treatment with LB30057 to plateletrich plasma (PRP) isolated from human blood resulted in a concentration-dependent inhibition of thrombin-induced aggregation. Values for $IC_{50}$ and $IC_{100}$ were $54{\pm}4$ nM and $96{\pm}3$ nM, respectively. This inhibition was agonist (thrombin) specific, since $IC_{50}$ values for collagen and ADP were \much greater than those for thrombin. In addition, concentration-dependent inhibitory effects were observed on the serotonin secretion induced by thrombin in PRP. Consistent with these findings, thrombin-induced increase in cytosolic calcium levels was inhibited in a concentration-dependent manner. When LB30057 was treated with aortic rings isolated from rats, LB30057 resulted in a concentration-dependent inhibition of thrombin-induced vascular relaxation. All these results suggest that LB30057 is a potent inhibitor of platelet aggregation and blood vessel relaxation induced by thrombin.

• 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.

• 한국한의학연구원논문집
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• 제13권2호통권20호
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• pp.143-148
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• 2007

The present study examined inhibitory effects of 20 efficient experience prescriptions on platelet aggregation induced by collagen in human whole blood using the impedance method of aggregometry. Among them, a hot water extract of KIOM 2003-080 was selected to be the most effective candidate. In an in vivo study using a mouse acute thrombosis model, the anti-thrombotic effects of the KIOM2003-080 crude extract were also observed. In addition, we accessed bio-marker of platelet activation using thromboxane B2 by ELISA assay. A significantly decrease in thromboxane B2 production was seen in the presence of KIOM2003-080. Consequently, the results from this experiment provide pharmacological evidence for the traditional use of KIOM2003-080 prescription, suggesting that its hot water extracts could be used to prevent platelet aggregation and thrombosis disease.

• Food Science and Biotechnology
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• 제14권5호
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• pp.685-688
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• 2005

Antibacterial and antiplatelet activities of Acorus gramineus rhizome-derived asaronaldehyde and asaron were analyzed using platelet aggregometer and six human intestinal bacteria. Active constituent of A. gramineus rhizome was isolated and characterized as asaronaldehyde by spectral analyses. At 2 and 1 mg/disk, asaronaldehyde exhibited strong inhibition of Clostridium perfringens and C. difficile without adverse effects on growth of beneficial bacteria such as Bifidobacterium bifidum, Lactobacillus acidophilus, and L. casei. Asaron also revealed moderate growth inhibition against C. perfringens and C. difficile at 2 mg/disk, no growth-inhibiting activity was observed on B. bifidum, L. acidophilus, L. casei, and E. coli. At 50% inhibitory concentration ($IC_{50}$) value, asaronaldehyde was effective in inhibiting platelet aggregation induced by collagen ($IC_{50}$, $27.6\;{\mu}M$) and arachidonic acid ($IC_{50}$, $53.7\;{\mu}M$). These results suggest asaronaldehyde may be useful as lead compound for inhibiting platelet aggregation induced by collagen and arachidonic acid.

• 생명과학회지
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• 제28권9호
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• pp.1068-1075
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• 2018

흑생강은 생강과 초본과 뿌리식물로 태국 및 라오스에서는 크라차이담으로 불리며, 뿌리는 향신료와 차로 이용되어 왔다. 말린 뿌리는 위장장애, 통풍, 이질, 알러지 치료 및 강장용으로 전통적으로 이용되어 왔으며, 최근에는 항비만, 항산화, 항염증, 혈전 용해 활성 등의 다양한 유용 생리활성이 보고되어 있다. 본 연구에서는 흑생강의 혈액순환 개선 활성을 확인하기 위해, 흑생강 지하부의 ethanol 추출물 및 열수 추출물을 조제하고 각각 이의 순차적 유기용매 분획물인 hexane 분획물, ethylacetate (EA) 분획물, butanol 분획물 및 물 잔류물을 조제하여 각각의 성분을 분석하였고, 혈전 생성과 관련된 항응고 활성, 혈소판 응집저해 활성 및 적혈구 용혈활성을 평가하였다. 그 결과, ethanol 추출물의 EA 분획물 5 mg/ml 농도에서 TT, PT, aPTT를 각각 1.22, 1.49 및 15배 이상 연장시켜 강력한 항응고 활성을 나타냄을 확인하였으며, ethanol 및 열수 추출물의 EA 분획물 모두에서 동량의 아스피린보다 강력한 혈소판 응집저해 활성을 확인하였다. 또한 상기 EA 분획물들은 0.5 mg/ml 농도까지 인간 적혈구에 대한 용혈활성을 나타내지 않았다. 본 연구 결과는 흑생강의 혈전 생성 억제 활성에 대한 최초의 보고이며, 흑생강의 EA 분획물이 인간 적혈구 용혈활성 없이 강력한 항응고 및 혈소판 응집저해 활성을 나타내어 신규의 항혈전제로 이용 가능함을 제시하고 있다.

• Toxicological Research
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• 제20권2호
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• pp.137-142
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• 2004

We investigated the effects of plant vinegar on platelets and blood coagulation system. Plant vinegar inhibited in vitro platelet aggregation in a concentration dependent manner, when platelets were activated by thrombin and collagen. In addition, plant vinegar showed inhibitory effects on the serotonin secretion induced by thrombin in a concentration dependent manner. However, treatment with plant vinegar to platelets did not induce any cytotoxicity, as determined by the release of lactate dehydrogenase. Plant vinegar did not change the coagulation parameters such as activated partial thromboplastin time (aPTT) and prothrombin time (PT) using rat citrated plasma. In vivo study revealed that, treatment with plant vinegar prolonged the bleeding time from mouse tail. All these results suggest that plant vinegar might improve blood hemostasis mediated via anti platelet activities.

• Journal of Ginseng Research
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• 제21권2호
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• pp.132-140
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• 1997

The effects of ginsenosides purified from red ginseng on platelet aggregation were investigated. Preincubation of washed platelets from rats with either ginsenoside Rg3, ginsenosides non-polar fraction (G-NPF), ginsenoside Rg1(Rg1) or ginsenosides polar fraction(G-PF) reduced the plytelet aggrelation induced by collagen in a dose-dependent manner, whereas ginsenoside Rg2 failed to inhibit the aggregation. Their IC50 values of Rg3, G-NPF, Rgl, and G-PF were 8.7$\pm$1.0, 150.3$\pm$0.1, 369.9$\pm$ 1.0, 606.211.3 $\mu\textrm{g}$/ml, respectively. Aggrelation induced by thrombin was also inhibited by Rg3 and G-NPF with IC50 being 5.2$\pm$ 1.1 and 66.5$\pm$0.8 $\mu\textrm{g}$/ml, respectively. The alterations of Intracellular Ca2+ concentration in platelets were monitored using fura-2 as a fluorescent Ca2+ indicator. Both Ca2+ release from internal stores and Ca2+ influx into cytosol were suppressed by Rg3. Rg3 also inhibited granular release of ATP and TXA2 formation induced by thrombin in a dose-dependent manner in the washed platelets. Rg3 also inhibited Aggregation and ATP release from human platelets induced by collagen to a similar extent as were observed in rat platelets. In conclusion, Rg3 is a Potent anti-aggregating component in ginsenosides and may exert its anti-aggrega1ing activity by decreasing TXAa formation and granular secretion in platelets, most likely by inhibiting Ca2+ influx and Ca2+ mobilization from intracellular stores. Thus ginseng may contribute to the prevention and treatment of thrombosis.

• 한국미생물·생명공학회지
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• 제42권3호
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• pp.302-306
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• 2014

이화누룩은 증자하지 않은 쌀을 물에 불린 후 분쇄하고, 이를 솔잎으로 띄워 발효시킨 한국 전통누룩이다. 이화누룩의 기능성을 평가하기 위해 이화누룩의 에탄올 추출물과 이의 순차적 유기용매 분획물을 조제하고 항혈전 활성을 평가하였다. 그 결과, ethylacetate 분획물은 강력한 thrombin time, prothrombin time, aPTT 연장효과를 나타내었으며, 유기용매 분획후의 물 잔류물에서는 강력한 혈소판 응집저해능이 확인되었다. 본 연구결과는 이화누룩의 ethylacetate 분획이 신규의 항혈전제로 사용 가능함을 나타내며, 이는 이화누룩의 항혈전 활성에 대한 최초의 보고이다.