• The Journal of Korean Medicine
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• 제30권6호
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• pp.1-8
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• 2009

Objectives: Formulas for treatment of yin or yang deficiency conditions have been commonly used in traditional Korean medicine. The aim of this study is to examine the possible inhibitory effects of yin- or yang-tonifying formulas on in vivo anti-platelet activity and in vivo anti-thrombotic activity. Methods: We tested the effects of 26 types of yin- or yang-tonifying formulas on platelet aggregation induced by collagen in human whole blood using the impedance method of aggregometry and accessed a biomarker of platelet activation using thromboxane $B_2$ immunoassay. We also tested the anti-thrombotic effects of effective candidates on experimental models of thrombosis in mice. Results: 3 types of yin-tonifying formulas and 3 types of yin-yang-tonifying formulas were selected to be the most effective candidates (p<0.01). Also, through in vivo study, the antithrombotic activities of Igyeong-tang, Gamisipjeondaebo-tang, and Gamisoyo-san-treated groups, with recovery rate of 60, 50, and 45.45%, respectively, were observed to be higher than those of the control group (saline, 36.8%) in mouse acute thrombosis. Conclusion: These results show that yin-tonifying formulas are more effective in anti-platelet and anti-thrombotic activity than yang-tonifying formulas.

• 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.

• Journal of Applied Biological Chemistry
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• 제65권4호
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• pp.463-469
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• 2022

Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A₂ generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca²⁺ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser¹⁷⁵⁶), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A₂ generation and associated signaling molecules, including cytosolic phospholipase A₂ and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β₃) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Journal of Physiology & Pathology in Korean Medicine
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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 Life Science
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• 제24권5호
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• pp.515-521
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• 2014

The oriental traditional medicine, Aruncus dioicus var kamtschaticus (ADK) is used for hemostasis (blood stopping) and the promotion of blood circulation. Recently, the demands of the aerial part of ADK as edible mountain herbs are rapidly increased due to its unique fragrance and bioactivity. In this study, to evaluate the anti-thrombosis activity of ADK, ethanol extract and organic solvent fractions were prepared from aerial parts of ADK, and their anticoagulation and anti-platelet aggregation activities were determined. In an anticoagulation activity assay, the ethanol extract of ADK increased the thrombin time, prothrombin time, and activated partial thromboplastin time (aPTT) 1.4-2.3 times at a concentration of 5 mg/ml. Among the fractions, the ethylacetate fraction showed strong inhibitory effects against blood clotting factors, as shown in an extension of the aPTT. In contrast, the butanol fraction strongly promoted blood clotting. In an anti-platelet aggregation assay, the activity of the ethanol extract was comparable to that of aspirin, a commercial anti-platelet aggregation agent, and the butanol fraction showed 2-fold higher aggregation inhibitory activity than aspirin. The aforementioned ethanol extract and active fractions have ignorable hemolytic activity against human red blood cells up to a concentration of 0.5 mg/ml. Considering the high content of total polyphenol, total flavonoid, and total sugar of the ethylacetate and butanol fractions, the purified active substances have potential as safe and novel anti-thrombosis agents. This report provides the first evidence of anti-thrombosis activity of ADK.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.122-127
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• 2023

Cardiovascular disease (CVD) is increasingly increasing as the main cause of death worldwide, and activation of platelet in vascular damage is one of the important causes of CVD. In recent, there is a growing interest in anti-thrombotic materials through platelet suppression, and efforts are being made to reduce side effects by using natural bioactive compounds. Known as one of the Flavonoids, hydroxygenkwanin (HGK) is a purified substance in Daphne Genkwa, which is known to have antibacterial, anti-inflammatory and anti-cancer effects, and has been reported to serve as an inhibitor of tissue factor that prevents thrombosis, but its anti-platelet effects and the action mechanisms is not known. In this study, we confirmed that the effects of HGK on the collagen-induced human platelets activation. HGK suppressed phosphorylation of PI3K/AKT and mitogen-activated protein kinases during platelet signaling, and reduced granule secretion in platelets such as ATP and serotonin. In addition, HGK inhibited the phosphorylation of cPLA₂ and strongly undermined the production of TXA₂, which is a powerful aggregation amplifier. As a result, the platelet aggregation derived by Collagen, a cohesive induced substance, was strongly suppressed by HGK to an IC₅₀ of 86.36 µM. Therefore, HGK might be worth the antithrombotic substance that inhibits the activation and aggregation of human platelets that occur through blood vessel damage.

• Korean Journal of Pharmacognosy
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• 제19권2호
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• pp.99-101
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• 1988

3, 4-Dihydroxybenzoic acid and it's artefact ethyl ester obtained from Acanthopanax senticosus Max. were tested ex vivo and found to show mild inhibitory activities against rat platelet aggregation.

• Natural Product Sciences
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• 제9권4호
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• pp.270-272
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• 2003

The methanol extract of Euphorbia milii exhibited strong inhibitory effect on platelet aggregation in the cource of our search for anti-platelet component from succulent plants. Two components, components 1 and 2 were isolated from this plant. 1 was the mixture of 72% of 1-octacosanol (1a) and 28% of 1-triacontanol (1b), and 2 was identified as ${\beta}-sitosterol$. 2 ($IC_{50}$: $195\;{\mu}M$, and $170\;{\mu}M$ respectively) was about two fold stronger than ASA ($IC_{50}$: $420\;{\mu}M$ and $340\;{\mu}M$ respectively) on both collagen and U46619 induced aggregation, while the effect of 1 to platelets was negligible.

• Korean Journal of Pharmacognosy
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• 제26권1호
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• pp.74-77
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• 1995

Several coumarins isolated from Angelica sp. were described to show inhibitory effects against human platelet aggregation. The anti-thrombotic and anti-platelet potential was evaluated, in this paper, with the BuOH soluble fraction of Angelica dahurica root. The BuOH fraction was divided into five subfractions fr. A - E and tested in the mouse model of thrombosis. Survival was enhanced to 35% with fr. A or fr. E treated (500 mg/Kg, p.o.) group of mice compared with 5% survival of the control group. However, none of the 8 coumarin glycosides obtained from fr. A, at the conc. of 0.5 mg/ml, showed inhibitory effects against rat platelet aggregation induced by ADP or collagen.

• Korean Journal of Pharmacognosy
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• 제26권4호
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• pp.385-389
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• 1995

MeOH extract of Gastrodia elata was fractionated to five solvent fractions, hexane fr (fr I), 90% MeOH fr (fr II), EtOAc fr (fr III), BuOH fr (fr IV) and $H_2O$ fr (fr V). Among the five fractions, fr II, III and IV showed platelet anti-aggregating effects against ADP or collagen induced rat platelet aggregation in vitro. Fr II , III and IV were also tested in vivo, in the mouse and rat models of thrombosis. Oral administration of fr II, III or IV enhanced the recovery from the thrombotic shock in the mouse model of thrombosis to 32-40% from 17% of recovery with the control group of mice. Treatment with fr II, III or IV also attenuated the sudden reduction in the blood platelet count following intravenous collagen injection to rat. The above results were indicative of the presence of anti-platelet and anti-thrombotic components in this plant.