• Archives of Pharmacal Research
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• 제29권11호
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• pp.952-956
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• 2006

A phytochemical investigation of stems from Salvadora persica resulted in the first isolation of four benzylamides from a natural source. The isolated compounds were identified as butanediamide, $N^{1},\;N^{4}$-bis(phenylmethyl)-2(S)-hydroxy-butanediamide (1), N-benzyl-2-phenylacetamide (2), N-benzylbenzamide (3) and benzylurea (4). The structure elucidation was accomplished using spectroscopic methods, especially 2D NMR and HREIMS. Compound 2 revealed a significant inhibitory effect on human collagen-induced platelet aggregation, and a moderate antibacterial activity against Escherichia coli.

• Biomolecules & Therapeutics
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• 제8권3호
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• pp.223-227
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• 2000

Propolis, a natural resinous compound collected from honey bees, contains many biochemical constituents and has been used for traditional medicines as early as 300 B .C. Recently, it has been reported to possess many biological activities such as antibacterial, antiviral, fungicidal, local anaesthetic, immunostimulating, antiinflammatory and free radical scavenging properties. To investigate activities of chrysin, one of propolis effective compounds for blood coagulation system was injected endotoxin (4000 EU/kg, i.v.) in rats at 1 hr after administered chrysin (20 mg/kg, p.o.). This study was resulted that chrysin has antiplatelet aggregation activity in vitro, delay of blood clotting time and prothrombin time, and reduction of fibrinogen and FDP in vivo. Chrysin has increased SOD activity, GSH content and GST activity, and decreased MDA content in liver. The result suggests that the antithrombosis effect of chrysin is suppressive activity for a blood coagulation system and antioxidative activity.

• Biomolecules & Therapeutics
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• 제9권4호
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• pp.258-262
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• 2001

In the advanced age, cardiovascular disease is more serious than any other disease. Especially, the thrombus causes the serious disease like apoplexia, carebri and myocardial infarction. Thrombosis is caused by the injury of endothelium and the alterations in normal blood flow. To investigate activities of Carthamus tinctorius L. Semen butanol fraction for blood coagulation system, endotoxin (4000EU/kg) was injected (i..v) to rats at 1hr after administration of Carthamus tinctorius L. Semen butanole fraction (500 mg/kg, p.o.). Carthamus tinctorius L. Semen butanol fraction was found to have antiplatelet activity in vitro. In vivo it showed a delay of blood clotting time, and prothrombin time, and reduction of fibrinogen and FDP It also increased SOD activity, and decreased MDA content. These results suggest that the antithrombosis effect of Carthamus tinctorius L. Semen butanol frac tion results from suppressive activity for a blood coagulation system and antioxidative activity.

• 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.

• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2004년도 춘계학술대회
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• pp.253-257
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• 2004

Platelet aggregation is a complex phenomenon that probably involves several intracellular biochemical pathways. When activated, platelets change shape, aggregate and release the contents of their intracellular granules. The interactions between platelets and blood vessel walls are important in the development of thrombosis and cardiovascular diseases. When blood vessels are damaged, platelet aggregation occurs rapidly to form haemostatic Plugs or arterial thrombi at the sites of vessel injury or in regions where blood flow is disturbed. These thrombi are the source of thromboembolic complications of atherosclerosis, heart attacks, stroke, and peripheral vascular disease. Therefore, the inhibition of platelet function represents a promising approach for the prevention of thrombosis. Plants constitute a rich source of bioactive chemicals such as phenolics, terpenoids and alkaloids. Plant extracts may be an alternative to currently used medicinal source because they constitute a rich source of bioactive chemicals. This study was performed to investigate the antiplatelet activity of extract of Tabebuia impetiginosa Martius ex DC (Taheebo) and find out which fractions to this activity in rabbit platelet. Taheebo was methanol extracted and solvent fractionated in to five fractions (hexane, chloroform, ethylacetate, butanol and water). And each fractions were investigated inhibitory effects on platelet aggregation induced by various agonists using washed rabbit platelets in vitro.

• 한국식품위생안전성학회지
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• 제19권3호
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• pp.161-166
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• 2004

We investigated the antiplatelet effect of a newly synthesized guanidine derivative KR-32558, a sodium-hydrogen exchanger-1 (NHE-1) inhibitor, together with the elucidation of the possible mechanisms of action. KR-32558 concentration -dependently inhibited the aggregation of washed rabbit platelets induced by collagen (10 ${\mu}g/ml$) with an $IC_{50}$ value of 85.9 ${\mu}M$, but with much weaker potency against aggregation induced by thapsigargin (0.5 ${\mu}M$) or A23187 (5 ${\mu}M$). And had no effect on platelet aggregation induced by arachidonic acid (100 ${\mu}M$), thrombin (0.05 U/ml) and U46619 (1 ${\mu}M$) up to 100 ${\mu}M$. KR-32558 completely inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at concentration of 100${\mu}iM$. Taken together, these observation suggest that KR-32558 selectively inhibited collagen-mediated platelet aggregation by blocking the cytoplasmic calcium mobilization in addition to NHE-1 inhibition.

• Journal of Ginseng Research
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• 제39권3호
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• pp.279-285
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• 2015

Background: Korean Red Ginseng has been used as a traditional oriental medicine to treat illness and to promote health for several thousand years in Eastern Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major active ingredients responsible for Korean Red Ginseng's therapeutic activity against many kinds of illness. Although the crude saponin fraction (CSF) displayed antiplatelet activity, the molecular mechanism of its action remains to be elucidated. Methods: The platelet aggregation was induced by collagen, the ligand of integrin ${\alpha}_{II}{\beta}_I$ and glycoprotein VI. The crude saponin's effects on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate (ATP) release] were determined. The activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3-kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of integrin ${\alpha}_{II}b{\beta}_{III}$ was examined by fluorocytometry. Results: CSF strongly inhibited collagen-induced platelet aggregation and ATP release in a concentration-dependent manner. It also markedly suppressed $[Ca^{2+}]_i$ mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly inhibited the fibrinogen binding to integrin ${\alpha}_{IIb}{\beta}_3$. Conclusion: Our present data suggest that CSF may have a strong antiplatelet property and it can be considered as a candidate with therapeutic potential for the treatment of cardiovascular disorders involving abnormal platelet function.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.69-69
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• 1997

In the screening of tropical medicinal plants using PAE receptor binding assay, the ether extract of Ardisia crispa showed the potent antagonistic activity. Ardisia crispa have been used to heal the scurf, earache, orchitis, fever and diarrhoea, cough and given to the mother after childbirth to ‘wash out dirty blood’ in Malaysia. By means of activity guided isolation, compound AC7-1 was isolated as the potent PAF antagonist. In this study, antiplatelet effects of compound AC7-1 were examined in vitro platelet aggregation assay using the chronolog aggregometer. Compound AC7-1 inhibited PAF-, collagen-, ADP-, thrombin-induced platelet aggregation in human, rabbit and rat platelet rich plasma. In vitro rabbit platelet aggregation, the IC$\_$50/ value of compound AC7-1 was 5 ${\times}$ 10$\^$-6/ M against PAF(5 ${\times}$ 10$\^$-7/M)-induced aggregation. The IC$\_$50/ values of AC7-1 on PAF-induced platelet aggregation increased with increase of the concentration of PAF used. This result suggested the competitive nature of the AC7-1 antagonism. In vitro rat platelet aggregation, the IC$\_$50/ values of AC7-1 on collagen-, ADP-induced platelet aggregation were 4 ${\times}$ 10$\^$-6/ M, 2 ${\times}$ 10$\^$-5/ M, respectively. Also in vitro human platelet aggregation, AC7-1 potently inhibited both the primary phase and secondary phase of thrombin-induced aggregation.

• 대한수의학회지
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• 제56권2호
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• pp.67-74
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• 2016

Tomato extract has been shown to exert antiplatelet activity in vitro and to change platelet function ex vivo, but with limitations. In this study, antiplatelet activity of water soluble tomato concentrate (Fruitflow I) and dry water soluble tomato concentrate (Fruitflow II) was investigated using rat platelets. Aggregation was induced by collagen and adenosine diphosphate and granule-secretion, $[Ca^{2+}]_i$, thromboxane B2, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were examined. The activation of integrin ${\alpha}_{IIb}{\beta}_3$ and phosphorylation of signaling molecules, including mitogen-activated protein kinase (MAPK) and PI3K/Akt, were investigated by flow cytometry and immunoblotting, respectively. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were examined. Moreover, in vivo thrombus weight was tested by an arteriovenous shunt model. Fruitflow I and Fruitflow II significantly inhibited agonist induced platelet aggregation, adenosine triphosphate and serotonin release, $[Ca^{2+}]_i$, and thromboxane B2 concentration, while having no effect on cAMP and cGMP levels. Integrin ${\alpha}_{IIb}{\beta}_3$ activation was also significantly decreased. Moreover, both concentrates reduced phosphorylation of MAPK pathway factors such as ERK, JNK, P38, and PI3K/Akt. In vivo thrombus formation was also inhibited. Taken together, these concentrates have the potential for ethnomedicinal applications to prevent cardiovascular ailments and can be used as functional foods.

• Journal of Ginseng Research
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• 제41권1호
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• pp.96-102
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• 2017

Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.