• Microbiology and Biotechnology Letters
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• v.43 no.4
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• pp.373-377
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• 2015

The mature fruit of Sorbus commixta is known as magaja in Korea and is consumed in the form of tea and wine. In addition, it has been used to treat hypertension and articular neuralgia in folk medicine. In this study, the ethanol extract of magaja and its subsequent organic solvent fractions were prepared, and their in vitro anti-coagulation, and platelet aggregation inhibitory activities were evaluated. Among the fractions, the ethylacetate fraction demonstrated significant inhibition against thrombin, prothrombin, blood coagulation factors and platelet aggregation, without hemolysis activity up to 0.5 mg/ml. Our results suggest that the ethylacetate fraction of magaja has the potential to be used as a new anti-coagulation agent.

• Biomedical Science Letters
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• v.22 no.4
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.3
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• pp.511-515
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• 2002

Paeoniae radix has been considered as one of the most important crude drugs used in traditional oriental medicine and has been employed as a circulatory tonic in care of weakness, night sweats, and lumbar pain, etc. Platelet activation plays an important role in thrombosis and haemostasis. Active compounds for the inhibition of platelet activation from Paeoniae radix were extracted and fractionated into five fractions. Its fraction two and three of ethyl acetate extract inhibited the aggregation of washed rabbit platelets induced by collagen. Two active compounds, bezoyloxypaeoniflorin and paeoniflorin, were isolated from fraction two and three by silica gel column and high performance liquid chromatography. The chemical structures were determined by comparison of their proton and carbon nuclear magnetic resonance spectra. Benzoyloxypaeoniflorin showed strong inhibition at the concentration of 100 ug/mL against collagen-induced washed rabbit platelets aggregation. It is suggested that Paeoniae radix has become food material to prevent a cardiovascular disease.

• Journal of Applied Biological Chemistry
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• v.63 no.3
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• pp.235-241
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• 2020

An essential component of the hemostatic process during vascular damage is platelet activation. However, many cardiovascular diseases, such as atherosclerosis, thrombosis, and myocardial infarction, can develop due to excessive platelet activation. Isoscopoletin, found primarily in plant roots of the genus Artemisia or Scopolia, has been studied to demonstrate potential pharmacological effects on Alzheimer's disease and anticancer, but its mechanisms and role in relation to thrombus formation and platelet aggregation have not yet been discovered. This research investigated the effect of isoscopoletin on collagen-induced human platelet activation. As a result, isoscopoletin strongly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in a concentration-dependent manner. In addition, isoscopoletin greatly phosphorylated inositol 1,4,5-triphosphate receptor (IP₃R) and vasodilator-stimulated phosphoprotein (VASP), known substrates of cAMP-dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by isoscopoletin induced Ca²⁺ inhibition from the dense tubular system Ca²⁺ channels, and VASP phosphorylation was involved in fibrinogen binding inhibition by inactivating αIIb/β₃ in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clot production and finally reduced thrombus formation. Therefore, this research suggests that isoscopoletin has strong antiplatelet effects and is likely to be helpful for thrombotic diseases involving platelets by acting as a prophylactic and therapeutic agent.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.354-364
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• 2015

Background: Intracellular $Ca^{2+}$($[Ca^{2+}]_i$) is a platelet aggregation-inducing molecule. Therefore, understanding the inhibitory mechanism of $[Ca^{2+}]_i$mobilization is very important to evaluate the antiplatelet effect of a substance. This study was carried out to understand the $Ca^{2+}$-antagonistic effect of total saponin from Korean Red Ginseng (KRG-TS). Methods: We investigated the $Ca^{2+}$-antagonistic effect of KRG-TS on cyclic nucleotides-associated phosphorylation of inositol 1,4,5-trisphosphate receptor type I ($IP_3RI$) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in thrombin (0.05 U/mL)-stimulated human platelet aggregation. Results: The inhibition of $[Ca^{2+}]_i$ mobilization by KRG-TS was increased by a PKA inhibitor (Rp-8-BrcAMPS), which was more stronger than the inhibition by a cyclic guanosine monophosphate (cGMP)- dependent protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). In addition, Rp-8-Br-cAMPS inhibited phosphorylation of PKA catalytic subunit (PKAc) ($Thr^{197}$) by KRG-TS. The phosphorylation of $IP_3RI$ ($Ser^{1756}$) by KRG-TS was very strongly inhibited by Rp-8-Br-cAMPS compared with that by Rp-8-BrcGMPS. These results suggest that the inhibitory effect of $[Ca^{2+}]_i$ mobilization by KRG-TS is more strongly dependent on a cAMP/PKA pathway than a cGMP/PKG pathway. KRG-TS also inhibited the release of adenosine triphosphate and serotonin. In addition, only G-Rg3 of protopanaxadiol in KRG-TS inhibited thrombin-induced platelet aggregation. Conclusion: These results strongly indicate that KRG-TS is a potent beneficial compound that inhibits $[Ca^{2+}]_i$ mobilization in thrombin-platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic disease.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.227-233
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• 1999

The effects of 2-bromo-3-(3,5-tert-butyl-4-hydroxylphenyl)-1,4-naphthalenedione(TPN2), a synthetic vitamin K derivative, on platelet aggregation and its action mechanisms were investigated in rat platelet. TPN2 inhibited the platelet aggregation induced by collagen($10\mu\textrm{g}$/ml), thrombin(0.1 U/ml), A23187($10\mu\textrm{M}$) and arachidonic acid($100\mu\textrm{M}$) in concentration-dependent manner with $IC_{50}$ values of 6.5$\pm$1.3, 59.3$\pm$4.5, 13.0$\pm$2.37 and 2.9$\pm$$1.0\mu\textrm{M}$, respectively. Collagen-induced serotonin release was significantly reduced by TPN2. The elevation of intracellular free $Ca^{2+}$ concentration ([$Ca^{2+}$]i) by collagen stimulation was greatly decreased by the pretreatment of TPN2, which was due to the inhibition of calcium release from intracellular store and influx from outside of the cell. TPN2 also significantly reduced the thromboxane $A_2$($TXA_2$) formation in a concentration-dependent manner. The collagen-induced arachidonic acid (AA) release in [$^3H$]-AA incorporated platelet, an indicative of the phospholipase $A_2$ activity, was decreased by TPN2 pretreatment. TPN2 significantly inhibited the activity of thromboxane synthase, but did not affect the cyclooxygenase activity. From these results. it is suggested that TPN2 exert its antiplatelet activity through the inhibition of the intra-cellular $Ca^{2+}$ mobilization and the decrease of the $TXA_2$ synthesis.

• Biomedical Science Letters
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• v.24 no.3
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• pp.253-262
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• 2018

Platelets are activated at sites of vascular injury via several molecules, such as adenosine diphosphate, collagen and thrombin. Full platelet aggregation is absolutely essential for normal hemostasis. Moreover, this physiological event can trigger circulatory disorders, such as thrombosis, atherosclerosis, and cardiovascular disease. Therefore, platelet function inhibition is a promising approach in preventing platelet-mediated circulatory disease. Many studies reported the involvement of mitogen-activated protein kinases (MAPKs) signaling pathways in platelet functions. However, these studies were limited. Thus, we examined MAPK signaling pathways in human platelets using specific MAPK inhibitors, such as PD98059, SB203580, and SP600125. We observed that these inhibitors were involved in calcium mobilization and influx in human platelets. They also suppressed thrombin-induced ${\alpha}$- and ${\delta}$-granule release. These results suggest that PD98059, SB203580, and SP600125 exhibit $Ca^{2+}$ antagonistic effects.

• The Journal of Dong Guk Oriental Medicine
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• v.8 no.1
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• pp.171-190
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• 1999

This following is effect of Buthus martensi Karsch(BMK) extract on dextran-thrombus model, KCN-induced coma, cytotoxicity of brain etc. BMK extract significantly increased number of platelet and fibrogen and significantly shortened the prothrombin time as compared with control group treated with dextran. BMK extract didn't affect the changes of hematocrit as compared with control group treated with dextran. BMK extract induced a significant inhibition of human platelet aggregation induced by thrombin and ADP but did not affect human platelet aggregation induced by collagen. BMK extract showed a protective effect on pulmonary thrombosis induced by collagen and epinephrine. BMK extract prolonged the duration of KCN-induced coma and showed a protective effect on cytotoxicity of PC12 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner. These results suggested that BMK extract might be usefully applied for prevention and treatment of thrombosis and brain damage.

• Archives of Pharmacal Research
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• v.20 no.6
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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.

• Korean Journal of Pharmacognosy
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• v.52 no.1
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• pp.26-33
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• 2021

During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.