• Korean Journal of Clinical Pharmacy
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• v.2 no.1
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• pp.1-9
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• 1992

Protective effect of urokinase on reperfusion were studied followed by global ischemia in the isolated perfused rat heart. Separately, anti-platelet aggregation effect of urokinase also investigated. Urokinase exhibited positive effect for the protection of rat heart function by increasing the LV dp/dt, coronary flow(CF) and the Tate pressure product(RPP), and by decreasing the LVEDP on reperfusion. Urokinase also decreased arrhythmia by $74.7\%(P<0.05) induced by global ischemia in the rat heart. In the platelet aggregation study, urokinase did not show the inhibitory effect of ADP or collagen induced platelet aggregation inviuo and exvivo.

• BMB Reports
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• v.40 no.5
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• pp.678-683
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• 2007

Extracts from the leaves of the Ginkgo biloba are becoming increasingly popular as a treatment that is claimed to reduce atherosclerosis, coronary artery disease, and thrombosis. In this study, the effect of ginkgolide B (GB) from Ginkgo biloba leaves in collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation was investigated. It has been known that human platelets release matrix metallo-proteinase-9 (MMP-9), and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GB to form an MMP-9 (86-kDa) on gelatinolytic activities. And then, activated MMP-9 by GB dose-dependently inhibited platelet aggregation, intracellular $Ca^{2+}$ mobilization, and thromboxane $A_2$ ($TXA_2$) formation in collagen-stimulated platelets. Activated MMP-9 by GB directly affects down-regulations of cyclooxygenase-1 (COX-1) or $TXA_2$ synthase in a cell free system. In addition, activated MMP-9 significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have the anti-platelet function in resting and collagen-stimulated platelets. Therefore, we suggest that activated MMP-9 by GB may increase the intracellular cAMP and cGMP production, inhibit the intracellular $Ca^{2+}$ mobilization and $TXA_2$ production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that activated MMP-9 is a potent inhibitor of collagen-stimulated platelet aggregation. It may act a crucial role as a negative regulator during platelet activation.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.380.3-380.3
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• 2002

Rhus verniciflua Stokes (RVS) is a widely used herbal plant with various biological properties. Our previous study using in vitro platelet aggregation in whole blood showed that ethyl acetate layer of RVS had strong anti-aggregatory activity. In this study. to investigate the anti-aggregatory activity and antioxidative effects of RVS ethyl acetate layer. the layer was subsequently fractionated by ODS columm chromatograph (50% MeOH). As a result. the fraction 3 was most inhibited the aggregation of platelet in rat whole blood induced by thrombin and all fraction of RVS was detected strong antioxidative effect. (omitted)

• Korean Journal of Pharmacognosy
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• v.51 no.2
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• pp.100-106
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• 2020

The extract of Cudrania tricuspidata is used in ethnomedicine throughout Eastern Asia in China, Korea and Japan. In Korean traditional medicine, Cudrania tricuspidata has been used to treat eczema, mumps, tuberculosis, contusions, insomnia and acute arthritis. In addition, it has been reported that root extract of Cudrania tricuspidata has anti-platelet effects. Therefore, we investigated which compound in Cudrania tricuspidata has inhibitory effect on platelet aggregation. In this study, we tried to explain the inhibitory mechanism of steppogenin from Cudrania tricuspidata on human platelet aggregation. Collagen-induced human platelet aggregation and [Ca²⁺]_i mobilization were dose-dependently inhibited by steppogenin and we determined the inhibition by steppogenin is due to the down regulation of extracellular-signal-regulated kinase(ERK) and inositol-1,4,5-triphosphate receptor type I(IP₃RI) phosphorylation. In addition, steppogenin inhibited collagen-induced fibronectin adhesion to αIIb/β3 and thromboxane A₂ generation. Thus, in the present study, steppogenin showed an inhibitory effect on human platelet aggregation, suggesting its potential use for preventing platelet-induced cardiovascular disease.

• YAKHAK HOEJI
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• v.58 no.5
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• pp.322-327
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• 2014

In this study, we investigated whether the mixtures of onion water extract and aloe ethanol extracts have antiplatelet activities. The mixtures inhibited collagen- and thrombin-induced rat platelet aggregation in vitro. Additionally, the oral administration of the mixtures inhibited platelet aggregation induced by collagen ex vivo but not prolonged mouse tail vein bleeding time in vivo. These results suggest that the combination of onion and aloe extracts has a potential to be a preventive agent against platelet-mediated disorders.

• Biomedical Science Letters
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• v.16 no.4
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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.

• Microbiology and Biotechnology Letters
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• v.47 no.1
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• pp.20-24
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• 2019

Moringa oleifera Lam (MOL) has been used as a traditional medicine to treat various cancers and inflammation. Whereas the bioactivities of the MOL leaf and seed are well reported, the study of the root is still rudimentary. In this study, the ethanol extract of MOL (EEMOL) and its subsequent organic solvent fractions were prepared and their anticoagulation activity in vitro and platelet aggregation inhibitory activity were evaluated. The EEMOL had negligible anticoagulation and strong platelet aggregation activities. However, the hexane and ethyl acetate fractions of EEMOL showed significant inhibition against thrombin, prothrombin, coagulation factors, and platelet aggregation, without hemolytic activity up to 1.0 mg/ml. Our results suggest that the active fractions of MOL root have potential as new anti-thrombosis agents.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.223-230
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• 2017

Platelets play an essential role in hemostasis through aggregation and adhesion to vascular injury sites but their unnecessary activation can often lead to thrombotic diseases. Upon exposure to physical or biochemical stimuli, remarkable platelet shape changes precede aggregation or adhesion. Platelets shape changes facilitate the formation and adhesion of platelet aggregates, but are readily reversible in contrast to the irrevocable characteristics of aggregation and adhesion. In this dynamic phenomenon, complex molecular signaling pathways and a host of diverse cytoskeleton proteins are involved. Platelet shape change is easily primed by diverse pro-thrombotic xenobiotics and stimuli, and its inhibition can modulate thrombosis, which can ultimately contribute to the development or prevention of thrombotic diseases. In this review, we discussed the current knowledge on the mechanisms of platelet shape change and also pathological implications and therapeutic opportunities for regulating the related cytoskeleton dynamics.

• Journal of Life Science
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• v.28 no.9
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• pp.1068-1075
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• 2018

Kaempferia parviflora, an herbaceous plant in the family Zingiberaceae, is popular in many tropical regions. It is called as black ginger or krachaidum in Thailand and Laos, and its raw or dried root have been used as spices and teas. The rhizomes also have been traditionally used to treat gastrointestinal disorders, ulcers, gout, dysentery, allergies and to improve physical work capacity. Recently, its anti-obesity, anti-oxidant, anti-inflammatory and blood clot-lysis activities were reported. In this study, the anti-thrombosis activity of black ginger was investigated, since improvement in blood fluidity leads to the prevention of various lifestyle-related diseases. The hot water and ethanol extract and their subsequent solvent fractions (hexane, ethylacetate, butanol fractions and water residue) were prepared, and their anti-coagulation and platelet aggregation inhibitory activities were determined, respectively. Among the black ginger extracts and their fractions, the ethylacetate fraction (EAF) of ethanol extract only showed significant extensions of blood coagulation time determined by thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (aPTT). At 5 mg/ml concentration, TT, PT and aPTT were extended to 1.22, 1.49 and >15-folds compared to non-treatment. The EAFs of ethanol and hot water extract showed strong inhibitions against collagen-induced platelet aggregations, which are comparable to inhibitions of aspirin. Also the EAFs from black ginger did not show any hemolysis activity against human RBC up to 0.5 mg/ml. Our results suggest that the EAF of black ginger has a potential as novel anti-coagulation and ant-platelet aggregation agent. This report provides the first evidence of anti-coagulation activity of black ginger.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.12
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• pp.298-305
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• 2019

Cudrania tricuspidata has been reported to have many biological activities, including anti-inflammatory, anti-cancer, and antioxidant properties. However, the effects of C. tricuspidata root extract (CTE) on human platelet aggregation induced by collagen as well as the signaling pathways involved remain unknown. In the present study, we investigated the effect of CTE on human platelets. CTE inhibited platelet aggregation via down-regulation of thromboxane A₂ (TXA₂) by blocking cyclooxygenase-1 (COX-1) activity and intracellular Ca²⁺ mobilization in collagen-induced platelets. CTE also reduced the phosphorylation of phospholipase C (PLC) γ2 and syk. CTE regulated platelet aggregation via cyclic guanosine monophosphate (cGMP)-dependent phosphorylation of vasodilator-stimulated phosphoprotein (VASP) Ser²³⁹. In addition, administration of CTE (50 and 100 mg/kg) significantly reduced hyper-aggregated platelet aggregation by collagen (5 ㎍/mL) without hepatotoxicity in HFD (high fat diet)-fed rats. Taken together, these results suggest that CTE has anti-platelet effects both in vitro and in vivo. Therefore, CTE may be an effective therapeutic and preventive agent for cardiovascular disease, and is a safe and natural product.