• YAKHAK HOEJI
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• v.46 no.6
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• pp.441-447
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• 2002

It has been well known that vanadium shows various physiological and pharmacological properties such as an insulin-mimetic effect. In view of the reported toxic effects there is the problems that the safety margin is narrow because of its strong toxicity, Vanadate was tested for its ability to cause blood aggregation. Although vanadate or $H_2O$$_2$ alone had little effect on platelet aggregation, treatment of vanadate and $H_2O$$_2$ together induced platelet aggregation indicated that it was occurred by pervandate or hydroxyl radical produced from the reaction of vanadate and $H_2O$$_2$. It was dependent on extracellular $Ca^{2+}$ion. Platelet aggregation caused by vanadate and $H_2O$$_2$ was inhibited by ascorbic acid, tocopherol, catalase, mannitol, and Tiron. In contrast to vanadate, vanadium yeast prepared by uptaking vanadate in yeast cells did not induce platelet aggregation in the presence of $H_2O$$_2$.>.

• Biomedical Science Letters
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• v.25 no.4
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• pp.302-312
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• 2019

The aim of this work was to investigate the effect of black tea extract (BTE) on collagen -induced platelet aggregation. In this study, BTE (10~500 ㎍/mL) was shown to inhibit platelet aggregation via thromboxane A₂ (TXA₂) down-regulation by blocking cyclooxygenase-1 (COX-1) activity. Also, BTE decreased intracellular Ca²⁺ mobilization ([Ca²⁺]_i). Additionally, BTE enhanced the levels of both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are aggregation-inhibiting molecules. BTE inhibited the phosphorylation of phospholipase C (PLC) γ2 and syk activated by collagen. BTE regulated platelet aggregation via cAMP-dependent phosphorylation of vasodilator-stimulated phosphoprotein (VASP) Ser¹⁵⁷. The anti-platelet effects of BTE in high fat diet (HFD)-induced obese rats were evaluated. After eight weeks of BTE treatment (300 and 600 mg/kg), the platelet aggregation rate in the treated groups was significantly less than that in the HFD-fed control group. Also, BTE exhibited a hepatoprotective effect and did not exert hepatotoxicity. Therefore, these data suggest that BTE has anti-platelet effects on collagen-stimulated platelet aggregation and may have therapeutic potential for the prevention of platelet-mediated thrombotic diseases.

• Biomedical Science Letters
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• v.25 no.2
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• pp.123-130
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• 2019

Platelet aggregation is essential for hemostatic process in case of blood vessels damages. However, excessive platelet aggregation can cause cardiovascular disorders including atherosclerosis, thrombosis and myocardial infarction. Scopoletin is usually found in the roots of genus Scopolia or Artemisia, and is known to have anticoagulant and anti-malarial effects. This study investigated the effect of scopoletin on human platelet aggregation induced by U46619, an analogue of thromboxane $A_2(TXA_2)$. Scopoletin had anti-platelet effects by down-regulating $TXA_2$ and intracellular $Ca^{2+}$ mobilization ($[Ca^{2+}]_i$), the aggregation-inducing molecules generated in activated platelets. On the other hand, scopoletin increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are known to be intracellular $Ca^{2+}$ antagonists. This resulted in inhibition of fibrinogen binding to ${\alpha}IIb/{\beta}_3$ in U46619-induced human platelet aggregation. In addition, scopoletin inhibited the release of adenosine trisphosphate (ATP) in dose-dependent manner. This result means that the aggregation amplification activity through the granule secretion in platelets was suppressed by scopoletin. Therefore, we demonstrated that scopoletin has a potent antiplatelet effect and is highly likely to prevent platelet-derived vascular disease.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.122-126
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• 1996

In vitro inhibitory effect of aspalatone ((3-(2-methyl-4-pyronyl)]-2-acetyloxybenzoate) on collagen-, ADP-, and epinephrine-induced platelet aggregation in human platelet rich plasma (PRP) was compared with the effects of reference drugs (acetylsalicylic acid, cilostazol and ticlopidine). Aspalatone inhibited time and dose dependently human platelet aggregation induced by collagen; relative potency was in the order of cilostazol>acetylsalicylic acid>aspalatone>ticlopidine. Aspalatone, like acetylsalicylic acid, potently inhibited only the secondary phase of ADP-and epinephrine-induced aggregation. Thromboxane $B^2$ production evoked by collagen in human PRP was inhibited significantly and concentration-dependently by aspalatone and acetylsalicylic acid. These results were in agreement with the earlier studies in which the antiplatelet action of aspalatone was indicated to be due to the inhibition of platelet cyclooxygenase activity (Han et al., Arzneim. Forsch./Drug Res. 44(II), 1122, 1994; Suh and Han, Yakhak Hoeji 39, 565, 1995). In addition, the inhibitory activity of aspalatone on the platelet aggregation appears to be inversely related to the rate of nonspecific deacetylation of the drug in plasma.

• Journal of Applied Biological Chemistry
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• v.63 no.2
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• pp.131-136
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• 2020

When blood vessels are damaged, a fast hemostatic response should occur to minimize blood loss and maintain normal circulation. Platelet activation and aggregation are essential in this process. However, excessive platelet aggregation or abnormal platelet aggregation may be the cause of cardiovascular diseases such as thrombosis, stroke, and atherosclerosis. Therefore, finding a substance capable of regulating platelet activation and suppressing agglutination reaction is important for the prevention and treatment of cardiovascular diseases. 6,7-Dimethoxy-2H-chromen-2-one (Scoparone), found primarily in the roots of Artemisia or Scopolia plants, has been reported to have a pharmacological effect on immunosuppression and vasodilation, but studies of platelet aggregation and its mechanisms are still insufficient. This study confirmed the effect of scoparone on collagen-induced human platelet aggregation, TXA₂ production, and major regulation of intracellular granule secretion (ATP and serotonin release). In addition, the effect of scoparone on the phosphorylation of the phosphoproteins PI3K/Akt and mitogen-activated protein kinases (MAPK) involved in signal transduction in platelet aggregation was studied. As a result, scoparone significantly inhibited the phosphorylation of PI3K/Akt and MAPK, which significantly inhibited platelet aggregation through TXA₂ production and intracellular granule secretion (ATP and serotonin release). Therefore, we suggest that scoparone is an antiplatelet substance that regulates the phosphorylation of phosphoproteins such as PI3K/Akt and MAPK and is of value as a preventive and therapeutic agent for platelet-derived cardiovascular disease.

• Biomedical Science Letters
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• v.29 no.3
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• pp.184-189
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• 2023

Normal activation of platelets and their aggregation are crucial during hemostasis process. It appears excessive or abnormal aggregation of platelets may bring about cardiovascular diseases like stroke, atherosclerosis, and thrombosis. For this reason, finding a substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. This study examined the effect of artemisinin on regulation of U46619-induced platelet aggregation, granule secretion. In addition, the effects of artemisinin on phosphorylation of PI3K/Akt and MAPK pathway involved in platelet aggregation was studied. As a result, artemisinin significantly downregulated of PI3K/Akt and MAPK pathway. In addition, artemisinin significantly reduced granule secretion, and platelet aggregation was inhibited by artemisinin. Therefore, we suggest that artemisinin is an anti-platelet substance that regulates PI3K/Akt and MAPK pathway and is valuable as a therapeutic and preventive agent for platelet-derived cardiovascular disease.

• Toxicological Research
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• v.14 no.3
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• pp.333-339
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• 1998

Sambutoxin, a newly purified mycotoxin in Koea, caused hemorrhage in the stomach and intestine of rats. To elucidate the mechanism of hemorrhage, effects of sambutoxin on rabbit platelet aggregation were investigated. First of all, the effects of sambutoxin on the platelet aggregation response and ATP release from platelet by various appregating factors were investigated. And then the role of $Ca^{2+}$ on the platelet aggregation was investigated by flow cytometer. Finally, morphological effect of sambutoxin on platelet ultrastructure was examined by transmission electron microscope. Sambutoxin inhibited aggregation induced by ADP, collagen, thrombin, and arachidonic acid and decreased platelet activating factor-induced disaggregation time in a dose dependent manner. Sambutoxin also decreased thrombin and arachidonic acid-induced ATP release, but increased all factors induced $Ca^{2+}$ release. Sambutoxin showed severe ultrastructural changes of platelet such as appearance of disorganization debri of cellular organelle in intercellular space. Our results indicate that sambutoxin inhibitis rabbit platelet aggregation, and it may be party due to the decrease of ATP release. However, it is not clear whether the antiaggregating effect of sambutoxin is related to $Ca^{2+}$ increase.

• Biomedical Science Letters
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• v.27 no.3
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• pp.170-176
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• 2021

Thapsigargin (TG), a sarco/endoplasmic reticulum (ER) Ca²⁺-ATPase (SERCA) inhibitor, has been widely used as an agonist for platelet aggregation for decades. In this study, we investigated the effect of TG on the release of lactate dehydrogenase (LDH) for platelets and elucidated its mechanism. Platelet LDH release and platelet aggregation were increased by TG treatment; 1,000 nM of TG induced the complete lysis of platelets. Other agonists such as collagen (2.5 ㎍/mL), thrombin (0.1 U/mL), and ADP (10 mM) did not induce significant platelet LDH release despite platelet aggregation. Finally, we investigated the effects of pharmacological inhibitors on TG-induced platelet aggregation and LDH release. SP600125, a JNK inhibitor, and LY294002, a PI-3K inhibitor, inhibited TG-induced platelet LDH release but not platelet aggregation. Forskolin, an adenylyl cyclase activator, also inhibited LDH release without affecting platelet aggregation by TG. These results suggest that the TG-induced platelet aggregation was accompanied by LDH release but regulated by a different signaling pathway.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.337-345
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• 1995

The effects of ginkgolides(natural mixture of ginkgolides, ginkgolide B, ginkgolide C) and flavonoids(quercetin, kaempferol, myricetin), extracted from Ginkgo biloba, on ADP and PAF-induced platelet aggregation in vitro and ex vivo were investigated. In these experiments, both of ginkgolides and ginkgoflavonoids did not affect the ADP(5 $\mu{M}$) induced platelet aggregation in vitro. The IC$_{50}$ value on PAF (0.3 $\mu{M}$) induced platelet aggregation were 2.52 $\mu{M}$ (ginkgolide B) and 6.35 $\mu{M}$ (natural mixture of ginkgolides) and 2.80 $\mu{M}$ (mixture of ginkgolide B and quercetin). Oral administration of ginkgolide B (1 and 3 mg/kg) and quercetin (3 and 9 mg/kg) to rabbits inhibited ex vivo PAF induced platelet aggregation in a dose-dependent manner. Ginkomin-F tablets administered to the diabetic patients showed inhibitory activities on the ADP and PAF induced platelet aggregation in a dose and time dependent manner.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.239-245
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• 2013

In in vitro study, the anti-platelet aggregation effect of Shiitake mushroom extract was examined by measuring the collagen induced platelet aggregation and the DPPH radical scavenging. In in vitro study, anti-thrombotic effect of Shiitake mushroom extract was examined using the carotid artery thrombosis rat model. Carotid artery thrombosis rat model was made by 35% $FeCl_3$ treatment. After that, we investigate thrombus weight and blood flow. In platelet aggregation test, the extract significantly inhibited platelet aggregation in a concentration dependent manner(p<.001). Also, extract increased DPPH radical scavenging activity in a concentration dependent manner. Extract significantly inhibited thrombus weight to compare with control group. And blood passage time were shorter in the Shiitake mushroom extract supplemented groups than in control group. These results provide experimental evidence that Shiitake mushroom can be used to prevent platelet aggregation and thrombosis, then could apply the clinical diseases such as cardiovascular disease, and so on.