• Toxicological Research
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• 제14권3호
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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.

• 대한의생명과학회지
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• 제25권4호
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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.

• 약학회지
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• 제55권5호
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• pp.374-378
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• 2011

This study was performed to evaluate enhanced effect of fermented Galgeun tang (GGT) and Ssanghwa tang (SHT) on the anti-platelet aggregation. Platelet aggregation assay was performed In vitro using human platelet rich plasma(PRP) and In vivo using SD-rat plasma by platelet aggregometer. Pharmacodynamic parameters, $E_{max}$ and $EC_{50}$, were calculated using Winnolin. SD-rats administered 1 g/kg of oriental medicine every 12 hr for 8 days. Platelet aggregation was measured by optical method with collagen inducer (4 ${\mu}g$/ml). In In vitro anti-platelet study, $EC_{50}$ of GGT-A was lower than that of GGT-con about 79.13 ${\mu}g$/ml. And $EC_{50}$ of SHT-A and SHT-B was lower than that of SHT-con about 122.73 and 110.15 ${\mu}g$/ml, respectively. It is assumed that fermented GGT and SHT were more effective than original medicine. In multiple administration study, anti-platelet effect was significantly increased both GGT and SHT. Fermented GGT and SHT were more effective than original herbal medicine on anti-platelet aggregation.

• Biomolecules & Therapeutics
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• 제4권2호
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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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• 제63권4호
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• pp.339-345
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• 2020

Euchrestaflavanone A (EFA) is a flavonoid found in the root bark of Cudrania tricuspidata. C. tricuspidata extract, widely used throughout Asia in traditional medicine, has been investigated phytochemically and biologically and is known to have anti-obesity, anti-inflammatory, and anti-tumor effects. It has been reported that C. tricuspidata extract also possesses anti-platelet effects; however, the mechanism of its anti-platelet and anti-thrombotic activities is yet to be elucidated. In this study, we investigated the effects of EFA on the modulation of platelet function using collagen-induced human platelets. Our results showed that EFA markedly inhibited platelet aggregation. Furthermore, it downregulated glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production, and clot retraction, but upregulated the cyclic adenosine monophosphate-dependent pathway. Taken together, EFA possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• 대한의생명과학회지
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• 제13권1호
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• pp.11-15
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• 2007

We examined the effects of pregnancy and pregnancy-induced hypertension (PIH) on platelet activation. Thirty-six women with PIH (blood pressure > 140/90 mm Hg after two consecutive measurements after the $24^{th}$ weeks of gestation) without proteinuria, fifty-six normotensive pregnant women, and fifty non-pregnant women were studied. WBC, RBC, platelet related variables, including mean platelet component (MPC), mean platelet volume (MPV) and platelet component distribution width (PCDW) were determined for this study. MPC levels were significantly lower in women with PIH compared with normotensive pregnant women and non-pregnant women (P<0.05). MPC levels were inversely con-elated with PIH (r=-0.49, P<0.001), systolic BP (r=-0.22, P<0.01), diastolic BP (r=-0.17, P<0.005), WBC (r=-0.30, P<0.001), MPV (r=-0.41, P<0.001), and PCDW (r=-0.68, P<0.001), and positively con-elated with RBC (r=0.32, P<0.001), platelet count (r=0.21, P<0.05), and mean platelet mass (MPM) (r=0.18, P<0.05). MPC levels were found to be an independent factor associated with PIH and PCDW (P<0.01) after adjustments were made for potential confounding factors such as gestational age, systolic blood pressure, diastolic blood pressure, WBC, RBC, Platelet count, and PCDW. In conclusion, MPC levels were significantly lower in women with PIH, and MPC levels were found to be an independent factor associated with PIH and PCDW. Therefore, platelet activation is suggested as a useful predictor for patients with PIH.

• Journal of Chest Surgery
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• 제25권3호
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• pp.240-246
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• 1992

The effects of extracorporeal circulation on plateler count were studied in 120 patients. We measured platelet count before, during, after extracorporeal circulation, and postoperative 0, 1, 3, 5, 7, 9, 11th days to evaluate the effects of total extracorporeal circulation time and types of oxygenator on changes of platelet count The patients were classified into group I [extracorporeal circulation time < 100 minutes, 45 patients], II [100 < extracorporeal circulation time < 200 minutes, 48 patients], III [extracorporeal circulation time >200 minutes, 27 patients], and also all patients were classified into group B [bubble oxygenator, 84 patients] and group M [membrane oxygenator, 36 patients]. The group I, II, III were subclassified into IB, IM, IIB, IIM, IIIB and IIIM according to the types of oxygenator. The results were as follows: 1. The platelet counts were reduced throughout extracorporeal circulation and in the early postoperative periods upto postoperative third day. 2. The platelet counts after postoperative 9th to 11th day increased significantly compared with those of preoperative levels. 3. After extracorporeal circulation, the platelet recovered gradually in all groups, especially faster in group I compared with those of group II and III. 4. The effect of the type of oxygenator on the recovery of platelet count was not significant. In conclusion, extracorporeal circulation time influenced the change of platelet count. Therefore, in order to prevent of decrease of platelet count associated with extracorporeal circulation time, the extracorporeal circulation time should be shortened.

• Biomolecules & Therapeutics
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• 제3권2호
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• pp.132-135
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• 1995

Several clofibrate congeners (bezafibrate, gemfibrozil and fenofibrate) were investigated the relationship between effects on the aggregation induced by aggregating agents (thrombin, arachidonic acid, ADP and collagen) and arachidonic acid metabolism in rabbit homogenized platelet. In platelet aggregation study, all drugs produced no significant inhibition (data not shown) in arachidonic acid and thrombin. Also platelet aggregation by ADP was not changed in bezafibrate and Inhibited dose dependently in fenofibrate and gemfibrozil. Platelet aggregation by collagen was inhibited dose dependently and significantly (from p<0.5 to p<0.001) by gemfibrozil and fenofibrate at concentrations between 20 and 400 $\mu$M. In arachidonic acid metabolism study, synthesis of thromboxane $B_2$ was not changed in rabbit platelet membranes and that of prostaglandin $E_2$ and $F_{2{\alpha}}$ was slightly increased by all drugs. It was concluded that clofibrate congeners inhibited ADP and collagen induced rabbit platelet aggregation and inhibition of collagen induced aggregation was probably mediated through some mechanism (pathway) other than arachidonic acid metabolism, judging from arachidonic acid metabolites (thromboxane $B_2$, prostaglandin $E_2$and $F_{ 2{\alpha}}$) synthesis in rabbit homogenized Platelet.

• 생약학회지
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• 제17권2호
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• pp.161-167
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• 1986

The smear method developed by Velaskar and Chitre was modified to allow the screening of plant extracts and/or fractions for platelet anti-aggregating activity. The modified smear method was also found suitable for massive screening of pure compounds. Sample fractions prepared from various plant extracts were examined for their effects against ADP, arachidonic acid (AA) or collagen induced platelet aggregations. Several solvent fractions of plant extracts including water fraction prepared from the methanol extract of Acanthopanax sp. was inhibitory against rat platelet aggregations. The activity guided treatments and fractionations of the water fraction from A. senticosus Max yielded two anti-platelet aggregatory substances, 3, 4-dihydroxybenzoic acid (I) and its artefact ethyl 3, 4-dihydroxybenzoate(II). The inhibitory activities of I and II against rat platelet aggregation were compared with that of aspirin, a known inhibitor of platelet aggregation. Discussions also included the results of the investigations on the structural activity relationships among the various dihydroxybenzoic acid derivatives against platelet aggregations induced by either one of ADP, AA or collagen.

• Journal of Applied Biological Chemistry
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• 제63권2호
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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.