• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.201-205
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• 2011

Although various biological activities of resveratrol have been extensively studied, most reports have focused on trans-resveratrol and little attention has been paid to the cis-isomer. In this study, the effect of cis-resveratrol on platelet activity was examined and compared with that of the trans-isomer. Treatment with cis-resveratrol resulted in inhibition of platelet aggregation induced by thrombin, collagen or ADP, which are representative aggregation-inducing agents, and the trans-isomer elicited the same effects. These effects were concentration-dependent in the range of 1-100 ${\mu}M$. However, the potency of the cis-isomer was much lower than that of the trans-isomer; the $IC_{50}$ values for the cis-isomer versus the trans-isomer were $31{\pm}12$ vs $151{\pm}3$, $161{\pm}3$ vs $91{\pm}4$, and $601{\pm}15$ vs $251{\pm}6\;{\mu}M$ for thrombin-, collagen- and ADP-induced aggregation, respectively. These results indicate that cis-resveratrol has a less potent anti-platelet activity, compared with the trans-isomer, and raise the possibility that the biological activities of the cis-isomer may be different from those of the trans-isomer. It will be necessary to evaluate the activity of cis-resveratrol independently of the trans-isomer.

• Journal of Applied Biological Chemistry
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• v.65 no.1
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• pp.57-62
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• 2022

Excessive activation and aggregation of platelets is a major cause of cardiovascular disease. Therefore, inhibition of platelet activation and aggregation is considered an attractive therapeutic target in preventing and treating cardiovascular diseases. In particular, strong platelet activation and aggregation by collagen secreted from the vascular endothelium are characteristic of vascular diseases. Artesunate is a compound extracted from the plant roots of Artemisia or Scopolia species, and has been reported to be effective in anticancer and Alzheimer's disease fields. However, the effect and mechanism of artesunate on collagen-induced platelet activation and aggregation have not been elucidated. In this study, the effect of artesunate on collagen-induced human platelet aggregation was confirmed and the mechanism of action of artesunate was clarified. Artesunate inhibited the phosphorylation of PI3K/Akt and Mitogen-activated protein kinases, which are phosphoproteins that are known to act in the signal transduction process when platelets are activated. In addition, artesunate decreased TXA₂ production and decreased granule secretion in platelets such as ATP and serotonin release. As a result, artesunate strongly inhibited platelet aggregation induced by collagen, a strong aggregation inducer secreted from vascular endothelial cells, with an IC₅₀ of 106.41 µM. These results suggest that artesunate has value as an effective antithrombotic agent for inhibiting the activation and aggregation of human platelets through vascular injury.

• Journal of Nutrition and Health
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• v.30 no.2
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• pp.132-138
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• 1997

This study was conducted to investigate hypocholesteroloemic effect of garlic and onion in rats fed basal diet or cholesterol supplemented diets. Thirty Sprague Dawley rats were fed basal diet and 30 rats were fed basal diet plus 0.5% cholesterol, both containing none(control), 3% garlic or 3% onion for 4 weeks. Supplementation of 0.5% cholesterol significantly increased plasma and liver cholesterols(p<0.01) and liver triglyceride(TG) and plasma glucose(p<0.05). Plasma total cholesterol was significantly decreased in both garlic and onion groups compared to control when they were fed cholesterol supplemented diet(p<0.05). Plasm TG wa significantly decreased in onion groups regardless cholesterol supplementation (p<0.05). There were no differences in plasma glucose and HDL-cholesterol and liver total cholesterol and TG among groups in both basal and choleserol supplemented diets. Platelet aggregation was rather increased in onion group but not singnificantly different.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.823-829
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• 2002

The thrombosis importantly came to the front as the risk factor of these circulation system's disease. SilsoSanGami(SSG) was used for investigating the inhibitory effect on platelet-activating factor-induced platelet aggregation about drugs that used to improvement various symptoms created by the thrombosis in oriental medicine. In this study, the water-extracted SSG was investigated for its possible antithrombotic action on platelets. The antithrombotic activity of water-extracted SSG was deduced from its ability to suppress platelet aggregation, ATP-exocytosis, and the generation of prostaglandin E₂ and thromboxane A₂ by human platelets, stimulated with arachidonic acid. Water-extracted SSG dose-dependently suppressed the aggregation of human platelets, the release of endogenous ATP, and the formation of PGE₂ and TXB₂, both the latter usually detected to estimate the activity of COX and TXS, respectively. Since the IC/sub 50/ values necessary to inhibit COX (115 ㎍/㎖ SSG) and TXS(74 ㎍/㎖ SSG) were in the same range, inhibition of COX is suggested to be the primary target of water-extracted SSG, thus suppressing the formation of PGE₂ which is metabolized by TXS to TXA₂. We considerated that SSG has practical applicational value of clinical trial in the thrombosis caused by platelet aggregation.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.206.1-206.1
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• 2003

From methanol extract of Acanthopnanax senticosus, six platelet anti-aggregating compounds, chiisanogenin (1), chiisanoside (2), ursolic acid (3), oleanolic acid (4), b-sitosterol (5) and daucosterol (6) were isolated. All of the isolated compounds showed dose-dependent inhibitory activities to rat platelet aggregation induced by all the agonist employed. Compound 1 showed about 50 folds higher potency than acetylsalicylic acid (ASA) on U46619 induced platelet aggregation (IC$\sub$50/ : 6.21 ${\mu}$M) and 10 ∼ 20 folds higher effect than ASA on epinephrine and arachidonic acid (AA) induced aggregation (IC$\sub$50/ ; 2.50 and 4.81 ${\mu}$M, respectively). (omitted)

• Journal of Oriental Neuropsychiatry
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• v.23 no.1
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• pp.115-128
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• 2012

Objectives : To evaluate the in vitro scavenging activity, inhibitory effect of LDL oxidation of pro-oxidant reactive species, anti-platelet aggregative effects and anti-thrombosis effects in response to treatment with SA using various screening methods including biological and non-biological oxidants. Methods : The antioxidant activity concerning extract from SA was studied with in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$-induced human LDL oxidation and the inhibitory effect on thrombin-induced platelet aggregation and thrombosis. Results : SA extracts were found to have a potent scavenging activity regarding oxidative stress as well as an inhibitory effect towards LDL oxidation, platelet aggregation, and thrombosis. Conclusions : The SA extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drugs against oxidative stress and atherosclerosis.

• Journal of Food Hygiene and Safety
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• v.19 no.3
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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.

• Korean Journal of Veterinary Research
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• v.55 no.4
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• pp.233-240
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• 2015

Although the effects of the rice bran have recently been investigated, there is no information regarding platelet physiology available. However, it is well known that fermented natural plants have a beneficial effect on cardiovascular diseases. Therefore, this study was conducted to investigate whether fermented rice bran extract (FRBE) with several plants (Artemisia princeps, Angelica Gigantis Radix, Cnidium officinale, and Camellia sinensis) affected agonist-induced platelet aggregation, and if so, what the underlying mechanism of its activity was. We performed several experiments, including in vitro platelet aggregation, intracellular calcium concentration and adenosine triphosphate release. In addition, the activation of integrin ${\alpha}_{II}b{\beta}3$ was determined using fibrinogen binding. Thrombus formation was also evaluated in vivo using an arterio-venous shunt model. The FRBE inhibited collagen-induced platelet aggregation in a concentration-dependent manner. FRBE significantly and dose dependently attenuated thrombus formation using rat arterio-venous shunt. FRBE suppressed the intracellular calcium mobilization in collagen-stimulated platelets. We also found that FRBE inhibited extracellular stimuli-responsive kinase 1/2, p38-mitogen-activated protein kinases and c-Jun N-terminal kinase phosphorylation. These results suggested that FRBE inhibited collagen-induced platelet aggregation, which was mediated by modulation of downstream signaling molecules. In conclusion, FRBE could be developed as a functional food against aberrant platelet activation-related cardiovascular diseases.

• Journal of Nutrition and Health
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• v.32 no.4
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• pp.384-393
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• 1999

The degree of platelet aggregation, thromboxane B2(TXB2)formation and fatty acid composition of platelet phospholipids(PL) were investigated in 24 healthy male subjects who for five weeks consumed either corn oil(CO) rich in linoleic acid(LA), perilla oil (PO) rich in $\alpha$-linoleic acid($\alpha$-LAN), or canola oil(CNO) rich in oleic acid(OA) as a major fat source. Total fat intake was 30% of total calories and prescribed oil intake of each dietary group was 50% of the total fat intake. In the CO group, significantly decreased contents of polyunsaturated fatty acids(PUFA), n-6 PUFA, n-3 PUFA and eicosapentanoic acid(EPA) were observed, and significantly increased contents of OA and saturated fatty acids(SFA) were observed in platelet PL after 3 weeks and 5 weeks of dietary treatment. In the PO group, contents of OA and docosahexanoic acid(DHA) were increased, and the ratio of n-6/n-3 was decreased significantly in platelet PL after dietary treatment. The CNO group showed significatnlty decreased contents of PUFA, P/S ratio, n-6 PUFA, LA,(EPA+DHA)/arachidonic acid(AA), and significantly increased SFA contents after 3 weeks of the oil-based diet. The dietary-induced effects on fatty acid composition of platelet PL were observed mostly after 3 weeks of the oil-based diet. The dietary-induced effects on fatty acid composition of platelet PL were observed mostly after 3 weeks. Plasma TXB2 levels were increased after 3 and 5 weeks of dietary treatment. However, only the CO and CNO groups showed significantly increased plasma TXB2 levles after 3 and 5 weeks of dietary treatment. However, only the CO and CNO groups showed significantly increased plasma TXB2 levels after 5 weeks of experimental diets, when compared with initial values. Degree of platelet aggregation increased only in the CO group after dietary treatment. As a result, at week 5 the degree of platelet aggregation of the CO group was significantly higher than those of the PO and CNO groups. Among the three oil-based diets, the PO-based diet seems to have beneficial effects on atherosclerosis by influencing plasma TXB2 levels and the degree of platelet aggregation, while the CO-based diet showed the most adverse effects. Our results imply that plasma TXB2 levels might be affected by dietary fatty acid composition.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.60-70
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• 2015

In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP ($Ser^{157}$) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP ($Ser^{157}$) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to ${\alpha}IIb/{\beta}3$. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to ${\alpha}IIb/{\beta}3$are due to stimulation of cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.