• Preventive Nutrition and Food Science
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• v.18 no.3
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• pp.181-187
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• 2013

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 ($TXA_2$) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and $TXA_2$, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation.

• Preventive Nutrition and Food Science
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• v.12 no.3
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• pp.141-147
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• 2007

Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is used in the treatment of various diseases such as cancer and chronic inflammation. We recently reported that cordycepin has a novel antiplatelet effect through the down regulation of $[Ca^{2+}]_{i}$ and the elevation of cGMP/cAMP production. In this study, we further investigated the effect of cordycepin on collagen-induced platelet aggregation in the presence of cGMP-dependent protein kinase (PKG)- or cAMP-dependent protein kinase (PKA)-inhibitor. PKG inhibitor Rp-8-pCPT-cGMPS potentiated the collagen-induced platelet aggregation, but PKA inhibitor Rp-8-Br-cAMPS did not. However, both Rp-8-pCPT-cGMPS and Rp-8-Br-cAMPS reduced inhibition by cordycepin of collagen-induced platelet aggregation. Moreover, cordycepin inhibited $Ca^{2+}-dependent$ phosphorylation of both 47 kDa- and 20 kDa-protein in the presence of both PKG inhibitor and PKA inhibitor. Taken altogether, these results suggest that the inhibitory effect of cordycepin on collagen-induced platelet aggregation is associated with cGMP/PKG- and cAMP/PKA-pathways, and thus cordycepin may be an efficacious intervention against platelet aggregation-mediated thrombotic disease.

• 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 Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.460-466
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• 2006

We wondered whether the mechanisms of antiplatelet aggregation of DJS-WE were through multiple pathways. Danggijakyak-san(DJS) consisting of 6 herbes of Paeoniae Radix, Poria Cocos, Angelicae Sinensis Radix, Cnidii Rhizoma, Atractylodis Macrocephalae Rhizoma and Alismatis Rhizoma, is a crude mixture of a commonly used Korean herbal medicine. The water extract (DJS-WE) of DJS has been known to have an anti-platelet aggregation activity. We have reported that DJS-WE inhibited ADP-induced aggregation as well as arachidonic acid-induced aggregation of human platelet. Clinical studies on the cardiovascular effects of DJS-WE have been done in Korea. The DJS has been used as a remedy for gastrointestinal disorders (abdominal pain, dysentery), headache, amenorrhea, and postpartum hemorrhage. It has also been claimed to have a remarkable central stimulant effect, a transient hypertensive effect, and positive inotropic and chronotropic effects. In this paper, we evaluated the possible mechanisms of the antiplatelet activity of DJS-WE using human platelets. On the other hand, the role of DJS-ethanol extract on the inhibition of platelet aggregation and hemolytic effect have not yet been investigated in detail. We also used the method of activated partial thromboplastin times (APTT) for the first time to study the inhibition on platelet aggregation activity of DJS-ethanol extract. The effect of DJS-WE on hemolysis was also investigated. DJS-WE showed a high hemolysis ability on human blood.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.193.3-194
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• 2003

Platelets play critical roles in both hemostasis and thrombosis. It was reported that platelet aggregation is associated with an increase in superoxide production and can be inhibited by hydroxyl radical scavengers. In the course of our search for the anti-platelet, anti-coagulant and/or anti-oxidative components from plants, the MeOH extract of Crassula cv. "Himaturi" (Crassulaceae) was observed to have both anti-aggregatory and anti-coagulant effects. A novel compound, 12-O-(4'-O-methyl-galloyl)-bergenin (1), was isolated as an active component from the EtOAC soluble fraction. (omitted)

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.160-165
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• 2018

Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

• Biomedical Science Letters
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• v.24 no.3
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• pp.280-284
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• 2018

The incidence of cardiovascular diseases (CVDs) is increasing rapidly in developed countries, with CVDs now representing the leading cause of morbidity and mortality. Natural products and ethnomedicines have been shown to reduce the risk of CVDs. Garlic is a medicinal plant used throughout the world for its anti-inflammatory, antioxidant, and antiplatelet activities. Chitosan is a natural polysaccharide obtained from chitin, and derivatives of chitosan have been shown to inhibit platelet aggregation and adhesion. We hypothesized that fermented preparations of these products may possess stronger antiplatelet effects than the non-fermented forms owing to the increased bioavailability of the bioactive compounds produced during fermentation. Therefore, we compared these compounds via in vitro and ex vivo platelet aggregation assays by using standard light transmission aggregometry and ex vivo granule secretions from rat platelets. We found that fermented preparations exerted more potent and significant inhibition of platelet aggregation both in vitro and ex vivo. Likewise, ATP release from dense granules of platelets was also significantly inhibited in fermented preparation-treated rat platelets compared to that in non-fermented preparation-treated ones. We concluded that fermented preparations exerted more potent effects on platelet function both in vitro and ex vivo, possibly as a result of the increased bioavailability of active compounds produced during fermentation. We therefore suggest that fermented products may be potent therapeutics against platelet-related CVDs and can be used as antiplatelet and antithrombotic agents.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.73-78
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• 2008

Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C.A. Meyer), has been shown to have a variety of biological functions such as immunostimulating and anti-tumor activities. In the present study, we investigated whether RGAP inhibited ligand-induced platelet aggregation. The washed platelet-rich plasma was prepared from male SD rats with successive centrifugation. The platelets $(10^8/ml)$ were preincubated with 1 mM of $CaCl_2$ for 2 min either in the presence or in the absence of RGAP $(10{\sim}50\;{\mu}g/ml)$ and were stimulated with collagen (2.5 ${\mu}g/ml$) and thrombin (0.1 U/ml). RGAP dose-dependently inhibited thrombin-induced platelet aggregation with $IC_{50}$ value of $26.2{\pm}2.0$ ${\mu}g/ml$. In collagen-induced platelet aggregation, RGAP inhibited the reaction with an $IC_{50}$ value of $31.5{\pm}3.0\;{\mu}g/ml$. RGAP potently suppressed the intracellular calcium ion, which was stimulated by thrombin (0.1 U/ ml). Among mitogen-activated protein kinase (MAPK) subtypes, the extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK were analyzed in the present study. RGAP inhibited the phosphorylation of ERK2 and p38 MAPK, which was activated by collagen (2.5 ${\mu}g/ml$). Finally, these results suggested that besides saponin fraction, RGAP take an important role in the preventive effect of Korean red ginseng against cardiovascular disease such as thrombosis and atherosclerosis.

• Biomedical Science Letters
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• v.29 no.1
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• pp.41-47
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• 2023

Discovery of new substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artesunate is a compound from plant roots of Artemisia or Scopolia, and its effects have shown to be promising in areas of anticancer and Alzheimer's disease. However, the role and mechanisms by which artesunate affects the aggregation of platelets, and the formation of a thrombus are currently not understood. This study examined the ways artesunate affects platelets activation and thrombus formation induced by collagen. As a result, cAMP and cGMP production were increased significantly by artesunate relative to the doses, as well as phosphorylated VASP and IP₃R, substrates to cAMP-dependent kinase and cGMP-dependent kinase, in a significant manner. The Ca²⁺ normally mobilized from the dense tubular system was inhibited due to IP₃R, phosphorylation from artesunate, and phosphorylated VASP aided in inhibiting platelet activity via αIIb/β₃ platelet membrane inactivation and inhibiting fibrinogen binding. Finally, artesunate inhibited thrombin-induced thrombus formation. Therefore, we suggest that artesunate has importance with cardiovascular diseases stemming from the abnormal platelets activation and thrombus formation by acting as an effective prophylactic and therapeutic agent.

• Journal of Life Science
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• v.18 no.3
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• pp.357-362
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• 2008

The dried roots of Aralia continentalis Kitagawa is known to have the potential for anti-inflammation and anti-rheumatic, but their effects on thrombosis are not clear. In this study, we evaluated the anti-platelet and antioxidative activities of A. continentalis Kitagawa. Methanol extract and its various fractions of A. continentalis Kitagawa inhibited ADP-induced platelet aggregation, and EtOAc fraction showed strongest inhibition in a concentration-dependent manner with a $IC_{50}$ value of 217.7 ${\mu}g/ml$. Moreover, the EtOAc fraction contained 77.7% of 1,1-diphenyl-2-picrylhydrazyl(DPPH) and 43.1% of 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging activity at 0.1 mg/ml. In addition, the methanol and EtOAc fraction dose-dependently inhibited thrombin-stimulated platelet adhesion to collagen or fibrinogen. Collectively, these results suggest that the polyphenol-rich EtOAc fraction from A. continentalis Kitagawa can reduce platelet hyperactivation by scavenging free radicals. Thus, the EtOAc fraction of A. continentalis Kitagawa is a potential source for inhibition of platelet-dependent thrombosis.