• The Journal of Korean Obstetrics and Gynecology
• /
• v.27 no.1
• /
• pp.152-166
• /
• 2014

Purpose: The purpose of this study is to compare with the result of experimental study about antithrombotic effect by reviewing recent oriental medicine journals that have been published since 2001' in Korea. Methods: Articles on antithrombotic effect that have been published from 2001' to 2013' in oriental medicine journals registered National Research Foundation of Korea were searched. After that, 12 articles using same 'thrombosis condition model' were selected and reviewed. Results: The results were as follows. 1. If there is no limit drug concentrations, platelet aggregation induced by adenosine diphosphate (ADP) in hyulbuchukeo-tanggamibang (HBCT) was the largest aggregation inhibitory effect and platelet aggregation induced by epinephrine in Saegeum-san (SGS), Jogan-tanggagambang (JGTG), hyulbuchukeo-tanggamibang (HBCT) had a large inhibitory effect on aggregation. 2. At the lowest concentration, Mokdan-san (MDS) of the inhibition of platelet aggregation induced by ADP and Hyunhosaik-san (HHS) of the inhibition of platelet aggregation induced by epinephrine were effective. 3. Pulmonary embolism induced by collagen and epinephrine in Neungasojeok-tang (NSJT) has the highest antithrombotic effect. 4. Pathological conditions of extravasated blood by dextran, Jogan-tanggagambang (JGTG) has the highest inhibitory effect on decrease in platelet numbers. Compared to the rest of the experimental drug, Saegeum-san (SGS), Heanggyonghonghwa-tang (HGTHHT), Wusl-san (WSS), Mokdan-san (MDS) showed significant inhibitory effect on the prothrombin time (PT) increases. Honghwadanggui-san (HDS), Saegeum-san (SGS) showed significant inhibitory effect on increase in activated partial thromboplastin time (APTT) and Jogan-tanggagambang (JGTG), Heanggyonghonghwa-tang (HGTHHT) showed significant inhibitory effect on decrease in fibrinogen. Conclusions: This result will provide useful information for the prescriptions of antithrombotic medicine in the field of Oriental medicine. We will have to carry out further studies that will compare each herb used in the diseases caused by extravasated blood.

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

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

• Biomolecules & Therapeutics
• /
• v.19 no.4
• /
• pp.472-476
• /
• 2011

Hypercholesterolemia indirectly increases the risk of arterial and venous thrombosis by enhancing the ability of platelets to aggregate. Yacon (Smallanthus sonchifolius) is composed of fructooligosaccharides, proteins, minerals and phenolic compounds, and has potential benefits for the management of diabetes. This study investigated whether the consumption of yacon in the diet inhibits platelet aggregation under hypercholesterolemic conditions. Male New Zealand white rabbits were fed one of five dietary interventions: a normal control diet, 0.5% cholesterol diet, 0.5% cholesterol diet+a low dose of yacon (0.5 g/kg body weight given orally each day), 0.5% cholesterol diet+a high dose of yacon (2.5 g/kg body weight given orally each day), or a 0.5% cholesterol diet+lovastatin (2 mg/kg body weight given orally each day). After 8 weeks, blood was collected to measure the amount of collagen- and thrombin-induced platelets present. Yacon inhibited the platelet aggregation induced by low doses of agonists (0.5 ${\mu}g/mL$ collagen and 0.02 units/ml thrombin) in a concentration-dependent manner. In addition, yacon concentration-dependently inhibited collagen-induced arachidonic acid liberation. Moreover, n-hexane, chloroform and ethyl acetate fractions showed a marked and selective inhibition of the platelet aggregation induced by collagen, again in a dose-dependent manner. These fractions, especially that of chloroform, significantly suppressed platelet aggregation. The results of this study demonstrate that when yacon is added to a cholesterol-enriched diet, cholesterol-induced platelet aggregation returns to control levels. This may also be beneficial in preventing atherosclerosis and reducing risk factors for coronary artery disease and stroke.

• Journal of Ginseng Research
• /
• v.46 no.1
• /
• pp.54-61
• /
• 2022

Ginseng has been widely studied due to its various therapeutic properties on various diseases such as cardiovascular disease (CVD). Cardiovascular disease has been canonically known to be caused by high levels of low-density lipoproteins (LDL) in the bloodstream, in addition to the impaired vasodilatory effects of cholesterol. However, current research on CVD has revealed a cascade of mechanisms involving a series of events that contribute to the progression of CVD. Although this has been elucidated and summarized in previous studies the detailed correlation between platelet aggregation and innate immunity that plays an important role in CVD progression has not been thoroughly summarized. Furthermore, immune cell subtypes also contribute to the progression of plaque formation in the subendothelial layer. Thrombus formation and the coagulation cascade also have a vital role in the progression of atherosclerosis. Hence, in this mini review we aim to elucidate, summarize, and propose the potent therapeutic effect of ginseng on CVD, mainly on platelet aggregation, plaque formation, and thrombus formation.

• Journal of Nutrition and Health
• /
• v.34 no.2
• /
• pp.141-149
• /
• 2001

This study done to investigate the hypocholesterolemic effect of ow dietary fiber in a high cholesterol diet in aspect of cholesterol absorption and excretion using Sprague Dawley rats. After feeding diets containing 0.5% cholesterol and 5% tangerine pulp, sea tangle or prickly pear cactus for four weeks, we measured the levels of plasma and liver cholesterol and triglyceride, fecal neutral sterols and fecal radioactivity after ingestion 14(sup)C-cholesterol. We also examined platelet aggregation and histological change in liver tissues in association of hypercholesterolemia. The liver to body weight ratio was significantly(p<0.01) lower in rats fed prickly pear cactus than in other groups. The levels of plasma total cholesterol, LDL-cholesterol and triglyceride were decreased significantly(p<0.01) in the prickly pear cactus group compared with the control, while there was no difference in the liver levels of total cholesterol and triglyceride among groups. Fecal corprostanol and cholesterol were significantly(p<0.01) higher groups of control and prickly pear cactus compared to the other two groups. Radioisotope excretion after ingestion of 14(sup)C-cholesterol was higher in the control group than in tangerine pulp group or sea tangle group, with the highest in prickly pear group. Radioisotope excretion was the highest during the 2nd and 3rd days in all groups. Hematocrit and platelet aggregation were decreased in all fiber groups compared to the control, but not statistically different. Microscopic examination showed that cholesterol diet cause a fat accumulation in the liver and prickly pear cactus decreased the fat accumulation. Result indicates that prickly pear cactus has hypocholesterolemic effect by decreasing absorption and increasing excretion of cholesterol, thereby protective effect on fatty liver. Control group fed diet containing high cholesterol and low fiber seems to have a self control system in cholesterol absorption and excretion preventing hypercholesterolemia. (Korean J Nutrition 34(2) : 141-149, 2001)

• Journal of Haehwa Medicine
• /
• v.5 no.1
• /
• pp.185-198
• /
• 1996

After evaluation of antithrombotic effect of 40 herbs on platelet aggregation induced by ADP(Adenosine diphosphate), these results were obtained as follows: 1. Crude drugs exerting over 30 % of in Chinemys reevesii (Gray)hibition on platelet aggregation induced by ADP were Ganoderma japonicum (Fr.) Lloyd., Panax ginseng C. A. Mey., Gastrodia elata Bl., Thea sinensis, Chinemys reevesii (Gray), Cuscuta chinensis Lam., Cervus nippon Temminck., Biota orientalis (L.) Endl., Coriolus versicolor, Cinnamomum cassia Presl., Sophora flavescens Ait., Amomum villosum Lour., Carthamus tinctorius L., Rubus chingii Hu., Poria cocos (Schw.) Wolf., Laminana japonica Aresch., Ligustrum lucidum Ait., Angelica sineusis (Oliv.), Cyperus rotundas L., Ginkgo biloba L., Zingiber officinale Rosc., Prunus persica (L.) Batsch., Schizandra chinensis (Turcz.) Baill. and Plantago asiatica L.. 2. Of crude drugs having showed over 50% of inhibitory effect on platelet aggregation, at the concentration of $100{\mu}g/m{\ell}$, the inhibitory rates were 82.2% in Ganoderma japonicum (Fr.) Lloyd., 55% in Panax ginseng C. A. Mey., 50.8% in Gastrodia elata Bl., while at the concentration of $200{\mu}g/m{\ell}$, antithrombotic rates were 89.4% in Ganoderma japonicum (Fr.) Lloyd., 59.2% in Panax ginseng C. A. Mey., 57.9% in Thea sinensis, 52.7% in Gastrodia elata Bl.. These results suggest that the study sholuld be necessary on antithrombotic effect of solvent fractions of Ganoderma japonicum (Fr.) Lloyd., Panax ginseng C. A. Mey., Gastrodia elaha B1. and Thea sinensis and isolation of effective compound from above drugs.

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

• Journal of Nutrition and Health
• /
• v.46 no.4
• /
• pp.324-331
• /
• 2013

We investigated dietary effects of green tea powder (GTP) on plasma lipids, platelet aggregation, hemolysis, plasma TBARS, and liver enzymes. Thirty one volunteer diving women living on Jeju island consumed 4 g green tea powder daily for a period of four weeks and data for the study subjects were analyzed on the basis of diagnostic criteria for blood pressure (BP)(${\geq}$ 140/90 mmHg), plasma total cholesterol (TC)(${\geq}$ 200 mg/dL), and triglyceride (TG)(${\geq}$ 150mg/dL). Subjects with high BP had significantly higher TC and TG than those with normal BP. Subjects with higher TC had higher TG, and those with higher TG had lower HDL cholesterol. Platelet aggregation in the initial slope was significantly higher in subjects with normal BP, normal TC, or normal TG than their counterparts in high BP, TC, and TG. HDL cholesterol after GTP intake increased only in subject groups with normal BP, normal TC, or normal TG, and plasma TG after GTP intake decreased only in groups with higher BP, higher TG, or higher TC. Plasma TC and TG in subjects with normal BP increased after GTP intake. GTP intake caused a decrease in the initial slope of platelet aggregation in all subject groups with little effect on maximum aggregation. Total bilirubin showed a significant increase and GOT increased in all subject groups after GTP intake. Beneficial effects of short term intake of green tea powder might differ depending on the subject conditions in terms of blood pressure, plasma lipids, and other cardiovascular conditions. However, with the hypolipidemic, antithrombotic, and antioxidant actions of its bioactive flavonoids, long term usage of GTP or brewed green tea may provide preventive effects against cardiovascular disease.

• Archives of Pharmacal Research
• /
• v.28 no.1
• /
• pp.61-67
• /
• 2005

We evaluated the antiplatelet effects of two classes of ATP-sensitive potassium channel openers $(K_{ATP}\;openers)$ on washed human platelets, and the study's emphasis was on the role of mitochondrial $K_{ATP}$ in platelet aggregation. Collagen-induced platelet aggregation was inhibited in a dose dependent manner by lemakalim and SKP-450, which are potent cardio-nonselective $K_{ATP}$ openers, and also by cardioselective BMS-180448 and BMS-191095 $(IC_{50}\;:\;1,130,\;>\;1,500,\;305.3\;and\;63.9\;{\mu}M,\;respectively)$, but a significantly greater potency was noted for the cardioselective $K_{ATP}$ openers. The latter two $K_{ATP}$ openers also inhibited platelet aggregation induced by thrombin, another important blood-borne platelet activator, with similar rank order of potency $(IC_{50}\;:\;498.0\;and\;104.8{\mu}M\; for\;BMS-180448\;and\;BMS-191095,\;respectively)$. The inhibitory effects of BMS-191095 on collagen-induced platelet aggregation were significantly blocked by a 30-min pretreatment of platelets with glyburide $(1{\mu}M)$ or sodium 5-hydroxyde­canoate$(5-HD,\;100{\mu}M)$, a nonselective and selective mitochondrial $K_{ATP}$ antagonist, respectively, at similar magnitudes; this indicates the role of mitochondrial $K_{ATP}$ in the antiplatelet activity of BMS-191095. However, glyburide and 5-HD had no effect when they were added to the platelet cuvette immediately prior to the addition of BMS-191095. These findings indicate that cardioselective mitochondrial $K_{ATP}$ openers like BMS-191095 are able to exert cardioprotective effects in cardiac ischemia/reperfusion injury via dual mechanisms directed at the inhibition of platelet aggregation and the protection of cardiomyocytes, and both these mechanisms are mediated by mitochondrial$K_{ATP}$.