• 생약학회지
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• 제52권1호
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• pp.26-33
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• 2021

During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.

• 한국산학기술학회논문지
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• 제20권12호
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• pp.298-305
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• 2019

꾸지뽕나무 뿌리 추출물은 항염, 항암, 항산화와 같은 효과를 갖는 많은 생리활성 물질을 포함하고 있다고 알려져 있다. 그러나 꾸지뽕나무 뿌리 추출물(이하 CTE)의 사람 혈소판 응집 억제 기전에 관하여는 알려진 바 없다. 본 연구에서는 CTE가 혈소판에 미치는 영향을 확인하고자 하였다. CTE는 collagen으로 유도한 혈소판 응집 반응에서 cyclooxygenase-1 활성을 억제하고, 세포 내 칼슘 농도를 낮추는 방식으로 thromboxane A₂ 생성을 억제하였다. 또한, phospholipase Cγ2와 syk의 인산화 반응을 억제하였으며, guanosine monophosphate (cGMP)에 의존적인 방식으로 vasodilator-stimulated phosphoprotein(VASP)의 Ser²³⁹ 위치를 인산화하여 항혈소판 효과를 나타내었다. 또한, 고지방 식이로 혈소판 활성화를 유도한 랫드에서 CTE를 경구 투여 하였을 때, 간독성 없이 콜라겐으로 유도한 혈소판 응집반응을 thromboxane A₂ 생성을 억제함으로써 항혈소판 효과를 보였다. 이는 in vivo와 in vitro에서 같은 결과를 제시하고 있다. 결론적으로, CTE는 항혈소판 작용 및 심혈관계 질환 예방을 위한 천연물 유래의 안전하고, 새로운 물질임을 제시하는 바이다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.380.3-380.3
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• 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)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.336.2-336.2
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• 2002

Several 1 A-naphthoquinone derivatives have been reported to possess many pharmacological effects such as anti-viral. anti-fungal. anti-cancer and anti-platelet activities. We have reported that 2-chloro-3-［4-(ethyICarbOxy)-phenyl］-amino-1.4-naphthoquinone(NQ12) had a potent inhibitory effect on the platelet aggregation in vitro and thrombosis in vivo. However. little has been known about functional roleot NQ12 on vascular smooth muscle cells (VSMCs). (omitted)

• 대한한방부인과학회지
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• 제21권1호
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• pp.117-133
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• 2008

Purpose: This study was performed to evaluate anti-thrombotic effects of Hyulbuchukeotanggamibang(HBCT). Methods: It was measured the effects which was given to blood flow rate through the regular volume of glass tube after the blood was diluted five times with ACD soulution. Antithrombotic effect was calculated as a percentage of the experimental animal figure protected from the paralysis of hind legs or death of the mouse that is caused from the administration of platelet aggregation regent. Results: 1. HBCT showed a safety in toxicity of liver. 2. In experiment of anti-thrombotic effect, HBCT inhibited the platelet aggregation induced by ADP and epinephrine, collagen, arachidonic acid as compared with the control group. 3. HBCT inhibited pulmonary embolism induced by collagen and epinephrine (inhibitory rate is 50%). 4. HBCT increased platelet number and fibrinogen amount significantly and also HBCT shortened PT and APTT significantly as compared with the control group in thrombus model induced by dextran. 5. HBCT increased blood flow rate insignificantly as compared with the control group in vivo. Conclusion: These results suggest that HBCT can be used for treating diverse female diseases caused by thrombosis.

• 한국한의학연구원논문집
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• 제11권2호
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• pp.97-111
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• 2005

This study was performed to evaluate anti-thrombotic activities and anti-inflammatory effects of ChungyeolHaedogHwaeoTang water extract(CHHT). The results were summarized as follows. In experiment of anti-thrombotic effect; 1. CHHT inhibited human platelet aggregation induced by ADP and epinephrine as compared with the control group, and inhibited pulmonary embolism induced by collagen and epinephrine (inhibitory rate is 37.5%). 2. CHHT increased platelet number significantly, and also CHHT shortened PT and APTT significantly as compared with the control group in thrombus model induced by dextran. In experiment of anti-inflammatory effect; 3. CHHT inhibited $IL-1{\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II mRNA expression as compared with the control group in a concentration-dependent degree, and inhibited NO production significantly at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent degree as compared with the control of group in RAW 264.7 cell line. 4. CHHT inhibited $IL-1{\beta}$, IL-6 and TNF-${\alpha}$ production significantly in serum of acute inflammation-induced mice, and decreased $IL-1{\beta}$, IL-6 and TNF-${\alpha}$ production in spleen tissue, and also decreased $IL-1{\beta}$, and IL-6 production in liver tissue, but increased TNF-${\alpha}$ production in liver tissue of acute inflammation-induced Balb/c mice. 5. CHHT increased survival rate from the 3rd day in ICR mice with lethal endotoxemia induced by LPS. These results suggest that CHHT can be useful in treating diverse female diseases caused by thrombosis and inflammation such as menstrual pain, menstrual disorder, leukorrhea, vaginitis, cervicitis, pelvic inflammatory disease and so on.

• Nutrition Research and Practice
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• 제8권5호
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• pp.521-525
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• 2014

BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through $H_2DCF$-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT ($10{\mu}M$ and $30{\mu}M$) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT ($10{\mu}M$ and $30{\mu}M$) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.

• 대한한방부인과학회지
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• 제20권3호
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• pp.45-64
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• 2007

Purpose: This study was performed to evaluate anti-thrombotic and anti-inflammatory effects of NeungaSoJeokTang water extract (NSJT). Methods: In the study of anti-inflammatory effects, NSJT was investigated using cultured cells and murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells(mLFC) and RAW 264.7 cells. Results: Prior to the experiment, we evaluated sGOT, sGPT, BUN and creatine after the treatment. As a result, NSJT was innoxious on liver and kidney. In experiment of anti-thrombotic effect, NSJT inhibited the platelet aggregation induced by ADP and epinephrine, and inhibited pulmonary embolism induced by collagen and epinephrine. NSJT did not affect significantly the blood flow rate both in vitro and in vivo. NSJT increased platelet number and fibrinogen amount, and NSJT shortened PT and APTT in thrombus model induced by dextran. In experiment of anti-inflammatory effect, NSJT inhibited $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2 and NOS-II mRNA expression in a concentration-dependent manner in RAW 264.7 cell line, and inhibited significantly NO production at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent manner. NSJT inhibited $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production significantly in serum of acute inflammation-induced Balb/c mice, and decreased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in spleen tissue, but increased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in liver tissue. NSJT increased survival rate at the 3th day in ICR mice with lethal endotoxemia induced by LPS. Conclusion: These results suggest that NSJT can be used for treating diverse female diseases caused by thrombosis and inflammation such as pelvic pain, pelvic inflammatory disease as well as vulvar pain due to vulvitis, vulvar vestibulitis and so on.

• 생약학회지
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• 제53권2호
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• pp.64-69
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• 2022

When blood vessels are damaged, a rapid hemostatic response should occur in order to lower blood loss and keep normal circulation, and platelet activation and aggregation are essential. Nevertheless, abnormal or excessive platelet aggregation can be a reason of cardiovascular diseases including thrombosis, atherosclerosis, and stroke. Therefore, the screening for a substance which can regulate platelet activation and suppress aggregation reaction is very important for treatment and prevention of cardiovascular diseases. Artemether is a methyl ether derivative of artemisinin, which is isolated from the antimalarial plant Artemisia annua, but research on platelet aggregation or its mechanisms is still insufficient. This study identified the effects of artemether on U46619-induced human platelet aggregation and their granule secretion (ATP and serotonin release). In addition, the effects of artemether on the phosphorylation of PI3K/Akt or MAPK, which are related to signal transduction in platelet aggregation, were studied. As the results, artemether significantly lowered PI3K/Akt and MAPK phosphorylation, which inhibited platelet aggregation through granule secretion (ATP and serotonin release) dose-dependently. Therefore, we suggest that artemether is an antiplatelet substance that regulates PI3K/Akt and MAPK pathway and is of value as a therapeutic and preventive agent for platelet-derived cardiovascular diseases.

• 대한한방내과학회지
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• 제18권1호
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• pp.69-85
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• 1997

This study was designed to elucidate the anti-inflammatory, cardiovascular, anti-thrombotic and analgesic effects of Shintongchugeotang. The anti-inflammatory effect was measured by the method of carragenin induced edema, protein leakage test using CMC-pouch, and the analgesic effect was measured by the acetic acid method and hot plate method, and the effect of Shintongchugeotang on the cardiovascular system was observed by the change of flow rate of Ringer solution in the vascular system in the ear of rabbit, and the contraction and dilatation of rat tail artery. Death rate, platelet aggregation, plasma coagulation activity was observed for the measurement of the anti-coagurative effect of Shintongchugeotang. The result was as follows : 1. After the administration of Shintongchugeotang extract, Carragenin induced edema and CMC-pouch protein leakage were significantly decreased. 2. The slight analgesic effect of Shintongchugeotang extract was confirmed by the observation of writhing syndrome, paw licking time, and escape time. 3. The drug increased the auricular blood flow in rabbit. 4. The drug relaxed the artery contraction by pretreated norepinephrine in rat. 5. The drug inhibited the death rate of mouse which was led to thromboembolism by serotonin and collagen. 6. The drug inhibited the platelet aggregation in rat. 7. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable.