• Journal of Ginseng Research
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• 제43권2호
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• pp.236-241
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• 2019

Background: Thromboxane A2 ($TXA_2$) induces platelet aggregation and promotes thrombus formation. Although ginsenoside Ro (G-Ro) from Panax ginseng is known to exhibit a $Ca^{2+}-antagonistic$ antiplatelet effect, whether it inhibits $Ca^{2+}-dependent$ cytosolic phospholipase $A_2$ ($cPLA_{2{\alpha}}$) activity to prevent the release of arachidonic acid (AA), a $TXA_2$ precursor, is unknown. In this study, we attempted to identify the mechanism underlying G-Ro-mediated $TXA_2$ inhibition. Methods: We investigated whether G-Ro attenuates $TXA_2$ production and its associated molecules, such as cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS), $cPLA_{2{\alpha}}$, mitogen-activated protein kinases, and AA. To assay COX-1 and TXAS, we used microsomal fraction of platelets. Results: G-Ro reduced $TXA_2$ production by inhibiting AA release. It acted by decreasing the phosphorylation of $cPLA_{2{\alpha}}$, p38-mitogen-activated protein kinase, and c-Jun N-terminal kinase1, rather than by inhibiting COX-1 and TXAS in thrombin-activated human platelets. Conclusion: G-Ro inhibits AA release to attenuate $TXA_2$ production, which may counteract $TXA_2-associated$ thrombosis.

• Journal of Applied Biological Chemistry
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• 제62권1호
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• pp.93-100
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• 2019

The root of Panax ginseng is used in ethnomedicine throughout eastern Asia and various recent studies have proved that Panax ginseng has inhibitory effects on cardiovascular disease. Each factor causing cardiovascular disease is known to have a very complex process which is achieved by a diverse number of mechanisms. Among these factors, platelets are the most important because they directly participate in thrombogenesis. Therefore, inhibiting the activity of platelets is an essential element for prevention of cardiovascular diseases. Our previous study showed the antiplatelet effects of Korean red ginseng extract and two of its components, ginsenoside Rg3 and ginsenoside Ro. However, the inhibitory mechanism of other ginsenosides remains unclear. Therefore, we investigated the inhibitory mechanism of ginsenoside F4 (G-F4) from Korean red ginseng on the regulation of signaling molecules involved in human platelet aggregation. With the use of G-F4, collagen-induced human platelet aggregation was inhibited in a dose-dependent manner, and it suppressed collagen-induced elevation of $[Ca^{2+}]_i$ mobilization through elevated phosphorylation of inositol 1, 4, 5-triphosphate receptor I ($Ser^{1756}$). In addition, G-F4 inhibited fibrinogen binding to ${\alpha}IIb/{\beta}_3$ during collagen-induced human platelet aggregation. Thus, in the present study, G-F4 showed an inhibitory effect on human platelet activation, suggesting its potential use as a new natural medicine for preventing platelet-mediated cardiovascular diseases.

• Journal of Ginseng Research
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• 제45권4호
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• pp.490-497
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• 2021

Background and objective: Synthetic ginsenoside compounds G-Rp (1,3, and 4) and natural ginsenosides in Panax ginseng 20(S)-Rg3, Rg6, F4 and Ro have inhibitory actions on human platelets. However, the inhibitory mechanism of ginsenoside Rk1 (G-Rk1) is still unclear thus, we initiated investigation of the anti-platelet mechanism by G-Rk1 from Panax ginseng. Methodology: Our study focused to investigate the action of G-Rk1 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, fibronectin adhesion, dense granule secretion, and thromboxane B2 secretion. Thrombin-induced clot retraction was also observed in human platelets. Key Results: Collagen, thrombin, and U46619-stimulated human platelet aggregation were dose-dependently inhibited by G-Rk1, while it demonstrated a more effective suppression on collagen-stimulated platelet aggregation using human platelets. Moreover, G-Rk1 suppressed collagen-induced elevation of Ca²⁺ release from endoplasmic reticulum, granule release, and α_IIbβ₃ activity without any cytotoxicity. Conclusions and implications: These results indicate that G-Rk1 possess strong anti-platelet effect, proposing a new drug candidate for treatment and prevention of platelet-mediated thrombosis in cardiovascular disease.

• Journal of Ginseng Research
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• 제45권2호
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• pp.236-245
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• 2021

Background: Red ginseng (RG) extract, especially ginsenoside Rg1 and Rb1 fractions has been reported to have antithrombotic activities. However, gastric instability and low intestinal permeability are considered to be obstacles to its oral administration. We hypothesized that stability, permeability, and activities of RG might be improved by encapsulation within nanoparticles (NPs) prepared with antithrombotic coating materials. Methods: RG-loaded chitosan (CS) NPs (PF-NPs) were prepared by complex ionic gelation with the antithrombotic wall materials, polyglutamic acid (PGA), and fucoidan (Fu). The concentrations of PGA (mg/mL, X₁) and Fu (mg/mL, X₂) were optimized for the smallest particle size by response surface methodology. Antithrombotic activities of RG and PF-NPs were analyzed using ex vivo and in vivo antiplatelet activities, in vivo carrageenan-induced mouse tail, and arteriovenous shunt rat thrombosis models. Results: In accordance with a quadratic regression model, the smallest PF-NPs (286 ± 36.6 nm) were fabricated at 0.628 mg/mL PGA and 0.081 mg/mL Fu. The inhibitory activities of RG on ex vivo and in vivo platelet aggregation and thrombosis in in vivo arteriovenous shunt significantly (p < 0.05) increased to approximately 66.82%, 35.42%, and 38.95%, respectively, by encapsulation within PF-NPs. For an in vivo carrageenan-induced mouse tail thrombosis model, though RG had a weaker inhibitory effect, PF-NPs reduced thrombus significantly due to the presence of PGA and Fu. Conclusion: PF-NPs contributed to improve the activities of RG not only by nanoencapsulation but also by antithrombotic coating materials. Therefore, PG-NPs can be suggested as an efficient delivery system for oral administration of RG.

• 대한정형외과학회지
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• 제56권5호
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• pp.450-454
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• 2021

고혈압 이외에 급성 폐쇄동맥경화증의 내과적 위험요소가 없던 75세 남자 환자가 경한 발열을 동반한 기침, 호흡 곤란으로 내원하여 코로나바이러스감염증-19 진단을 받았다. 격리입원 치료를 시작한 지 1주일째에, 우측 족부의 동통 및 저린감을 호소하기 시작하였으며, 그 다음 1주일 동안 서서히 한랭감, 전족지의 색깔 변화와 족배동맥의 소실이 나타나게 되었다. 하지 혈관조영 3차원 컴퓨터 단층촬영 검사에서 좌, 우측 모두에서 슬와동맥 이하로 전, 후경골 동맥 및 비골동맥의 혈류가 관찰되지 않았으며, 우측 총장 골동맥 내부에 혈전이 생성되어 있는 모습을 확인할 수 있었다. 우측 하지에 대하여 경피적 풍선 혈관 성형술 및 스텐트 삽입술, 항응고제 투여를 시행하였으며, 시술 직후부터 우측 족배동맥의 맥박이 온전히 촉지되고, 호소하던 한랭감이 개선되었음을 확인하였다. 혈류가 개선되었음에도 불구하고 우측 족무지의 괴사는 회복되지 않아 결국 족무지 절단술을 시행하였다.

• 대한본초학회지
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• 제28권5호
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• pp.33-38
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• 2013

Objectives : The aim of this study was to examine anti-thrombotic effect of traditional herbal extracts in a rat model of ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis. Methods : Thirty minutes prior to a 35% $FeCl_3$ application, Sprague Dawley(SD) rats were injected with the 10 types of traditional herbal extracts (100mg/kg, intraperitoneal injection), respectively. The effect of these herbal extracts was examined for time to occlusion(TTO) using the Laser doppler flow meter and measured for thrombus weight (TW) in $FeCl_3$-induced thrombosis model. Results : In the TTO, Salvia miltiorrhiza (Sm, $2.30{\pm}0.28$ min, p<0.001) and Santalum album (Sa, $2.19{\pm}0.19$ min, p<0.001) showed significantly delayed TTO more than twice compared with Saline-treated group. Cnidium officinale (Co), Psoralea corylifolia (Pc), Scutellatia baicalensis (Sba), Panax notoginseng (Pn), Angelica tenuissima (At), Scrophularia buergeriana (Sbu), Rhus verniciflua (Rv) and Picrasma quassioides (Pq), except for Rhus verniciflua (Rv) also meaningfully impeded TTO more than one fold. In addition, Salvia miltiorrhiza, Santalum album, Cnidium officinale, Psoralea corylifolia and Scutellatia baicalensis significantly reduced TW more than 10% compared with Saline-treated group. Especially, Salvia miltiorrhiza and Santalum album showed the most excellent anti-thrombotic effect among the 10 herbal extracts tested on the restoration of altered TTO and TW. Conclusions : These results suggest that Sm and Sa extracts have outstanding anti-thrombotic effect in $FeCl_3$-induced thrombosis model and is potentially useful as herbal medicines for the treatment and prevention of thrombosis.

• 대한한방부인과학회지
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• 제22권1호
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• pp.53-78
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• 2009

Purpose: In this study, we investigated the anti-thrombotic and antiinflammatory efficacy of "Gamijoukyungtang(GJKT)". Methods: We studied inhibitory effects of platelet aggregation, FXa activation, $TXB_2$ and $PGE_2$ biosynthesis and suppressive effects of GPIIb/IIIa activity and oxidative damage, pro-inflammatory cytokine reduction effects of 'GJKT(by press extractor)/GJKT-1(by pressless extractor)' in vitro. Also, we studied suppression of pulmonary embolism, AV shunt model in rats and shortening of Rat tail bleeding time in vivo. Results: GJKT/GJKT-1 extract showed inhibitory effects on GPIIb/IIIaactivities and platelet aggregation induced by ADP, epinephrine, collagen and arachidonic acid. They suppressed biosynthesis of $PGE_2$ but GJKT-1 only supressed biosynthesis of $TXB_2$. In FXa assay, they inhibited activation of FXa. they suppressed pulmonary embolism triggered by collagen and epinephrine. In AV shunt model, they decreased the weights of AV shunt thrombus. they inhibited pro-inflammatory cytokines and decreased oxidative damages caused by DPPH. Conclusion: We confirmed the anti-thrombosis, and ant-inflammatory efficacy of 'GJKT(by press extractor)/GJKT-1(by pressless extractor)'.

• Journal of Korean Neurosurgical Society
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• 제66권6호
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• pp.735-742
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• 2023

Nephrotic syndrome (NS) is associated with cerebral venous sinus thrombosis (CVST), which is a rare cerebrovascular disorder in children. Systemic anticoagulation with heparin is the standard therapy for CVST, and mechanical thrombectomy (MT) has been described as a salvage treatment for adult anticoagulant refractory CVST, However, it has never been reported in children. We describe a case of MT for refractory CVST in a child with NS. A 13-year-old boy with newly diagnosed NS presented to an emergency department with acute headache. A head computed tomography showed acute thrombus in the superior sagittal sinus, straight sinus and transverse sinus. The child was started on heparin therapy, but clinically deteriorated and became unresponsive. In view of the rapid deterioration of the condition after anticoagulation treatment, the patient received intravascular treatment. Several endovascular technologies, such as stent retriever and large bore suction catheter have been adopted. After endovascular treatment, the patient's neurological condition was improved within 24 hours, and magnetic resonance venography of the head demonstrated that the CVST was reduced. The child recovered with normal neurological function at discharge. This case highlights the importance of considering MT for refractory CVST, and we suggest that MT may be considered for refractory CVST with NS in children.

• 대한한방내과학회지
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• 제44권5호
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• pp.999-1010
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• 2023

This case report shows the effect of Korean medicine treatment in a patient with deep vein thrombosis (DVT) after cerebral infarction who is suspected of having post-thrombotic syndrome (PTS) due to the loss of thrombus after receiving new oral anticoagulant (NOAC) treatment. The patient was treated with Korean medicine (Boyanghwano-tang and Hyulbuchuko-tang) three times a day. Acupuncture, moxibustion, infrared, and extra-physical therapy were given to the patient for 24 days. Clinical assessment - grading of edema and circumference of the left lower extremity were observed twice a week until the end of the treatment. NOAC treatment was continued for 24 days. After treatment, the patient's edema grade and circumference of the extremity improved. On the 24th day, the patient's chief complaints improved, and she requested termination of treatment. The results suggest that Korean medicine treatments, including Boyanghwano-tang, Hyulbuchuko-tang, and acupuncture therapy, can be effective in improving the clinical symptoms of DVT and PTS.

• Korean Circulation Journal
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• 제53권8호
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• pp.566-577
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• 2023

Background and Objectives: The left atrial appendage (LAA) can contribute significantly to LA mechanical contraction. Nevertheless, the preventive effect of LAA occlusion during the maze procedure against cerebral infarction remains controversial. In this study, we compared the surgical, cardiac hemodynamic, and neurologic outcomes between LAA preservation and occlusion performed during the maze procedure. Methods: Between January 2015 and August 2021, 252 patients underwent the maze procedure using cryoablation at our medical center. After excluding patients according to our exclusion criteria (i.e., mechanical prosthesis implantation, preexisting LAA thrombus), LAA was preserved in 113 patients (non-occlusion group) and occluded in 75 patients (occlusion group). Outcomes were compared using propensity score matching (PSM). Results: PSM did not reveal significant intergroup differences in baseline characteristics between the non-occlusion (n=53) and occlusion (n=53) groups. During a median follow-up of 44 months, 2 patients in the non-occlusion group (3.8%) experienced ischemic strokes. There was no significant difference in the rate of freedom from stroke (p=0.19) and major adverse cardiac events (p=0.43) between the 2 groups. Through echocardiography at 1-year follow-up, a statistically significant difference in LA mechanical contraction was observed between the non-occlusion group and occlusion group (24 of 33 [72.7%] vs. 18 of 37 [48.6%], respectively; p=0.04). Conclusions: In this study, preservation of the LAA during the maze procedure resulted in better LA function than LAA occlusion, with similar rates of stroke.