• Title/Summary/Keyword: Clot retraction

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20(S)-ginsenoside Rg3 inhibits glycoprotein IIb/IIIa activation in human platelets

  • Kwon, Hyuk-Woo
    • Journal of Applied Biological Chemistry
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    • v.61 no.3
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    • pp.257-265
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    • 2018
  • The Panax ginseng Mayer is used in conventional medicine in Asia owing to its preventing effects on thrombosis, hypertension, atherosclerosis, vasorelaxation and myocardial infarction. Because platelets are crucial mediators of cardiovascular diseases, many studies have investigated its functions. The previous study showed the antiplatelet effects of crude ginseng fraction and two of its components, ginsenoside Rg3 (20S and 20R). In addition, ginsenoside Rg3-enriched fraction shows an inhibitory effect on collagen-activated rat platelets. However, the mechanism underlying this effect remains unclear. Thus, I investigated the inhibitory action of ginsenoside Rg3 (20S, G-Rg3) on the regulation of signaling molecules involved in ${\alpha}IIb/{\beta}_3$ activation. I found that G-Rg3, in a cyclic AMP dependent manner, inhibited thrombin-induced activation of human platelets and affinity of fibrinogen and fibronectin with ${\alpha}IIb/{\beta}_3$. Thus, in the present study, G-Rg3 showed an inhibitory effect on glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}_3$) activation, suggesting its potential use for preventing platelet-mediated thrombotic disease.

Anti-thrombotic effects of ginsenoside Rk3 by regulating cAMP and PI3K/MAPK pathway on human platelets

  • Hyuk-Woo Kwon ;Jung-Hae Shin ;Man Hee Rhee ;Chang-Eun Park ;Dong-Ha Lee
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.706-713
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    • 2023
  • Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin αIIbβ3 using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B2 secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP3R). In the presence of G-Rk3, dense tubular system Ca2+ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β3 and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA2. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

The Inhibitory Effects of Glycyrrhiza uralensis on human Platelet Aggregation and Thrombus Formation

  • Seung Na Ko;Ji Won Son;Gyu Ri Kim;Min Seon Kim;Yea Jin Lee;Seung Ju Kim;Ji Hyeon Shin;Da In Jo;Woo Young Bok;Hye Gyo Oh;Hyuk-Woo Kwon
    • Biomedical Science Letters
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    • v.29 no.4
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    • pp.242-248
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    • 2023
  • Platelets are activated at the sites of vascular injury by a number of molecules, including adenosine diphosphate, collagen and thrombin. The full platelet aggregation is absolutely essential for the normal hemostasis. Glycyrrhiza glabra is a well-known medicinal herb that grows in various parts of the world and is known to have various effects such as antioxidant, anti-inflammatory, anti-atherogenic, anti-osteoporotic and skin-whitening. However, the platelet inhibitory effect of Glycyrrhiza glabra extract (GGE) has not been identified. In this study, we investigated if GGE inhibited platelet aggregation. We observed that GGE inhibited collagen-induced platelet aggregation, Ca2+ mobilization, and thromboxane A2 generation. In addition, GGE suppressed phosphorylation of phosphatidylinositol-3 kinase (PI3K), Akt and elevated phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3R), vasodilator stimulated phosphoprotein (VASP). Taken together, GGE showed strong antiplatelet effects and may be used to block platelet-mediated cardiovascular diseases.

Ginsenoside F4 inhibits platelet aggregation and thrombus formation by dephosphorylation of IP3RI and VASP

  • Shin, Jung-Hae;Kwon, Hyuk-Woo;Lee, Dong-Ha
    • Journal of Applied Biological Chemistry
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    • v.62 no.1
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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.

Autotransplantation of Ectopically Impacted Teeth : Two Case Reports (이소매복된 치아의 자가치아이식 증례)

  • Lim, Yuran;Kim, Jaehwan;Choi, Namki;Kim, Seonmi
    • Journal of the korean academy of Pediatric Dentistry
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    • v.44 no.1
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    • pp.108-115
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    • 2017
  • Numerous therapeutic approaches are available for impacted teeth, including orthodontic retraction, implantation, and autogenous tooth transplantation. Autotransplantation is a promising method, especially for juvenile patients, as it enables preservation of the function of the periodontal tissues, as well as continued alveolar bone growth. This report describes autotransplantation in two cases in which the tooth was fully-ectopically impacted. With case 1, an ectopically impacted premolar was extracted and transplanted in an upright position, and regenerative endodontic treatment was performed using a platelet-rich fibrin clot and mineral trioxide aggregate (MTA). With case 2, a calcifying odontogenic cyst with an impacted left mandibular second molar was treated by enucleation. The tooth was transplanted into the proper position 3 months after enucleation, and endodontic treatment was performed using MTA. In both cases, autotransplantation appeared to provide a simple and rapid treatment option for patients with ectopically impacted teeth. These cases demonstrate that autotransplantation of ectopically impacted teeth is a viable treatment option rather than implant placement or prosthesis, especially in juvenile patients.