KMID : 0352720230470060706
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Journal of Ginseng Research 2023 Volume.47 No. 6 p.706 ~ p.713
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Anti-thrombotic effects of ginsenoside Rk3 by regulating cAMP and PI3K/MAPK pathway on human platelets
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Kwon Hyuk-Woo
Shin Jung-Hae Rhee Man-Hee Park Chang-Eun Lee Dong-Ha
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Abstract
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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 ¥áIIb¥â3 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 ¥áIIb/¥â3 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.
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KEYWORD
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G-Rk3, platelet aggregation, cyclic nucleotide, intracellular Ca2+, granule secretion
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