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Platelets. 2019;30(5):589-598. doi: 10.1080/09537104.2018.1479033. Epub 2018 Jun 5.

Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling.

Author information

1
a Laboratory of Physiology and Cell Signaling, College of Veterinary Medicine , Kyungpook National University , Daegu , Republic of Korea.
2
b Department of Biomedical Laboratory Science , Far East University , Eumseong , Korea.
3
c Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering , Inje University , Gyungnam , Korea.
4
d Institute of Animal Medicine, College of Veterinary Medicine , Gyeongsang National University , Jinju , Republic of Korea.
5
e Department of Biomedical Laboratory Science , Korea Nazarene University , Cheonan, Chungnam , Republic of Korea.
6
f Molecular Diagnostics Research Institute , Namseoul University , Cheonan, Chungnam , Republic of Korea.
7
g Ginsentology Research Laboratory, Department of Physiology, College of Veterinary Medicine , Konkuk University , Seoul , Republic of Korea.

Abstract

Panax ginseng (P. ginseng), one of the most valuable medicinal plants, is known for its healing and immunobooster properties and has been widely used in folk medicine against cardiovascular diseases, including stroke and heart attack. In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIbβ3 activation, and intracellular calcium ion ([Ca2+]i) mobilization were examined. Western blot analysis and immunoprecipitation techniques were used to estimate the expression of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and interaction of glycoprotein VI (GPVI) signaling pathway molecules such as Src family kinases (SFK), tyrosine kinase Syk, and PLCγ2. In vivo effects were studied using acute pulmonary thromboembolism model in mice. Gintonin remarkably inhibited collagen-induced platelet aggregation and suppressed granule secretion, [Ca2+]i mobilization, and fibrinogen binding to integrin αIIbβ3 in a dose-dependent manner and clot retraction. Gintonin attenuated the activation of MAPK molecules and PI3K/Akt pathway. It also inhibited SFK, Syk, and PLCγ2 activation and protected mice from thrombosis. Gintonin inhibited agonist-induced platelet activation and thrombus formation through impairment in GPVI signaling molecules, including activation of SFK, Syk, PLCγ2, MAPK, and PI3K/Akt; suggesting its therapeutic potential against platelet related CVD.

KEYWORDS:

; Anti-thrombotic agent; GPVI signaling; gintonin; platelets; thrombosis

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