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Ginsenoside‐Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation
Author(s) -
Endale M,
Lee WM,
Kamruzzaman SM,
Kim SD,
Park JY,
Park MH,
Park TY,
Park HJ,
Cho JY,
Rhee MH
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2012.01967.x
Subject(s) - platelet activation , chemistry , microbiology and biotechnology , thromboxane a2 , tyrosine phosphorylation , phosphorylation , mapk/erk pathway , platelet , pharmacology , biochemistry , medicine , biology , receptor
BACKGROUND AND PURPOSE Ginsenosides are the main constituents for the pharmacological effects of Panax ginseng . Such effects of ginsenosides including cardioprotective and anti‐platelet activities have shown stability and bioavailability limitations. However, information on the anti‐platelet activity of ginsenoside‐Rp1 (G‐Rp1), a stable derivative of ginsenoside‐Rg3, is scarce. We examined the ability of G‐Rp1 to modulate agonist‐induced platelet activation. EXPERIMENTAL APPROACH G‐Rp1 in vitro and ex vivo effects on agonist‐induced platelet‐aggregation, granule‐secretion, [Ca 2+ ] i mobilization, integrin‐α IIb β 3 activation were examined. Vasodilator‐stimulated phosphoprotein (VASP) and MAPK expressions and levels of tyrosine phosphorylation of the glycoprotein VI (GPVI) signalling pathway components were also studied. G‐Rp1 effects on arteriovenous shunt thrombus formation in rats or tail bleeding time and ex vivo coagulation time in mice were determined. KEY RESULT G‐Rp1 markedly inhibited platelet aggregation induced by collagen, thrombin or ADP. While G‐Rp1 elevated cAMP levels, it dose‐dependently suppressed collagen‐induced ATP‐release, thromboxane secretion, p‐selectin expression, [Ca 2+ ] i mobilization and α IIb β 3 activation and attenuated p38 MAPK and ERK2 activation. Furthermore, G‐Rp1 inhibited tyrosine phosphorylation of multiple components (Fyn, Lyn, Syk, LAT, PI3K and PLCγ2) of the GPVI signalling pathway. G‐Rp1 inhibited in vivo thrombus formation and ex vivo platelet aggregation and ATP secretion without affecting tail bleeding time and coagulation time, respectively. CONCLUSION AND IMPLICATIONS G‐Rp1 inhibits collagen‐induced platelet activation and thrombus formation through modulation of early GPVI signalling events, and this effect involves VASP stimulation, and ERK2 and p38 ‐MAPK inhibition. These data suggest that G‐Rp1 may have therapeutic potential for the treatment of cardiovascular diseases involving aberrant platelet activation.