Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 30, Issue 12, Pages 2340-2344Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.30.2340
Keywords
ginkgolide C; matrix metalloproteinase-9; cyclic nucleotide; intracellular Ca2+; platelet aggregation
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In this report, we investigated the effect of ginkgolide C (GC) from Ginkgo biloba leaves in collagen (10 mu g/ml)-stimulated platelet aggregation. It has been known that matrix metalloproteinase-9 (MMP-9) is released from human platelets, and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GC to form an activated MMP-9 (86-kDa) on gelatinolytic activities. And then, GC dose-dependently inhibited platelet aggregation, intracellular Ca2+ mobilization, and thromboxane A(2) (TXA(2)) formation in collagen-stimulated platelets. In addition, GC significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have an anti-platelet function in both resting and collagen-stimulated platelets. Therefore, we demonstrate that the inhibitory effect of GC on platelet aggregation might be involved into the following pathways. GC may increase intracellular cAMP and cGMP production and MMP-9 activity, inhibit intracellular Ca2+ mobilization and TXA2 production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that GC is a potent inhibitor of collagen-stimulated platelet aggregation. It may be a suitable tool for a negative regulator during platelet activation.
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