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标题：Ginkgolide C Inhibits Platelet Aggregation in cAMP- and cGMP-Dependent Manner by Activating MMP-9
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作者：Hyun-Jeong Cho ; Yun-Hee Shon ; Kyung-Soo Nam 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：12
页码：2340-2344
DOI：10.1248/bpb.30.2340
出版社：The Pharmaceutical Society of Japan
摘要：In this report, we investigated the effect of ginkgolide C (GC) from Ginkgo biloba leaves in collagen (10 μg/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 A₂ (TXA₂) 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.
关键词：ginkgolide C;matrix metalloproteinase-9;cyclic nucleotide;intracellular Ca2+;platelet aggregation