Metabolomic Investigation of the Anti-Platelet Aggregation Activity of Ginsenoside Rk1 Reveals Attenuated 12-HETE Production
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- 作者：Hyun Kyoung Ju ; Jin Gyun Lee ; Mi Kyung Park ; So-Jung Park ; Chang Hoon Lee ; Jeong Hill Park ; Sung Won Kwon
- 刊名：Journal of Proteome Research
- 出版年：2012
- 出版时间：October 5, 2012
- 年：2012
- 卷：11
- 期：10
- 页码：4939-4946
- 全文大小：424K
- 年卷期：v.11,no.10(October 5, 2012)
- ISSN：1535-3907
文摘
Comprehensive metabolomics analysis is an effective method of measuring metabolite levels in the body following administration of a pharmaceutical compound and can allow for monitoring of the effects of the compound or assessment of appropriate treatment options for individual patients. In the present metabolomics study, samples pretreated with antiplatelet compounds were extracted and subjected to ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. The acquired data were processed using peak clustering and evaluated by partial least-squares (PLS) and orthogonal projections to latent structures discriminant analyses (OPLS-DA). As a result, meaningful endogenous metabolites, namely eicosanoids and thromboxane B2 (TXB2), were identified. TXB2, a key element in platelet aggregation, was decreased upon ginsenoside Rk1 treatment via inhibition of cyclooxygenase (COX) activity. One of the arachidonic acid (AA) metabolites, 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), was decreased significantly in the ginsenoside Rk1-treated platelets compared to the AA-induced group. In the mechanism study of ginsenoside Rk1, a strong linkage to intracellular calcium levels, which induce platelet activation, was found. Additionally, the translocation of 12-LOX from cytosol to membrane, which is related with the intracellular calcium levels, was determined. Therefore, a decreased 12-HETE level induced by ginsenoside Rk1 on antiplatelet aggregation is related to 12-LOX translocation resulting from decreased Ca2+ levels. This study shows that global metabolomic analysis has potential for use in understanding the biological behavior of antiplatelet drugs.