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Evidence-Based Complementary and Alternative Medicine
Volume 2015 (2015), Article ID 764906, 13 pages
http://dx.doi.org/10.1155/2015/764906
Research Article

Inhibitory Effects of Cytosolic Ca2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets

1Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, 197 Inje-ro, Gimhae, Gyungnam 621-749, Republic of Korea
2Department of Biomedical Laboratory Science, Korea Nazarene University, 48 Wolbong-ro, Seobuk gu, Cheonan, Chungnam 331-778, Republic of Korea

Received 12 May 2015; Accepted 27 July 2015

Academic Editor: Hongcai Shang

Copyright © 2015 Hyuk-Woo Kwon et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Intracellular Ca2+ () is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca2+-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 μM. G-Ro inhibited strongly thrombin-elevated , which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8-Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser1756) to inhibit mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser1756) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca2+ influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser1756) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated , which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca2+-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease.