Inhibitory Effects of Total Saponin from Korean Red Ginseng on [Ca(2+)]i Mobilization Through Phosphorylation of Cyclic Adenosine Monophosphate-dependent Protein Kinase Catalytic Subunit and Inositol 1,4,5-trisphosphate Receptor Type I in Human...

Overview

Journal J Ginseng Res

Date 2016 Feb 13

PMID 26869828

Citations 7

Authors

Jung-Hae Shin

Hyuk-Woo Kwon

Hyun-Jeong Cho

Man Hee Rhee

Hwa-Jin Park

Affiliations

Soon will be listed here.

Abstract

Background: Intracellular Ca(2+)([Ca(2+)]i) is a platelet aggregation-inducing molecule. Therefore, understanding the inhibitory mechanism of [Ca(2+)]i mobilization is very important to evaluate the antiplatelet effect of a substance. This study was carried out to understand the Ca(2+)-antagonistic effect of total saponin from Korean Red Ginseng (KRG-TS).

Methods: We investigated the Ca(2+)-antagonistic effect of KRG-TS on cyclic nucleotides-associated phosphorylation of inositol 1,4,5-trisphosphate receptor type I (IP3RI) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in thrombin (0.05 U/mL)-stimulated human platelet aggregation.

Results: The inhibition of [Ca(2+)]i mobilization by KRG-TS was increased by a PKA inhibitor (Rp-8-Br-cAMPS), which was more stronger than the inhibition by a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). In addition, Rp-8-Br-cAMPS inhibited phosphorylation of PKA catalytic subunit (PKAc) (Thr(197)) by KRG-TS. The phosphorylation of IP3RI (Ser(1756)) by KRG-TS was very strongly inhibited by Rp-8-Br-cAMPS compared with that by Rp-8-Br-cGMPS. These results suggest that the inhibitory effect of [Ca(2+)]i mobilization by KRG-TS is more strongly dependent on a cAMP/PKA pathway than a cGMP/PKG pathway. KRG-TS also inhibited the release of adenosine triphosphate and serotonin. In addition, only G-Rg3 of protopanaxadiol in KRG-TS inhibited thrombin-induced platelet aggregation.

Conclusion: These results strongly indicate that KRG-TS is a potent beneficial compound that inhibits [Ca(2+)]i mobilization in thrombin-platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic disease.

Citing Articles

Comparative antiplatelet and antithrombotic effects of red ginseng and fermented red ginseng extracts.

Irfan M, Lee Y, Lee K, Kim S, Rhee M J Ginseng Res. 2022; 46(3):387-395.

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Anti-platelet role of Korean ginseng and ginsenosides in cardiovascular diseases.

Irfan M, Kim M, Rhee M J Ginseng Res. 2020; 44(1):24-32.

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Inhibitory Effects of Ginsenoside Ro on Clot Retraction through Suppressing PI3K/Akt Signaling Pathway in Human Platelets.

Kwon H Prev Nutr Food Sci. 2019; 24(1):56-63.

PMID: 31008097 PMC: 6456239. DOI: 10.3746/pnf.2019.24.1.56.

Inhibitory effects of thromboxane A generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A phosphorylation and arachidonic acid release.

Shin J, Kwon H, Rhee M, Park H J Ginseng Res. 2019; 43(2):236-241.

PMID: 30976161 PMC: 6437639. DOI: 10.1016/j.jgr.2017.12.007.

Inhibitory Effect of 20(S)-Ginsenoside Rg3 on Human Platelet Aggregation and Intracellular Ca Levels via Cyclic Adenosine Monophosphate Dependent Manner.

Kwon H Prev Nutr Food Sci. 2019; 23(4):317-325.

PMID: 30675461 PMC: 6342537. DOI: 10.3746/pnf.2018.23.4.317.

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