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. 2019 Apr;43(2):236-241.
doi: 10.1016/j.jgr.2017.12.007. Epub 2018 Jan 9.

Inhibitory effects of thromboxane A2 generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A2 phosphorylation and arachidonic acid release

Jung-Hae Shin  1 , Hyuk-Woo Kwon  2 , Man Hee Rhee  3 , Hwa-Jin Park  1
Affiliations

Inhibitory effects of thromboxane A2 generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A2 phosphorylation and arachidonic acid release

Jung-Hae Shin et al. J Ginseng Res. 2019 Apr.

Abstract

Background: Thromboxane A2 (TXA2) induces platelet aggregation and promotes thrombus formation. Although ginsenoside Ro (G-Ro) from Panax ginseng is known to exhibit a Ca2+-antagonistic antiplatelet effect, whether it inhibits Ca2+-dependent cytosolic phospholipase A2 (cPLA2α) activity to prevent the release of arachidonic acid (AA), a TXA2 precursor, is unknown. In this study, we attempted to identify the mechanism underlying G-Ro-mediated TXA2 inhibition.

Methods: We investigated whether G-Ro attenuates TXA2 production and its associated molecules, such as cyclooxygenase-1 (COX-1), TXA2 synthase (TXAS), cPLA2α, mitogen-activated protein kinases, and AA. To assay COX-1 and TXAS, we used microsomal fraction of platelets.

Results: G-Ro reduced TXA2 production by inhibiting AA release. It acted by decreasing the phosphorylation of cPLA2α, p38-mitogen-activated protein kinase, and c-Jun N-terminal kinase1, rather than by inhibiting COX-1 and TXAS in thrombin-activated human platelets.

Conclusion: G-Ro inhibits AA release to attenuate TXA2 production, which may counteract TXA2-associated thrombosis.

Keywords: Arachidonic acid; Cytosolic phospholipase A2α; Ginsenoside Ro; Mitogen-activated protein kinases; Thromboxane A2.

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Figures

Fig. 1
Fig. 1
Effects of G-Ro on thrombin-induced human platelet aggregation and thromboxane B2 production. (A) Structure of G-Ro. (B) Effect of G-Ro on thrombin-induced human platelet aggregation. (C) Effect of G-Ro on thromboxane B2 production. Platelet aggregation and thromboxane B2 production were carried out as described in “Materials and methods” section. The data are expressed as the mean ± standard deviation (n = 4). ∗p < 0.05 versus the thrombin-stimulated human platelets, ∗∗p < 0.01 versus the thrombin-stimulated human platelets.
Fig. 2
Fig. 2
Effects of G-Ro on COX-1 and TXAS activities. (A) Determination of the effects of the enzyme sources on COX-1 and TXAS activities. (B) Determination of the effects of G-Ro on COX-1. (C) Determination of the effects of G-Ro on TXAS activities. Western blot analysis and COX-1 and TXAS activities were determined as described in “Materials and methods” section. The data are expressed as the mean ± standard deviation (n = 4). ∗p < 0.05 versus the thrombin-stimulated human platelets.
Fig. 3
Fig. 3
Effects of G-Ro on cPLA2α-phosphorylation and AA release. (A) Effects of G-Ro on cPLA2-phosphorylation. (B) Effects of G-Ro on AA release. Western blot and AA release assay were determined as described in “Materials and methods” section. The data are expressed as the mean ± standard deviation (n = 3). ∗p < 0.05 versus the thrombin-stimulated human platelets, ∗∗p < 0.01 versus the thrombin-stimulated human platelets.
Fig. 4
Fig. 4
Effects of G-Ro on the phosphorylation of MAPKs. (A) Effects of G-Ro on the phosphorylation of p38-MAPK. (B) Effects of G-Ro on JNK1/2 phosphorylation. Western blot was determined as described in “Materials and methods” section. The data are expressed as the mean ± standard deviation (n = 3). ∗p < 0.05 versus the thrombin-stimulated human platelets, ∗∗p < 0.01 versus the thrombin-stimulated human platelets.
Fig. 5
Fig. 5
Effects of MAPK inhibitors on cPLA2α-phosphorylation, AA release, and TXA2 production. (A) Effects of MAPK inhibitors on cPLA2-phosphorylation. (B) Effects of SB203580 on AA release. (C) Effects of SB203580 on TXA2 production. Western blot, AA release assay, and TXA2 production were determined as described in “Materials and methods” section. The data are expressed as the mean ± standard deviation (n = 3). ∗p < 0.05 versus the thrombin-stimulated human platelets in the presence of 0.1% DMSO, ∗∗p < 0.01 versus the thrombin-stimulated human platelets in the presence of 0.1% DMSO.
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