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Inhibitory Effects of Cytosolic Ca(2+) Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets.

Kwon HW, Shin JH, Lee DH, Park HJ - Evid Based Complement Alternat Med (2015)

Bottom Line: This study was carried out to understand the Ca(2+)-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng.Phosphorylation of IP3RI (Ser(1756)) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS.We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser(1756)) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca(2+)] i , which contributes to inhibition of ATP and serotonin release, and p-selectin expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, 197 Inje-ro, Gimhae, Gyungnam 621-749, Republic of Korea.

ABSTRACT
Intracellular Ca(2+) ([Ca(2+)] i ) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca(2+)-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 [Ca(2+)] i , 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) (Ser(1756)) to inhibit [Ca(2+)] i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser(1756)) 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 Ca(2+) influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser(1756)) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca(2+)] i , 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 Ca(2+)-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of ginsenoside Ro. Ginsenoside Ro (G-Ro), an oleanane-type saponin, is contained in Panax ginseng Meyer [19, 20] and is composed of oleanolic acid as aglycone and two glucose and one glucuronic acid as sugar component [19].
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Related In: Results  -  Collection


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fig1: Chemical structure of ginsenoside Ro. Ginsenoside Ro (G-Ro), an oleanane-type saponin, is contained in Panax ginseng Meyer [19, 20] and is composed of oleanolic acid as aglycone and two glucose and one glucuronic acid as sugar component [19].

Mentions: Ginseng, the root of Panax ginseng Meyer, has been used frequently in traditional oriental medicine and is known to have various pharmacological activities such as anti-inflammatory action, antioxidation, antitumor, antidiabetes, and antihepatotoxicity [21, 22]. In recent, it is reported that Korean red ginseng has an effect on cardiovascular disease, which is characterized with regard to reduction of blood pressure and arterial stiffness by inhibition of Rho kinase [23], anticoagulation by prolonged prothrombin and activated partial thromboplastin time [24], endothelium relaxation by nitric oxide-cGMP pathway [25], and inhibition of hypercholesterolemia-induced platelet aggregation [26]. In our previous report, we demonstrated that total saponin from Korean red ginseng (TSKRG) is a beneficial traditional oriental medicine in platelet-mediated thrombotic disease via suppression of cyclooxygenase-1 (COX-1) and thromboxane A2 synthase (TXAS) to inhibit production of thromboxane A2 (TXA2) [27]. It is reported that ginsenoside Ro (G-Ro, Figure 1) has no inhibitory effect on collagen-elevated [Ca2+]i [28]. However, in this study, we showed that G-Ro attenuates thrombin-elevated [Ca2+]i via cAMP-dependent IP3RI phosphorylation and dephosphorylation of ERK in human platelets. This study provides novel information for antiplatelet effects of G-Ro in ginseng.


Inhibitory Effects of Cytosolic Ca(2+) Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets.

Kwon HW, Shin JH, Lee DH, Park HJ - Evid Based Complement Alternat Med (2015)

Chemical structure of ginsenoside Ro. Ginsenoside Ro (G-Ro), an oleanane-type saponin, is contained in Panax ginseng Meyer [19, 20] and is composed of oleanolic acid as aglycone and two glucose and one glucuronic acid as sugar component [19].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4556879&req=5

fig1: Chemical structure of ginsenoside Ro. Ginsenoside Ro (G-Ro), an oleanane-type saponin, is contained in Panax ginseng Meyer [19, 20] and is composed of oleanolic acid as aglycone and two glucose and one glucuronic acid as sugar component [19].
Mentions: Ginseng, the root of Panax ginseng Meyer, has been used frequently in traditional oriental medicine and is known to have various pharmacological activities such as anti-inflammatory action, antioxidation, antitumor, antidiabetes, and antihepatotoxicity [21, 22]. In recent, it is reported that Korean red ginseng has an effect on cardiovascular disease, which is characterized with regard to reduction of blood pressure and arterial stiffness by inhibition of Rho kinase [23], anticoagulation by prolonged prothrombin and activated partial thromboplastin time [24], endothelium relaxation by nitric oxide-cGMP pathway [25], and inhibition of hypercholesterolemia-induced platelet aggregation [26]. In our previous report, we demonstrated that total saponin from Korean red ginseng (TSKRG) is a beneficial traditional oriental medicine in platelet-mediated thrombotic disease via suppression of cyclooxygenase-1 (COX-1) and thromboxane A2 synthase (TXAS) to inhibit production of thromboxane A2 (TXA2) [27]. It is reported that ginsenoside Ro (G-Ro, Figure 1) has no inhibitory effect on collagen-elevated [Ca2+]i [28]. However, in this study, we showed that G-Ro attenuates thrombin-elevated [Ca2+]i via cAMP-dependent IP3RI phosphorylation and dephosphorylation of ERK in human platelets. This study provides novel information for antiplatelet effects of G-Ro in ginseng.

Bottom Line: This study was carried out to understand the Ca(2+)-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng.Phosphorylation of IP3RI (Ser(1756)) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS.We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser(1756)) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca(2+)] i , which contributes to inhibition of ATP and serotonin release, and p-selectin expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, 197 Inje-ro, Gimhae, Gyungnam 621-749, Republic of Korea.

ABSTRACT
Intracellular Ca(2+) ([Ca(2+)] i ) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca(2+)-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 [Ca(2+)] i , 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) (Ser(1756)) to inhibit [Ca(2+)] i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser(1756)) 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 Ca(2+) influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser(1756)) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca(2+)] i , 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 Ca(2+)-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease.

No MeSH data available.


Related in: MedlinePlus