Inhibitory mechanisms of dihydroginsenoside Rg3 in platelet aggregation: Critical roles of ERK2 and cAMP

Lee, Whi Min; Kim, Sung Dae; Park, Myung Hwan; Cho, Jae Youl; Park, Hwa Jin; Seo, Geon Sik; Rhee, Man Hee

doi:10.1211/jpp/60.11.0015

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…In our previous report, we compared anti‐platelet activities of ginsenoside‐Rg3 and its derivative dihydroginsenoside‐Rg3, both of which are parent compounds of G‐Rp1. We have shown that 2H‐Rg3 was about twofold more potent than that of ginsenoside‐Rg3 (Lee et al ., 2008). Here, we demonstrated, for the first time, that another semi‐synthetic ginsenoside, derived from either ginsenoside‐Rg3 or 2H‐Rg3, has strong anti‐platelet activity, fivefold more potent than that of 2H‐Rg3 in collagen‐stimulated platelets (Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

“…Antioxidant, anti-inflammatory and anti-or pro-apoptotic activities are reported to be the possible ginseng-mediated protective mechanisms (Lu et al, 2009;Edzard, 2010). Ginseng extracts and some ginsenosides are also known to have anti-platelet activities (Hwang et al, 2008;Lee et al, 2008). However, they are relatively unstable and show low bioavailability (Tawab et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Previously, we showed that ginsenoside‐2H‐Rg3 had more potent anti‐platelet activity than its parent compound, ginsenoside‐Rg3 (Lee et al ., 2008). We also showed that G‐Rp1, another derivative of Rg3 or 2H‐Rg3, inhibits CD29‐mediated cell adhesion (Kim and Cho, 2009), LPS‐induced IL‐1β production (Kim et al ., 2009a) and metastsis (Park et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

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Ginsenoside‐Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation

Endale

Lee

Kamruzzaman

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSE Ginsenosides are the main constituents for the pharmacological effects of Panax ginseng. Such effects of ginsenosides including cardioprotective and anti‐platelet activities have shown stability and bioavailability limitations. However, information on the anti‐platelet activity of ginsenoside‐Rp1 (G‐Rp1), a stable derivative of ginsenoside‐Rg3, is scarce. We examined the ability of G‐Rp1 to modulate agonist‐induced platelet activation. EXPERIMENTAL APPROACH G‐Rp1 in vitro and ex vivo effects on agonist‐induced platelet‐aggregation, granule‐secretion, [Ca2+]i mobilization, integrin‐αIIbβ3 activation were examined. Vasodilator‐stimulated phosphoprotein (VASP) and MAPK expressions and levels of tyrosine phosphorylation of the glycoprotein VI (GPVI) signalling pathway components were also studied. G‐Rp1 effects on arteriovenous shunt thrombus formation in rats or tail bleeding time and ex vivo coagulation time in mice were determined. KEY RESULT G‐Rp1 markedly inhibited platelet aggregation induced by collagen, thrombin or ADP. While G‐Rp1 elevated cAMP levels, it dose‐dependently suppressed collagen‐induced ATP‐release, thromboxane secretion, p‐selectin expression, [Ca2+]i mobilization and αIIbβ3 activation and attenuated p38MAPK and ERK2 activation. Furthermore, G‐Rp1 inhibited tyrosine phosphorylation of multiple components (Fyn, Lyn, Syk, LAT, PI3K and PLCγ2) of the GPVI signalling pathway. G‐Rp1 inhibited in vivo thrombus formation and ex vivo platelet aggregation and ATP secretion without affecting tail bleeding time and coagulation time, respectively. CONCLUSION AND IMPLICATIONS G‐Rp1 inhibits collagen‐induced platelet activation and thrombus formation through modulation of early GPVI signalling events, and this effect involves VASP stimulation, and ERK2 and p38‐MAPK inhibition. These data suggest that G‐Rp1 may have therapeutic potential for the treatment of cardiovascular diseases involving aberrant platelet activation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ginsenoside‐Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation

Endale

Lee

Kamruzzaman

et al. 2012

British J Pharmacology

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“…In addition, Ginseng has shown a potent in vivo antithrombotic effect, which may be due to an antiplatelet activity rather than an anticoagulation activity, indicating that Ginseng intake may be beneficial for individuals with high risks of thrombosis and CVDs (Lee and Kim, 2014). In this context, the dihydro-ginsenoside Rg3 has been reported to potently inhibit platelet aggregation through the modulation of downstream intracellular signals such as cAMP and extracellular signal-regulated kinase 2 (Lee et al, 2008).…”

Section: Ginseng At the Bench: Mechanism Of Action In Cvdsmentioning

confidence: 99%

Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety

et al. 2020

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Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially lifethreatening adverse effects, and possible herb-drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the

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“…G-Rg3 suppresses blood platelet aggregation [5], thromboxane A 2 release, [Ca 2+ ] i mobilization and ATP release [6]. Furthermore, an Rg3 derivative, dihydroxyginsenoside Rg3, decreases mitogenactivated protein kinases [7]. Rg3-enriched fraction also shows inhibitory effects on collagen-induced rat platelets [8].…”

Section: Introductionmentioning

confidence: 99%

20(S)-ginsenoside Rg3 inhibits glycoprotein IIb/IIIa activation in human platelets

Kwon

2018

JABC

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The Panax ginseng Mayer is used in conventional medicine in Asia owing to its preventing effects on thrombosis, hypertension, atherosclerosis, vasorelaxation and myocardial infarction. Because platelets are crucial mediators of cardiovascular diseases, many studies have investigated its functions. The previous study showed the antiplatelet effects of crude ginseng fraction and two of its components, ginsenoside Rg3 (20S and 20R). In addition, ginsenoside Rg3-enriched fraction shows an inhibitory effect on collagen-activated rat platelets. However, the mechanism underlying this effect remains unclear. Thus, I investigated the inhibitory action of ginsenoside Rg3 (20S, G-Rg3) on the regulation of signaling molecules involved in αIIb/β 3 activation. I found that G-Rg3, in a cyclic AMP dependent manner, inhibited thrombin-induced activation of human platelets and affinity of fibrinogen and fibronectin with αIIb/β 3 . Thus, in the present study, G-Rg3 showed an inhibitory effect on glycoprotein IIb/IIIa (αIIb/β 3 ) activation, suggesting its potential use for preventing platelet-mediated thrombotic disease.

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Inhibitory mechanisms of dihydroginsenoside Rg3 in platelet aggregation: Critical roles of ERK2 and cAMP

Cited by 9 publications

References 24 publications

Ginsenoside‐Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation

Ginsenoside‐Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation

Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety

20(S)-ginsenoside Rg3 inhibits glycoprotein IIb/IIIa activation in human platelets

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