Cordycepin (3′-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP- and cyclic GMP-dependent manner

Cho, Hyun-Jeong; Cho, Jae Youl; Rhee, Man Hee; Park, Hwa-Jin

doi:10.1016/j.ejphar.2006.11.073

Cited by 68 publications

(55 citation statements)

References 40 publications

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“…Moreover, previous investigators have reported that cordyceps inhibits the proliferation of various cells, including cancer cells, in vitro (18). It has been reported that cordycepin stimulates cAMP and cGMP production in platelets (19,20). Recently, it has also been shown that cordycepin inhibits the migration and proliferation of VSMC and vascular neointima formation (21).…”

Section: Introductionmentioning

confidence: 99%

Cordycepin Attenuates Neointimal Formation by Inhibiting Reactive Oxygen Species–Mediated Responses in Vascular Smooth Muscle Cells in Rats

Won

Lee

et al. 2009

J Pharmacol Sci

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Abstract. We determined the action mechanism of cordycepin, a major bioactive component of Cordyceps militaris, on responses of rat aortic smooth muscle cells (RASMCs) and on vascular disorders, especially neointimal formation. Cordycepin inhibited platelet-derived growth factor-BB (PDGF-BB)-induced RASMCs migration and proliferation in a dose-dependent manner. However, pre-treatment with N ω -nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor, and 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), an A 1 / A 2 adenosinereceptor antagonist, abolished the inhibitory role of cordycepin. Cordycepin suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and heat shock protein 27 (Hsp27), but not that of extracellular signal-regulated kinase (ERK) 1/2 in RASMCs stimulated by PDGF-BB. The production of reactive oxygen species (ROS), O 2 − and H 2 O 2 , induced by PDGF-BB was abolished by the treatment of cordycepin. Moreover, the sprout outgrowth of aortic rings by PDGF-BB was inhibited by cordycepin. In vivo neointimal formation evoked by balloon-injury was significantly attenuated by the administration of cordycepin. These results demonstrate that cordycepin may exert inhibitory effects on PDGF-BB-induced migration and proliferation via interfering with adenosine receptor-mediated NOS pathways, thus resulting in the attenuation of neointima formation. In conclusion, cordycepin may be a potent, promising anti-atherosclerosis agent.

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Section: Introductionmentioning

confidence: 99%

Cordycepin Attenuates Neointimal Formation by Inhibiting Reactive Oxygen Species–Mediated Responses in Vascular Smooth Muscle Cells in Rats

Won

Lee

et al. 2009

J Pharmacol Sci

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“…PDE 2 hydrolyzes both cAMP and cGMP as cGMP-stimulated PDE, PDE 3 hydrolyzes cAMP rather than cGMP as cGMPinhibited PDE, and PDE 5 hydrolyzes cGMP only as cGMPbinding-cGMP specific PDE. Because cordycepin increased both cAMP and cGMP in collagen-induced platelet aggregation, although it is thought that cordycepin might involve inhibition of PDE 2 to increase both cAMP and cGMP, we cannot exclude that cordycepin might involve activation of adenylate cyclase to produce cAMP from ATP, because cordycepin-elevated cAMP level was decreased by adenylate cyclase inhibitor SQ22536 (Cho et al, 2007). Nieswandt group provided an evidence for cross-talk between collagen receptor GPVI and G i -coupled receptor during collageninduced platelet aggregation (Nieswandt et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

“…(Pasqui et al, 1991). Because cordycepin did not produce NO in platelets (Cho et al, 2007), the elevation of cGMP achieved by cordycepin is independent on NO/guanylate cyclase pathway. level in the presence of both collagen and cordycepin was 217.2 ± 3.6 nM, which was significantly elevated by PKA inhibitor Rp-8-Br-cAMPS to 283.9 ± 8.2 nM (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Inhibitory Effects of Cordycepin on Platelet ActivationviaRegulation of Cyclic Adenosine Monophosphate-downstream Pathway

Lee

2017

BSL

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Platelet activation is essential at the sites of vascular injury, which leads to hemostasis through adhesion, aggregation, and secretion process. However, potent and continuous platelet activation may be an important reason of circulatory disorders. Therefore, proper regulation of platelet activation may be an effective treatment for vascular diseases. In this research, inhibitory effects of cordycepin (3'-deoxyadenosine) on platelet activation were determined. As the results, cordycepin increased cAMP and cGMP, which are intracellular Ca 2+ -antagonists. In addition, cordycepin reduced collagenelevated [Ca 2+ ] i mobilization, which was increased by a cAMP-dependent protein kinase (PKA) inhibitor (Rp-8-BrcAMPS), but not a cGMP-protein kinase (PKG) inhibitor ) phosphorylation was inhibited by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS, and cordycepin inhibited collagen-induced fibrinogen binding to αIIb/β 3 , which was increased by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS. These results suggest that the inhibition of αIIb/β 3 activation is caused by the cAMP/A-kinase-dependent VASP (Ser 157 ) phosphorylation. In conclusion, these results demonstrate that inhibitory effects of cordycepin on platelet activation were due to inhibition of [Ca 2+ ] i mobilization through cAMP-dependent IP 3 RI (Ser 1756 ) phosphorylation and suppression of αIIb/β 3 activation through cAMP-dependent VASP (Ser 157 ) phosphorylation. These results strongly indicated that cordycepin might have therapeutic or preventive potential for platelet activation-mediated disorders including thrombosis, atherosclerosis, myocardial infarction, or cardiovascular disease.

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“…Investigations have reported that cordycepin has a variety of pharmacological effects including the stimulation of cAMP and cGMP production in platelets [28]. Polysaccharides are another active component of C. militaris.…”

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confidence: 99%

Enhancement of tyrosine hydroxylase expression by Cordyceps militaris

Sapkota

Kim²,

Park

et al. 2010

Open Life Sciences

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Abstract:Cordyceps militaris is a popular medicinal mushroom, and has received extensive attention for medical application because of its various physiological activities. However, there is limited information about the function of Cordyceps militaris on dopaminergic system. This study has attempted to evaluate the effect of cultured fruiting bodies of Cordyceps militaris extract (CME) on the expression of the tyrosine hydroxylase (TH) gene in PC12 cells and rat brain and stomach. Related mRNA levels were determined by the RT-PCR. Protein levels were measured by Western blot and immunohistochemistry. Our results demonstrated CME induced TH gene expression both in vitro and in vivo. Treatment of 10 μg/ml and 20 mg/kg CME to PC12 cells and rat cells yielded significant increases of TH protein levels. Significantly, TH immunoreactive neurons were detected not only in the brain but also in the stomach. TH-immunohistochemical staining was markedly enhanced in animals treated with CME compared to those in the untreated control. These results suggest that CME can upregulate the dopaminergic (DArgic) system, and may contribute to neuroprotection in neurodegenerative diseases.© Versita Sp. z o.o.

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Cordycepin (3′-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP- and cyclic GMP-dependent manner

Cited by 68 publications

References 40 publications

Cordycepin Attenuates Neointimal Formation by Inhibiting Reactive Oxygen Species–Mediated Responses in Vascular Smooth Muscle Cells in Rats

Cordycepin Attenuates Neointimal Formation by Inhibiting Reactive Oxygen Species–Mediated Responses in Vascular Smooth Muscle Cells in Rats

Inhibitory Effects of Cordycepin on Platelet ActivationviaRegulation of Cyclic Adenosine Monophosphate-downstream Pathway

Enhancement of tyrosine hydroxylase expression by Cordyceps militaris

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