Cilostazol as a Unique Antithrombotic Agent

Kambayashi, Jun-ichi; Liu, Yongge; Sun, Bing; Shakur, Yasmin; Yoshitake, Masuhiro; Czerwiec, Frank S.

doi:10.2174/1381612033453910

Cited by 166 publications

(161 citation statements)

References 0 publications

Supporting

Mentioning

158

Contrasting

Order By: Relevance

“…A PDE3 inhibitor, cilostazol, is used as a vasodilating anti-platelet drug for treating intermittent claudication, and in preclinical studies was shown to have a protective effect on endothelial cells by increasing eNOS activity 23) . Cilostazol increases intracellular cAMP content accordingly and activates protein kinase A (PKA) and PI3K/Akt signaling 24) .…”

Section: Cilostazol Inhibits Oxidative Stress-induced Premature Senesmentioning

confidence: 99%

SIRT1/eNOS Axis as a Potential Target against Vascular Senescence, Dysfunction and Atherosclerosis

Ota¹,

Eto²,

Ogawa³

et al. 2010

JAT

126

View full text Add to dashboard Cite

Sir2 (silent information regulator-2), an NAD -dependent histone deacetylase, is highly conserved in organisms ranging from archaea to humans. Yeast Sir2 is responsible for silencing at repeated DNA sequences in mating-type loci, telomeres and rDNA, and plays critical roles in DNA repair, stress resistance and longevity. The phenomenon of human aging is known to be a critical cardiovascular risk factor. Senescence of endothelial cells has been proposed to be involved in vascular dysfunction and atherogenesis. Recent studies have demonstrated that mammalian Sirt1 NAD -dependent protein deacetylase, the closest homologue of Sir2, regulates vascular angiogenesis, homeostasis and senescence. This review focuses on SIRT1 as a potential therapeutic target against atherosclerosis.J Atheroscler Thromb, 2010; 17:431-435.

show abstract

Section: Cilostazol Inhibits Oxidative Stress-induced Premature Senesmentioning

confidence: 99%

SIRT1/eNOS Axis as a Potential Target against Vascular Senescence, Dysfunction and Atherosclerosis

Ota¹,

Eto²,

Ogawa³

et al. 2010

JAT

126

View full text Add to dashboard Cite

show abstract

“…Therefore, CLZ has been used as a therapeutic agent for the improvement of symptoms in conditions such as cancer (2), pain accompanying chronic arterial obstruction (3), and for the amelioration (4) and, prevention of cerebral infarction (5). The agent is only administered orally because of its low water-solubility (6).…”

Section: Introductionmentioning

confidence: 99%

Enhanced percutaneous absorption of cilostazol nanocrystals using aqueous gel patch systems and clarification of the absorption mechanism

2018

View full text Add to dashboard Cite

Abstract. Cilostazol (CLZ), an anti-platelet agent, is primarily used following the onset of cerebral infarction. However, as CLZ is only marginally soluble in water, a strategy for patients with serious secondary conditions, such as impaired consciousness or aphagia, is required. In the present study, topical formulations containing CLZ nanocrystals (CLZ nano ) were designed to enhance percutaneous absorption. In addition, the mechanism of penetration of CLZ nano through rat skin was investigated. A topical formulation containing CLZ nanoparticles (CLZ nano gel patch) was prepared using a combination of recrystallization and ball milling of an aqueous gel. The particle size of CLZ nano was 74.5±6.2 nm (mean ± standard deviation). The concentration of permeated CLZ nano and penetration mechanism of the nanocrystals were measured in a percutaneous absorption experiment. The amount of penetrated CLZ, the penetration rate (J c ), the penetration coefficient through the skin (K p ) and the skin/preparation partition coefficient (K m ) for the CLZ nano gel patch were all significantly higher than those of the CLZ powder (CLZ micro ) gel patch, the CLZ nano ointment and the CLZ micro ointment. In in vitro percutaneous penetration experiments on the CLZ nano gel patches, there was a positive correlation between the number of CLZ nano . Following the application of the CLZ nano gel patch on rat skin, 98% of penetrated CLZ was observed in nanoparticle form; for the CLZ micro gel patch, this figure was 9%. In addition, the CLZ concentrations in the plasma of rats administered the CLZ nano gel patches were significantly higher than those of rats administered the CLZ nano CP gel and PEG ointments. It was suggested that CLZ nano (diameter <100 nm) were transferred through the intracellular spaces in the skin and then into peripheral blood vessels. To the best of our knowledge, this is the first report to elucidate the mechanism of the percutaneous penetration of nanocrystal medicines.

show abstract

“…Cilostazol increases intracellular cAMP concentrations by selectively blocking phosphodiesterase 3 (PDE-3), inhibiting platelet aggregation and inducing peripheral vasodilation [14]. Cilostazol is a potent antiplatelet drug used in clinical practice to treat patients with chronic vascular obstruction [15].…”

Section: Introductionmentioning

confidence: 99%

Cilostazol Inhibits Vascular Smooth Muscle Cell Proliferation and Reactive Oxygen Species Production through Activation of AMP-activated Protein Kinase Induced by Heme Oxygenase-1

Kim

Sung

Woo

et al. 2011

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cAMP levels and activates protein kinase A, thereby inhibiting vascular smooth muscle cell (VSMC) proliferation. W e investigated whether AMP-activated protein kinase (AMPK) activation induced by heme oxygenase-1 (HO-1) is a mediator of the beneficial effects of cilostazol and whether cilostazol may prevent cell proliferation and reactive oxygen species (ROS) production by activating AMPK in VSMC. In the present study, we investigated VSMC with various concentrations of cilostazol. Treatment with cilostazol increased HO-1 expression and phosphorylation of AMPK in a dose-and time-dependent manner. Cilostazol also significantly decreased platelet-derived growth factor (PDGF)-induced VSMC proliferation and ROS production by activating AMPK induced by HO-1. Pharmacological and genetic inhibition of HO-1 and AMPK blocked the cilostazol-induced inhibition of cell proliferation and ROS production.These data suggest that cilostazol-induced HO-1 expression and AMPK activation might attenuate PDGF-induced VSMC proliferation and ROS production.

show abstract

Cilostazol as a Unique Antithrombotic Agent

Cited by 166 publications

References 0 publications

SIRT1/eNOS Axis as a Potential Target against Vascular Senescence, Dysfunction and Atherosclerosis

SIRT1/eNOS Axis as a Potential Target against Vascular Senescence, Dysfunction and Atherosclerosis

Enhanced percutaneous absorption of cilostazol nanocrystals using aqueous gel patch systems and clarification of the absorption mechanism

Cilostazol Inhibits Vascular Smooth Muscle Cell Proliferation and Reactive Oxygen Species Production through Activation of AMP-activated Protein Kinase Induced by Heme Oxygenase-1

Contact Info

Product

Resources

About