curcumin and Coronary-Restenosis

Curcumin, the main ingredient of Curcuma longa L., has been used as a spice and as a herbal medicine with different therapeutic characteristics for centuries in Asian countries. This phytochemical has been shown to possess beneficial antiplatelet activity that has introduced it as a promising candidate for the treatment of thromboembolism, atherothrombosis, and inflammatory diseases. Platelet dysfunction under different circumstances may lead to cardiovascular disease, and curcumin has been shown to have beneficial effects on platelet dysfunction in several studies. Therefore, this narrative review is aimed to summarize available evidence on the antiplatelet activity of curcumin and related molecular mechanisms for this activity.

Topics: Animals; Blood Coagulation; Blood Platelets; Coronary Restenosis; Curcuma; Curcumin; Humans; Mice; Neovascularization, Physiologic; Platelet Activation; Platelet Aggregation Inhibitors; Rats; Thromboembolism; Thrombosis

Restenosis is one of the major complications affecting outcomes of percutaneous coronary interventions. The aims of this study were to formulate curcumin (CUR) nanoparticles by using only lipidic ingredients in the absence of any organic solvent and to determine key formulation parameters using 2-level factorial design. CUR nanoparticles were prepared using triglyceride and egg phosphatidylcholine (EPC) by high-pressure homogenization (HPH) and fully characterized regarding drug loading, particle size, zeta potential, stability, drug release profile, conductivity, viscosity, refractive index, stability, morphology and FTIR analysis. The efficacy of CUR nanoparticles in inhibiting restenosis was investigated in a rat carotid artery model. Balloon-injured rats were randomly assigned to two control (saline and empty carrier) groups and CUR nanoparticle treated group. Arterial restenosis was assessed by histomorphometric, immunohistochemical and CT angiography analyses. Optimized CUR nanoparticles with almost 70% drug entrapment, an average particle size of 58 nm, PDI < 0.2, spherical nanostructures and sustained release profile were prepared. In morphometric analysis, neointimal area and neointima/media ratio significantly decreased in the animal group received CUR nanoparticles compared with control groups. Expression of Ki67 was markedly lower in the CUR nanoformulation group. CT angiograms confirmed patency of the artery in this group. These results suggest that the new strategy of intramural delivery of CUR lipid-based nanoparticles can be considered as a novel approach to prevent neointimal hyperplasia.

Topics: Angioplasty; Animals; Carotid Arteries; Coronary Restenosis; Curcumin; Drug Carriers; Drug Liberation; Electric Conductivity; Green Chemistry Technology; Lipids; Male; Nanoparticles; Particle Size; Rats, Sprague-Dawley; Refractometry; Spectroscopy, Fourier Transform Infrared; Static Electricity; Tomography, X-Ray Computed; X-Ray Diffraction

Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, has been shown to play a vital role in vascular smooth muscle cell (SMC) proliferation and hence is a potential therapeutic target to inhibit vascular remodeling. The goal of this study was to evaluate the efficacy and mechanism of HO-3867 [((3E,5E)-3,5-bis[(4-fluorophenyl)methylidene]-1-[(1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl]piperidin-4-one)], a new synthetic curcuminoid, in the inhibition of vascular SMC proliferation and restenosis. Experiments were performed using human aortic SMCs and a rat carotid artery balloon injury model. HO-3867 (10 microM) significantly inhibited the proliferation of serum-stimulated SMCs by inducing cell cycle arrest at the G(1) phase (72% at 24 h) and apoptosis (at 48 h). HO-3867 significantly increased the phosphorylated and total levels of PTEN in SMCs. Suppression of PTEN expression by PTEN-small interfering RNA transfection reduced p53 and p21 levels and increased extracellular signal-regulated kinase 1/2 phosphorylation, resulting in decreased apoptosis. Conversely, overexpression of PTEN by cDNA transfection activated caspase-3 and increased apoptosis. Furthermore, HO-3867 significantly down-regulated matrix metalloproteinase (MMP)-2, MMP-9, and nuclear factor (NF)-kappaB expressions in SMCs. Finally, HO-3867 inhibited arterial neointimal hyperplasia through overexpression of PTEN and down-regulation of MMPs and NF-kappaB proteins. HO-3867 is a potent drug, capable of overexpressing PTEN, which is a key target in the prevention of vascular remodeling, including restenosis.

Topics: Activating Transcription Factor 2; Animals; Apoptosis; Benzylidene Compounds; Carotid Arteries; Caspase 3; Cell Cycle; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Curcumin; G1 Phase; Gene Expression; Growth Inhibitors; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Molecular Structure; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NF-kappa B; Piperidones; PTEN Phosphohydrolase; Rats; Rats, Sprague-Dawley; RNA, Small Interfering

In-stent restenosis is the major problem of percutaneous coronary interventions. Drug-eluting stent became a landmark in the treatment of coronary disease. Curcumin could be used for drug-eluting stent due to its antithrombogenity and antiproliferative properties. In this paper, 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were performed to decide the optimal concentration of curcumin for inhibiting the proliferation of vascular smooth muscle cells (VSMC). The result disclosed that more than 80% of VSMC were inhibited when the concentration of curcumin ranged from 2.5 microg/ml to 10 microg/ml (P < 0.05, compared to ethanol). Three weight percent curcumin-loaded films (3wt%, 5wt%, 8wt%) were prepared using a biodegradable polymer (poly (lactic acid-co-glycol acid), PLGA) as the carrier of curcumin. The release of lactate dehydrogenase (LDH) was used to evaluate the immediate toxicity of the curcumin-loaded PLGA films, and the three concentration curcumin-loaded films were revealed to be of no acute toxicity to the smooth muscle cells. The results of Alamar Blue test indicated that the curcumin-loaded films had better antiproliferation effect than did the 316 stainless steel (SS). Therefore, these films may be used for stent coating to inhibit the in-stent restenosis induced by VSMC proliferation.

Topics: Angioplasty, Balloon, Coronary; Animals; Carotid Arteries; Cell Proliferation; Cells, Cultured; Coated Materials, Biocompatible; Coronary Restenosis; Curcumin; Drug-Eluting Stents; Lactic Acid; Muscle, Smooth, Vascular; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats

In-stent restenosis is the major problem in clinical application of coronary stent. Drug-eluting stent became a landmark in the treatment of coronary disease. However, thrombosis is still a problem of drug-eluting stent. There has been clinical report indicating that thrombosis sometimes is induced by drug-eluting stent implantation in late stage. Curcumin could be used for drug-eluting stent due to its antithrombogenity and antiproliferative properties. In this paper, three weight percent curcumin-loaded films (3wt%, 5wt%, 8wt%) were prepared using a biodegradable polymer (poly (lactic acid-co-glycol acid), PLGA) as the carrier of curcumin. The component of curcumin-loaded film was analyzed by Fourier transform infrared spectroscopy (FTIR), and the major peaks of curcumin and PLGA were both observed in the composite film. The result of in vitro platelet adhesion test shows that the number of adhered platelet reduces, and few aggregated and activated platelets are observed. For all composite films, activated partial thromboplastin time (APTT) increases. The results indicate that the curcumin-loaded films have better anticoagulative effect when compared with PLGA. In addition, all anticoagulation tests indicate "the higher the drug content in the film, the better the anticoagulative effect".

Topics: Coated Materials, Biocompatible; Coronary Restenosis; Curcumin; Drug-Eluting Stents; Humans; Lactic Acid; Platelet Adhesiveness; Platelet Aggregation Inhibitors; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers

To investigate the effect and safety of Zedoary Turmeric Oil (ZTO)-eluting stents for post-coronary stenting restenosis prevention and treatment in the experimental dogs.. Bare stents, stents coated with polybutyl methacrylate/Nano silica, and stents eluted with 100 microg ZTO were randomly deployed in canine anterior descending or circumflex coronary artery. Four weeks after stent implantation, the dogs were sacrificed and the vascular histomorphologic changes in the stenting segment analyzed.. Thickened intima could be seen under light microscope in the bare or coated stents, but thinner in ZTO-duting stent, with no sub-intimal hemorrhage, medial or adventitial necrosis, wall adhesive thrombus, or infiltration of inflammatory cells. Scanning electric microscopy showed the intima was intact. Histomorphologic analysis showed that the thickness and area of neo-intima, and the lumen stenosis percent in artery stented with ZTO eluting stents were significantly lower than those stented with bare or coated stents (P <0.01), and thus the lumen cavity was expanded (P < 0.01), while no statistic significant difference between polymer and bare stents was found (P > 0.05).. ZTO-eluting stent is available and safe, and it could significantly inhibit the growth of neo-intimal in canine coronary mode after stenting, showing a restenosis preventive and treatment effect.

Topics: Animals; Coronary Restenosis; Curcuma; Disease Models, Animal; Dogs; Drug-Eluting Stents; Female; Humans; Male; Plant Extracts; Plant Oils; Random Allocation

A major complication of coronary stenting is in-stent restenosis (ISR) due to thrombus formation. We hypothesized that locally released curcumin from coronary stent surface would inhibit ISR due to thrombus formation because of antithrombosis of curcumin. In the present work, curcumin-eluting polylactic acid-co-glycolic acid (PLGA) films were fabricated and their properties in vitro were investigated. The in vitro platelet adhesion and activation, as well as protein adsorption on curcumin-loading PLGA films were investigated to evaluate the blood compatibility of curcumin-eluting films. The structure of curcumin-eluting PLGA film and control was examined by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy indicating that the peaks of curcumin did not shift in curcumin-eluting films. The results of contact angle and surface free energy indicated that loading curcumin in PLGA would make PLGA become more hydrophilic, which contributed to the increase of polar fraction of surface free energy. With the increase of curcumin in films, platelets adhering to the curcumin-eluting films decreased significantly. The number of activation platelets decreased after incorporating curcumin in PLGA films. Loading curcumin in PLGA film can markedly reduce the fibrinogen adsorption. All results indicated that incorporating curcumin in PLGA film can improve the blood compatibility of PLGA films. It can be used to fabricate drug-eluting stent to prevent thrombosis formation.

Topics: Adsorption; Biocompatible Materials; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Thrombosis; Curcumin; Lactic Acid; Materials Testing; Platelet Activation; Platelet Adhesiveness; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Proteins; Stents

This paper dealt with improving the blood compatibility of the rapamycin-eluting stent by incorporating curcumin. The rapamycin- and rapamycin/curcumin-loaded PLGA (poly(d,l-lactic acid-co-glycolic acid)) coatings were fabricated onto the surface of the stainless steel stents using an ultrasonic atomization spray method. The structure of the coating films was characterized by Fourier transform infrared spectroscopy (FTIR). The optical microscopy and scanning electron microscopy (SEM) images of the drug-eluting stents indicated that the surface of all drug-eluting stents was very smooth and uniform, and there were not webbings and "bridges" between struts. There were not any cracks and delaminations on stent surface after expanded by the angioplasty balloon. The in vitro platelet adhesion and activation were investigated by static platelet adhesion test and GMP140 (P-selection), respectively. The clotting time was examined by activated partially prothromplastin time (APTT) test. The fibrinogen adsorption on the drug-loaded PLGA films was evaluated by enzyme-linked immunosorbent assay (ELISA). All obtained data showed that incorporating curcumin in rapamycin-loaded PLGA coating can significantly decrease platelet adhesion and activation, prolong APTT clotting time as well as decrease the fibrinogen adsorption. All results indicated that incorporating curcumin in rapamycin-eluting coating obviously improve the blood compatibility of rapamycin-eluting stents. It was suggested that it may be possible to develop a drug-eluting stent which had the characteristics of not only good anti-proliferation but also improved anticoagulation.

Topics: Absorbable Implants; Adsorption; Angioplasty, Balloon, Coronary; Blood; Coated Materials, Biocompatible; Coronary Restenosis; Curcumin; Fibrinogen; Humans; In Vitro Techniques; Lactic Acid; Materials Testing; Microscopy, Electron, Scanning; Platelet Adhesiveness; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Sirolimus; Spectroscopy, Fourier Transform Infrared; Stents