Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes, on the basis of single factor tests, orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading, yield, particle size distribution, electron microscope analysis (SEM) , infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 45 degrees C, crystallization pressure 10 MPa, curcumin concentration 8 g x L(-1), solvent flow rate 0.9 mL x min(-1), and CO2 velocity 4 L x min(-1). Under the optimal conditions, the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%, and the average particle size of the particles was 20.632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.
Carbon Dioxide ; chemistry ; Cellulose ; administration & dosage ; analogs & derivatives ; chemistry ; Curcumin ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Solubility ; Solvents ; Technology, Pharmaceutical

MicroRNAs (miRNAs) are a set of non-coding small RNA molecules that play a critical role in regulation of protein coding genes in cells. MiRNAs have been extensively studied as novel biomarkers, therapeutic targets, and new drugs in various human diseases. Breast cancer is a one of the leading tumor types significantly affecting women health worldwide. Over the past decade, a number of natural agents, such as paclitaxel and curcumin, have been applied for treatment and prevention of breast cancer due to their relatively low toxicity. However, the mechanisms of action have not been completely understood. Investigation on miRNAs is able to potentially provide a novel insight into better understanding the anticancer activities of these natural products. Given that a single miRNA can target multiple genes, theoretically, those genes involved in a certain phenotype can be clustered with one or a few miRNAs. Therefore, pleiotropic activities of natural agents should be interpreted by interactions between selected miRNAs and their targets. In this review, we summarize the latest publications related to the alterations of miRNAs by two natural agents (paclitaxel and curcumin) that are currently used in intervention of breast cancer, and conclude that the mechanism involving the regulation of miRNA expression is one of the keys to understand pleiotropic activities of natural agents.
Animals ; Antineoplastic Agents ; administration & dosage ; Biological Products ; administration & dosage ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; prevention & control ; Curcumin ; administration & dosage ; Female ; Humans ; MicroRNAs ; genetics ; metabolism ; Paclitaxel ; administration & dosage

To synthetize 3-carboxypropyl-triphenylphosponium bromide-polycaprolacton-CTPP-PEG-PC, and prepare curcumin CTPP-PEG-PCL micelles by using the self-assembled emulsion solvent evaporation method, in order to determine the critical micelle concentration (CMC) with the pyrene fluorescent probe technology, detect the particle size, entrapment efficiency (%), morpheme and in vitro release rate, and evaluate the cytotoxicity of hepatic stellate cells with MTT assay. The structure of CTPP-PEG-PCL had been identified by 1H-NMR spectra. Specifically, the CMC of polymer was 2.25 mg x L(-1), the average size was 190 nm, the drug content was (0.66 +/- 0.008) g x L(-1), and the entrapment efficiency was (94 +/- 0.6)%. The in vitro release results showed curcumin micelles had a significant higher inhibition ratio in the growth of hepatic stellate cells than crude curcumin (P < 0.05). This suggested that CTPP-PEG-PCL micelles feature low CMC, high encapsulation efficiency and notable inhibition effect in growth of hepatic stellate cells.
Cell Line ; Cell Proliferation ; drug effects ; Curcumin ; administration & dosage ; chemistry ; pharmacology ; Hepatic Stellate Cells ; drug effects ; Micelles ; Polyesters ; administration & dosage ; chemistry ; Polyethylene Glycols ; administration & dosage ; chemistry

Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.
Acetylcysteine ; pharmacology ; Administration, Intranasal ; Animals ; Biological Availability ; Brain ; Brain Chemistry ; Chromatography, Liquid ; Curcumin ; pharmacokinetics ; Rats ; Tandem Mass Spectrometry ; Tissue Distribution

The paper aimed to find the optimal combination and evaluation of the interactions of antitumor effect of the curcumin (Cur) and adriamycin (ADM) in vitro. According to the factorial design and data characteristics, the parameter method combined with the response surface approach were used to analyze the pharmacodynamic interactions of in vitro antitumor effects of the combination of Cur and ADM at different dosages. The results showed that the dose-effect relationship of the combination with the ratio of ADM-Cur 1:3 showed significant differences in comparison with either used alone. The dose-effect curve was shift left in combination. The combination of adriamycin (ADM, 0.693-2.132 micromol L(-1)) and curcumin (Cur, 2.047-6.304 micromol L(-1)) with a fixed ratio (1:3) showed a synergism. With increasing doses of the combination, there is an additive effect. Computer simulation showed a trend of decreasing difference between the observed and expected effects with the dose increasing in Cur from 6.304 to 16.0 micromol L(-1) and ADM from 2.132 to 5.3 micromol L(-1). The response surface analysis showed the optimal combination to be Cur 18.50 micromol L(-1) and ADM 3.89 micromol L(-1) with a ratio of 5:1. This study suggests that the parameter method combined with the response surface analysis provides richer and more reasonable information, and is helpful for quantitative design of drug combination therapy and to describe the nature and degree of drug interaction.
Algorithms ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Proliferation ; drug effects ; Computer Simulation ; Curcumin ; administration & dosage ; isolation & purification ; pharmacology ; Dose-Response Relationship, Drug ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Synergism ; Humans ; K562 Cells

OBJECTIVETo research the pharmacological action of curcumin solid dispersions (SDs, curcumin and polyvinylpyrrolidone (PVP) k30 in the ratio of 1:8) was investigated on experimental gastric ulcer in rats and mice.

METHODAnimals were randomly divided into several experimental groups. Each group consisted of 10 animals. The control group received PVP vehicle (720 mg x kg(-1), po) throughout the course of the experiments. The treatment groups received different doses of curcumin SDs (equivalent to curcumin 10, 30 and 90 mg x kg(-1), po), and ranitidine (27 mg x kg(-1), po) was used as the positive control. In acetic acid-induced gastric ulcers model, serum NO, plasma ET and gastric ulcer indexes of rats were measured after oral administration for 14 d. In rat ulcer model induced by pylorus-ligature, gastric volume pepsin and gastric ulcer indexes of rats were measured after oral administration for 3 d and pylorus-ligature inducement for 16 h. Gastric ulcer indexes of mice were measurement after oral administration for 3 d and subcutaneous injection reserpine 10 mg x kg(-1).

RESULTThe results showed that curcumin SDs (equivalent to curcumin 30, and 90 mg x kg(-1), po) could reduce the ulcer indexes 4.59 +/- 0.96 and 3.33 +/- 0.93 (P < 0.01), and increase serum NO level (29.75 +/- 5.90) mmol x L(-1) (P < 0.05) and (39.63 +/- 12.73) mmol x L(-1) (P < 0.01), compared to gastric index 5.87 +/- 0.48 and NO level (23.63 +/- 5.73) mmol x L(-1) in control group. Compared to plasma ET (163.65 +/- 63.84) ng x L(-1) in control group, curcumin SDs (equivalent to 90 mg x kg(-1), po) could decrease plasma ET level (104.22 +/- 63.84) ng x L(-1) (P < 0.05). Compared to gastric ulcer indexes 4.25 +/- 0.71 of control group in rat pylorus-ligature model, curcumin SDs (equivalent to curcumin 90 mg x kg(-1)) could reduce gastric ulcer to 2.38 +/- 0.74 (P < 0.01). Compared to gastric volume (14.61 +/- 1.80) mL, acidity of gastric juice (87.70 +/- 9.84) mmol x L(-1), and the activity of pepsin (408.63 +/- 41.75) U x mL(-1), curcumin SDs (equivalent to curcumin 30, 90 mg x kg(-1)) could reduce gastric volume to (12.68 +/- 1.46) mL (P < 0.05) and (9.99 +/- 0.79) mL (P < 0.01), reduce acidity of gastric juice to (77.62 +/- 8.34) mmol x L(-1) (P < 0.05) and (65.77 +/- 8.19) mmol x L(-1) (P < 0.01), inhibit the activity of pepsin to (358.13 +/- 37.44) U x mL(-1) (P < 0.05) and (292.13 +/- 41.93) U x mL(-1) (P < 0.01). In reserpine-induce gastric ulcer model, curcumin SDs (equivalent to curcumin 30, 90 mg x kg(-1)) could reduce gastric ulcer indexes to 3.88 +/- 0.40 and 3.03 +/- 0.64 (P < 0.01), compared to that of control group 5.13 +/- 0.59.

CONCLUSIONSeveral animal gastric ulcer models prove that curcumin SDs has anti-gastric ulcer effects by inhibiting gastric acid secretion, reducing gastric juice acidity, inhibiting the activity of pepsin and promoting healing of ulcer. These findings show a potential application of curcumin SDs as an anti-ulcerogenic drug.

Animals ; Anti-Ulcer Agents ; administration & dosage ; chemistry ; Curcumin ; administration & dosage ; chemistry ; Disease Models, Animal ; Female ; Humans ; Male ; Plant Extracts ; administration & dosage ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; drug therapy

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.
Administration, Oral ; Anaphylaxis* ; Animals ; Arachidonate 5-Lipoxygenase ; Curcuma ; Curcumin* ; Cyclooxygenase 2 ; Histamine* ; Immunoglobulin E ; Immunoglobulins* ; Leukotriene C4 ; Mast Cells* ; Mice* ; Mitogen-Activated Protein Kinases ; Phospholipases ; Phosphorylation ; Prostaglandin D2

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.
Administration, Oral ; Anaphylaxis* ; Animals ; Arachidonate 5-Lipoxygenase ; Curcuma ; Curcumin* ; Cyclooxygenase 2 ; Histamine* ; Immunoglobulin E ; Immunoglobulins* ; Leukotriene C4 ; Mast Cells* ; Mice* ; Mitogen-Activated Protein Kinases ; Phospholipases ; Phosphorylation ; Prostaglandin D2

OBJECTIVETo explore the effect of curcumin (CMN) on contrast-induced nephropathy (CIN) in rats and explore the potential mechanisms focusing on heme oxygenase-1 (HO-1) expression.

METHODSMale SD rats (n = 24) were randomly divided into four groups (n = 6 each): control group (group A), diatrizoate group (DTZ, group B), DTZ + CMN group (group C), DTZ + CMN + zinc protoporphyrin IX group (group D). All rats were fed with normal chow for 1 week, right kidney was excised under anesthesia and rats were fed with normal chow for another 4 weeks. Afterwards, rats in group A was fed with normal chow, and rats in group B to D were fed with low-salt diet. All rats were injected furosemide 2 mg×kg(-1)×d(-1) for 7 days intramuscularly. At the beginning of the 7(th) day, rats in group C were injected intramuscularly with CMN 20 mg/kg, rats in group D were injected with CMN (20 mg/kg) + zinc protoporphyrin IX (7.5 mg/kg) while rats in group A and B were injected with equal volume of physiological saline. At the end of the 7(th) day, indometacin (10 mg/kg) was injected into tail vein of all rats. One hour later, 60% DTZ (8 ml/kg) was injected to rats in the group B, C and D while equal volume saline was injected to rats in group A through common carotid artery. After 48 hours, blood was drawn from the hearts of deeply anesthetized rats and kidney tissue was obtained for histology, HO-1, Bax, Bcl-2 expression and the apoptotic index measurements.

RESULTSThe serum creatinine of group B, C and D [(83.67 ± 4.50) µmol/L, (63.67 ± 4.76) µmol/L, (104.17 ± 4.58) µmol/L] was significantly higher than that of group A [(41.50 ± 5.58) µmol/L, all P < 0.05], the serum creatinine was significantly higher in group B than in group C and lower than in group D (all P < 0.05). HO-1 expression of group B, C and D was significantly higher than that of group A (all P < 0.05), significantly higher in group C than in group B and D (all P < 0.05). HO-1 activity of group A, B and C was significantly higher than that of group D(all P < 0.05), HO-1 activity was significantly higher in group B than in group A and significantly lower in group B than in group C (all P < 0.05). Bax, Bcl-2 expression and apoptosis index of group B, C and D were significantly higher than that of group A (all P < 0.05), while Bcl-2/Bax of group B, C and D were significantly lower than that of group A (all P < 0.05). Bcl-2 and Bcl-2/Bax were significantly higher while apoptosis index was significantly lower in group C than in group B (all P < 0.05). Bax and apoptosis index were significantly higher and Bcl-2, Bcl-2/Bax were significantly lower in group D than in group B (all P < 0.05).

CONCLUSIONCMN could protect against contrast-induced nephropathy through reducing renal cell apoptosis via upregulating HO-1 expression and activating HO-1 activity in rats.

Animals ; Contrast Media ; administration & dosage ; Curcumin ; pharmacology ; Disease Models, Animal ; Heme Oxygenase (Decyclizing) ; metabolism ; Kidney ; metabolism ; Kidney Diseases ; chemically induced ; prevention & control ; Male ; Rats ; Rats, Sprague-Dawley

The aim of this study is to investigate the feasibility of silica-coated ethosome as a novel oral delivery system for the poorly water-soluble curcumin (as a model drug). The silica-coated ethosomes loading curcumin (CU-SE) were prepared by alcohol injection method with homogenization, followed by the precipitation of silica by sol-gel process. The physical and chemical features of CU-SEs, and curcumin release were determined in vitro. The pharmacodynamics and bioavailability measurements were sequentially performed. The mean diameter of CU-SE was (478.5 +/- 80.3) nm and the polydispersity index was 0.285 +/- 0.042, while the mean value of apparent drug entrapment efficiency was 80.77%. In vitro assays demonstrated that CU-SEs were significantly stable with improved release properties when compared with curcumin-loaded ethosomes (CU-ETs) without silica-coatings. The bioavailability of CU-SEs and CU-ETs was 11.86- and 5.25-fold higher, respectively, than that of curcumin suspensions (CU-SUs) in in vivo assays. The silica coatings significantly promoted the stability of ethosomes and CU-SEs exhibited 2.26-fold increase in bioavailablity relative to CU-ETs, indicating that the silica-coated ethosomes might be a potential approach for oral delivery of poorly water-soluble drugs especially the active ingredients of traditional Chinese medicine with improved bioavailability.
Administration, Oral ; Animals ; Biological Availability ; Coated Materials, Biocompatible ; chemistry ; Curcumin ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Carriers ; Ethanol ; chemistry ; Liposomes ; chemistry ; Male ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; chemistry ; Solubility