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

To observe the influence of matrix metalloproteinases-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), CD47, L-selectin and advanced oxidation proteinproducts (AOPP) in osteoarthritis and the intervention of curcumin.A total of 20 male C57BL/6 mice (10.05-15.00 g) were randomly divided into control group, OA group, Cur25 group and Cur50 group (intraperitoneal injected 25 μmol/L or 50 μmol/L of curcumin everyday after modeling). After 4 weeks treatment, we observed the morphological changes of the gross specimen by immunohistochemical method, and observed the ultrastructure of cartilage tissue under electron microscope. The expression of MMP-2, MCP-1 and CD47 were detected by western blotting, and L-selectin and AOPP were detected by ELISA and spectrophotometer, respectively.In the cartilage tissue morphology, the chondrocytes of OA group showed obvious change, while Cur25 and Cur50 groups maintained the good cartilage cell membrane intact. Compared with control group, the expressions of MMP-2, MCP-1, L-selectin and AOPP in OA group, Cur25 group and Cur50 group were increased (all<0.05), while CD47 levels were decreased (all<0.05). Compared with OA group, the expressions of MMP-2, MCP-1, L-selectin and AOPP in Cur25 group and Cur50 group were decreased (all<0.05), while CD47 levels were increased (all<0.05), and such changes were more significant in Cur50 group (all<0.05).The MMP-2, MCP-1, CD47, L-selectin and AOPP are closely associated with the pathology course of OA. Curcumin has protection effect on cartilage, which can relieve joint cartilage degeneration, reduce cartilage inflammation and increase the metabolic activity of chondrocytes.
Advanced Oxidation Protein Products ; metabolism ; Animals ; Biomarkers ; CD47 Antigen ; metabolism ; Cartilage ; chemistry ; drug effects ; pathology ; Chemokine CCL2 ; metabolism ; Chondrocytes ; drug effects ; pathology ; Curcumin ; administration & dosage ; pharmacology ; Cytokines ; L-Selectin ; metabolism ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Mice, Inbred C57BL ; Osteoarthritis ; genetics ; pathology ; physiopathology ; Oxidative Stress

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

Recent research has demonstrated that advanced liver fibrosis in patients could be reversed, but no approved agents are available for the treatment and prevention of liver fibrosis in humans. Curcumin (CUR) is the principal curcuminoid of turmeric. Inhibitory effects of CUR and its underlying mechanisms in liver fibrogenesis have been explored. In the present study, we hypothesized that epigenetic mechanisms contribute to the protective effects of CUR against liver fibrosis. We used CCl4-induced liver injury in BALB/c mice and the rat hepatic stellate cell line HSC-T6 as experimental models. Genomic DNA methylation was analyzed by MeDIP-chip and verified by real-time PCR on MeDIP-enriched DNA. The mRNA and protein expressions of DNMT1, α-SMA, and Col1α1 were determined by real-time PCR and Western blotting, respectively. The methylation statuses of FGFR3, FZD10, Gpx4, and Hoxd3 were further confirmed by quantitative methylation-specific PCR (qMSP). Our results showed that CUR treatment reversed liver injury in vivo and in vitro, possibly through down regulation of DNMT1, α-SMA, and Col1α1 and by demethylation of the key genes. In conclusion, aberrant methylation is closely associated with liver fibrosis and CUR treatment may reverse liver fibrosis by epigenetic mechanisms.
Animals ; Cell Line ; Curcumin ; administration & dosage ; DNA Methylation ; drug effects ; Hepatic Stellate Cells ; drug effects ; metabolism ; Humans ; Liver ; drug effects ; metabolism ; Liver Cirrhosis ; drug therapy ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Protective Agents ; administration & dosage ; Proteins ; genetics ; metabolism ; Rats

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

Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid binding protein (A-FABP) level and whether this decrease benefits glucose control is unclear. One-hundred participants (n=50 administered curcuminoids, n=50 administered placebo) from our previous report on the effect of curcuminoids on type 2 diabetes in a 3-month intervention were assessed for levels of serum A-FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Curcuminoids supplementation also significantly increased serum superoxide dismutase (SOD) activity. The change in serum A-FABP levels showed positive correlations with changes in levels of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with curcuminoids. Further stepwise regression analysis showed that A-FABP was an independent predictor for levels of FFAs, SOD, and CRP. These results suggest that curcuminoids may exert anti-diabetic effects, at least in part, by reductions in serum A-FABP level. A-FABP reduction is associated with improved metabolic parameters in human type 2 diabetes.
Biomarkers ; blood ; Blood Glucose ; analysis ; Curcumin ; administration & dosage ; pharmacology ; therapeutic use ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; immunology ; Fatty Acid-Binding Proteins ; blood ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Obesity ; blood ; complications ; drug therapy ; immunology ; Oxidative Stress ; drug effects ; immunology ; Treatment Outcome

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 observe the changes in Aβ40, Aβ42 and ADDLs in brains of 3 month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin.

METHODAPPswe/PS1dE9dtg mice were randomly divided into the model group, the Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining (IHC) and the Western blot method were used to observe the changes in positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions.

RESULTBoth of the immunohistochemical staining and the Western blot method showed more positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group (P < 0.01). IHC showed a lower result in the Rosiglitazone group than the model group (P < 0.05), while Western blot showed a much lower result (P < 0.01). The number of Aβ40, Aβ42 and ADDLs positive cells and the protein expressions decreased in the curcumin high group, the medium group showed a significant decrease (P < 0.01), and the low dose group also showed reductions in the protein expressions of Aβ40 and Aβ42.

CONCLUSIONThe six-month intervention with curcumin can significantly reduce the expressions of hippocampal Aβ40, Aβ42 and ADDLs in brains of APPswe/PS1dE9 double transgenic mice. Whether curcumin can impact Aβ cascade reaction by down-regulating expressions of Aβ40, Aβ42 and ADDLs and show the neuroprotective effect needs further studies.

Alzheimer Disease ; drug therapy ; genetics ; metabolism ; Amyloid beta-Peptides ; genetics ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Curcumin ; administration & dosage ; Disease Models, Animal ; Hippocampus ; drug effects ; metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuroprotective Agents ; administration & dosage ; Plant Extracts ; 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