OBJECTIVETo investigate the stability of curcumin, demethoxycurcumin and bisdemethoxycurcumin in different buffer solution.

METHODTo determine concentration of curcumin by HPLC when added curcumin, demethoxycurcumin and bisdemethoxycurcumin into the buffer solution the equation of degradation was established.

RESULTThe sequence of stability are bisdemethoxycurcumin > or = demethoxycurcumin > or =curcumin at the same condition.

CONCLUSIONThe demethoxycurcumin can stabilize curcumin more strong than the others. The demethoxycurcumin is a nature stabilizing agent for curcumin.

Chromatography, High Pressure Liquid ; Curcumin ; analogs & derivatives ; chemistry ; Drug Stability ; Hydrogen-Ion Concentration

OBJECTIVETo study and establish the fingerprint of Curcuma phaeocaulis by high performance liquid chromatography-mass spectrometry.

METHODLC-MS analysis was carried out in a Hewlett Packard model 1100 liquid chromatograph coupled with electrospray mass spectrometry. The analysis was performed on a ZORBAX RX-C18 column (4.6 mm x 250 mm, 5 microm) with a mobile phase of methanol-isopropanol-water (mathanoic acid 0.4%) in a gradient mode at a flow rate of 1.0 mL min(-1), and the column temperature of 35 degrees C. The wavelength of the UV detector was set at 254 nm. RSD values of precision, repeatability and stability of this LC-MS method were less than 5%. The total 10 batches of C. phaeocaulis from the different places of Sichuan province were detected, and different commodities and preparative methods were compared.

RESULTThe standard fingerprint of the extract of C. phaeocaulis, which collected in the different places of Sichuan province, was originated from the Similarity Evaluation System for Chromatographic Fingerprint of TCM 2004' software, and 15 common peaks existed in the fingerprint. Each peak in the fingerprint was separated well under the above analysis condition and similarities of the extracts of C. phaeocaulis samples of the ten batches were all above 0.90. By comparison of the retention time and the on-line UV spectra and their molecular weights of the chemical standards, peaks 4-6 and 9 were identified as curcumin (4), demethoxycurcumin (5), curcumenol (6), and curcumone (9), respectively.

CONCLUSIONThis LC-MS fingerprint and quantitative assessment can be used in the quality control of C. phaeocaulis.

Chromatography, Liquid ; methods ; Curcuma ; chemistry ; Curcumin ; analogs & derivatives ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods

OBJECTIVETo determine the role of a pharmacokinetic interaction in the protective effect of curcumin against the gastric damage induced by indomethacin administration as such or as its prodrug acemetacin.

METHODSWistar rats orally received single dose of indomethacin (30 mg/kg) with and without curcumin (30 mg/kg); gastric injury was evaluated by determining the total damaged area. Additional groups of rats received an oral single dose of indomethacin (30 mg/kg) or its prodrug acemetacin (34.86 mg/kg) in the presence or absence of curcumin (30 mg/kg). Indomethacin and acemetacin concentrations in plasma from blood draws were determined by high-performance liquid chromatography.Plasma concentration-against-time curves were constructed, and bioavailability parameters, maximal concentration (C) and area under the curve to the last sampling time (AUC) were estimated.

RESULTSConcomitant administration of indomethacin and curcumin resulted in a significantly reduced gastric damage compared to indomethacin alone. However, co-administration of curcumin did not produce any significant alteration in the bioavailability parameters of indomethacin and acemetacin after administration of either the active compound or the prodrug.

CONCLUSIONCurcumin exhibits a protective effect against indomethacin-induced gastric damage, but does not produce a reduction of the bioavailability of this nonsteroidal anti-inflammatory drug, indomethacin. Data thus suggest that a pharmacokinetic mechanism of action is not involved in curcumin gastroprotection.

Animals ; Biological Availability ; Curcumin ; pharmacology ; Drug Interactions ; Indomethacin ; analogs & derivatives ; pharmacokinetics ; toxicity ; Male ; Rats ; Rats, Wistar

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.
Chemistry, Pharmaceutical ; Curcumin ; chemistry ; Drug Stability ; Methylcellulose ; analogs & derivatives ; chemistry ; Polymers ; Solubility

The paper is aimed to study the dynamic accumulation regulation of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxyeurcumin (BDMC) in three strains of Curcuma longa, and provide scientific references for formalized cultivation, timely harvesting, quality control and breeding cultivation of C. longa. The accumulation regulation of the three curcumin derivatives was basically the same in rhizome of three strains. The relative contents decreased along with plant development growing, while the accumulation per hectare increased with plant development growing. The accumulation of curcuminoids per hectare could be taken as the assessment standard for the best harvest time of C. longa. A3 was the best strain in terms of Cur and BDMC content.
Curcuma ; chemistry ; growth & development ; metabolism ; Curcumin ; analogs & derivatives ; analysis ; metabolism ; Quality Control ; Rhizome ; chemistry ; growth & development ; metabolism

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

Curcumin has been reported to possess antitumor activity with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. In order to overcome these limitations and discover novel small molecules with potential antitumor activity, 29 curcumin mimics were synthesized, which were confirmed by 1H NMR and HR-MS, and their cytotoxic property was evaluated against five human cancer cell lines in vitro. Compounds 16, 18 and 19 exhibited good cytotoxic property, their IC50 value were even below 5 micromol x L(-1) to some cancer cell lines, 5-9 times better than curcumin.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Curcumin ; analogs & derivatives ; chemical synthesis ; pharmacology ; Drug Screening Assays, Antitumor ; Humans ; Inhibitory Concentration 50

OBJECTIVETo observe the effect of curcumin on nitric oxide (NO) in plasma of atherosclerotic rabbits, activity of constitutive nitric oxide synthase (cNOS) and asymmetric dimethylarginine (ADMA), and discuss curcumin's effect against AS and its correlation with ADMA.

METHODThirty-eight male Japanese white rabbits were randomly divided into four groups: the control group (eight rabbits fed with standard diets), the model group (ten rabbits fed with high-fat diets), the low dose curcumin group (ten rabbits fed with high-fat diets and 100 mg . kg-1 d -1 ) and the high dose curcumin group (ten rabbits fed with high-fat diets and 200 mg kg-1 d-1 curcumin). At the end of the 12th week, their plasmas were tested for TC, LDL-C, NO, endothelin (ET) , ADMA and activity of aortic cNOS. Aortic tissues were collected for histological examinations.

RESULTThe three groups fed with high-fat diets showed higher plasma ADMA and ET than the control group (P <0. 01) , but with decrease in plasma NO concentration and arterial cNOS activity (P <0. 01). Compared with the model group (P <0. 05) , the curcumin groups showed lower plasma ADMA and ET (P <0. 05), but higher plasma NO concentration and arterial cNOS activity than the model group (P <0. 01). There was no significant difference between the two curcumin groups.

CONCLUSIONCurcumin may play an important protective role in AS process by reducing plasma ADMA level. [Key words] atherosclerosis; asymmetric dimethylarginine; crucumin; nitric oxide; nitric oxide synthase

Animals ; Arginine ; analogs & derivatives ; blood ; Atherosclerosis ; blood ; drug therapy ; metabolism ; Curcumin ; therapeutic use ; Endothelium, Vascular ; drug effects ; Male ; Nitric Oxide Synthase ; metabolism ; Rabbits

OBJECTIVETo investigate the anti-proliferation of three different structural curcumin pigmen monomers on the bovine VSMC stimulated by ox-LDL and the effect on the expression of LDL-R.

METHODMTT and FCM were used to observe the anti-proliferation of three different on the bovine VSMC stimulated by ox-LDL and the effect on the expression of LDL-R.

RESULTox-LDL(2.5,5, 10 mg x L(-1)) had obvious proliferative effect on VSMC, P < 0.05, curcumin (16.5,33,66 micromol x L(-1)), demethoxycurcumin (33,66 micromol x L(-1)) and bisdemethoxycurcumin (66 micromol x L(-1)) had obvious inhibition effect on the proliferation of VSMC stimulated by 10 mg x L(-1) ox-LDL (P < 0.05, curcumin > demethoxycurcumin > bisdemethoxycurcumin) . Three curcumin (16.5,33,66 micromol x L(-1)) could obviously activate the expression of LDLR of VSMC.

CONCLUSIONThe three different structural curcumin pigmen monomers can not only inhibit the proliferation of bovine VSMC obviously stimulated by ox-LDL, but also promote the expression of LDL-R on bovine VSMC, that may be the mechanism of delaying the development of arteriosclerosis.

Animals ; Aorta ; cytology ; Cattle ; Cell Proliferation ; drug effects ; Cells, Cultured ; Curcuma ; chemistry ; Curcumin ; analogs & derivatives ; isolation & purification ; pharmacology ; Lipoproteins, LDL ; antagonists & inhibitors ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; metabolism ; Plants, Medicinal ; chemistry ; Receptors, LDL ; metabolism ; Structure-Activity Relationship

To study the in vitro anti-angiogenesis effect of three curcumin pigments (curcumin, demethoxycurcumin, bisdemethoxycurcumin). In the study, the inhibitory effect of the three curcumin pigments on proliferation of HUVEC cells induced by OX-LDL and the effect on migration of HUVEC cells were detected. The effect on neovascularization was observed by chorioallantoic membrane (CAM) test. The effect on cell adhesion factors ICAM-1 and VCAM-1 of HUVECs were tested by Real-time RT-PCR. It was found that the three curcumins could inhibit the proliferation of HUVEC cells induced by OX-LDL within the dosage range 4, 8, 16 mg x L(-1), with a dose-dependence. The proliferative effect of curcumins on HUVECs was greater than the other two derivatives (P < 0.01). All of the three curcumin pigments inhibited the migration of HUVEC cells and the angiogenesis of chick chorioallantoic membrane (CAM). The migration inhibition rate of curcumins at middle and high concentrations was greater than the other two (P < 0.01). All of the three curcumin could down-regulate the expression of VEGF and ICAM-1, and curcumins showed more obvious effect in down-regulating VEGF than demethoxycurcumin and bisdemethoxycurcumin(P < 0.01); Bisdemethoxycurcumin showed the most significant effect in down-regulating ICAM-1 (P < 0.01). All of the three showed no remarkable effect on expression of VCAM-1, and only bisdemethoxycurcumin showed the down-regulating effect (P < 0.05). According to the findings, all of the three curcumin pigments could resist angiogenesis by inhibiting proliferation and migration of endothelial cells and down-regulating the expression of VEGF and adhesion molecules ICAM-1.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Cell Movement ; drug effects ; Cells, Cultured ; Chorioallantoic Membrane ; drug effects ; Curcumin ; analogs & derivatives ; pharmacology ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; RNA, Messenger ; analysis ; Vascular Cell Adhesion Molecule-1 ; genetics ; Vascular Endothelial Growth Factor A ; genetics