Bisdemethoxycurcumin Research Articles

Degradation of curcuminoids by in vitro pure culture fermentation.

Colonic bacteria may mediate the transformation of curcuminoids, but studies of this metabolism are limited. Here, the metabolism of curcuminoids by Escherichia fergusonii (ATCC 35469) and two Escherichia coli strains (ATCC 8739 and DH10B) was examined in modified medium for colon bacteria (mMCB) with or without pig cecal fluid. LC-MS analysis showed that 16-37% of curcumin, 6-16% of demethoxycurcumin (DMC) and 7-15% of bis-demethoxycurcumin (Bis-DMC), and 7-15% of bis-demethoxycurcumin (Bis-DMC) were converted following 36 h of fermentation, with the amount of curcuminoids degraded varying depending on the bacterial strain and medium used. Three metabolites (dihydrocurcumin (DHC), tetrahydrocurcumin (THC), and ferulic acid (FA)) were found in fermentation cultures with all strains used. In addition, a compound with m/z [M - H](-) 470 was found and identified to be a curcumin adduct (curcumin-l-cysteine), using accurate mass FT-ICR-MS. This study provides insights into the bacterial metabolism of curcuminoids.

Rapid and Efficient Extraction of Curcumins from Curry Powder Using Supercritical CO2

E-mail: pyod@kangwon.ac.krReceived March 20, 2014, Accepted June 16, 2014Key Words : Supercritical fluid extraction, Curry, Curcumin, Carbon dioxideA dried curry powder is well known food additive in manyAsian countries. Curcumins are main coloring substancesand active compounds in curry powder which is the naturalyellow pigment in turmeric isolated from the rhizome of theplant Curcuma longa. Curcumins are consisted of curcumin([(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and two related compounds, demethoxy-curcumin (DMC) and bis demethoxycurcumin (BDMC).The chemical structure of curcumin is shown in Figure 1.Curcumins gives specific flavor and yellow color to currypowder.

Ultrasonic-Assisted Extraction of Curcumin Complexed with Methyl-β-Cyclodextrin

Turmeric flavour is important in Asian cuisine; however, the production of turmeric-based ingredient with the current method of extraction of turmeric oleoresin is very laborious, time consuming and consumes large amount of solvent, coupled with limited solubility in aqueous solution, which limits its application to food system. The extract was optimised by determining the content of three marker curcuminoid compounds, namely, curcumin (C), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). The optimised extraction parameters for ultrasonic-assisted extraction (UAE) with aqueous extraction solvent for curcuminoids were amplitude of 100, particle size of 0.30–0.60 mm, extraction time of 20 min, extraction solvent volume of 10 mL and extraction temperature of 60 °C. The applications showed remarkable improvements in terms of reduced extraction time, solvent consumption, extraction yield and the quality of extracts. The turmeric oleoresin was successfully solubilised in aqueous solution by forming inclusion complex with methyl-β-cyclodextrin (Mβ-CD). Phase solubility studies used curcumin as a marker compounds to represent turmeric oleoresin. In the presence of Mβ-CD, the curcumin was enhanced. Result from characterisation of inclusion complexes with Fourier transform infrared (FTIR) spectrometry indicates that all the mixing methods were found to be suitable for encapsulation. However, scanning electron microscopy (SEM) shows a drastic change in particle sizes, indicating a formation of a new solid phase in kneading method, implying it as the best mixing method.

RETRACTED ARTICLE: PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids: UPLC/ESI-Q-ToF-MS/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model

Stroke is a one of the leading causes of disease and deaths worldwide, which causes irreversible deterioration of the central nervous system. Curcuminoids are reported to have a potential role in the amelioration of cerebral ischemia but they exhibit low serum and tissue levels due to low solubility and poor absorption. Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)-loaded PNIPAM nanoparticles (NPs) were prepared by free radical polymerization and characterized for particles size, entrapment efficiency, zeta potential, in vitro release and ex vivo permeation study. Optimized CUR, DMC and BDMC-loaded NPs had the mean size of 92.46 ± 2.8, 91.23 ± 4.2 and 94.28 ± 1.91 nm; zeta potential of −16.2 ± 1.42, −15.6 ± 1.33 and −16.6 ± 1.21 mV; loading capacity of 39.31 ± 3.7, 38.91 ± 3.6 and 40.61 ± 3.6% and entrapment efficiency of 84.63 ± 4.2, 84.71 ± 3.99 and 85.73 ± 4.31%, respectively. Ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectroscopy based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency and brain drug-targeting potential studies post-intranasal (i.n.) administration which showed enhanced bioavailability of curcuminoids in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) and reduced cytokines levels (TNF-α and IL-1β) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of curcuminoids NPs. Finally, the toxicity study was performed which revealed safe nature of developed NPs.

Chitosan–starch nanocomposite particles as a drug carrier for the delivery of bis-desmethoxy curcumin analog

The conventional drug delivery system has serious limitations such as lack of target specificity, altered effects and diminished potency. These limitations can be overcome by using biocompatible polymer as an effective drug delivery system. In this study, bis-demethoxy curcumin analog loaded Chitosan–starch (BDMCA–CS) nanocomposite particles were developed using different ratios of Chitosan and starch (3:1, 1:1 & 1:3) by ionic gelation method. The entrapment efficiency and drug loading capacity were found to be high for the formulation with the ratio 3:1 of BDMCA:CS. Physical characterization of the nanocomposite particles was determined using DLS and FTIR. The morphology of the BDMCA–CS nanocomposite particles were found to be spherical and regular by SEM analysis. In-vitro drug release profile of the BDMCA–CS nanocomposite particles showed a very slow and sustained diffusion controlled release of the drug. The cancer cells targeting ability of the BDMCA–CS nanocomposite particles were confirmed by performing MTT assay on MCF-7 breast cancer cell lines and VERO cell lines.

Molecularly imprinted polymers for cleanup and selective extraction of curcuminoids in medicinal herbal extracts.

This paper describes the synthesis of novel molecularly imprinted polymers (MIPs), prepared by a noncovalent imprinting approach, for cleanup and preconcentration of curcumin (CUR) and bisdemethoxycurcumin (BDMC) from medicinal herbal extracts and further analysis by high-performance liquid chromatography with fluorescence detection (HPLC-FLD). Two molecular mimics, a mixture of reduced BDMCs and 4-(4-hydroxyphenyl)-2-butanone (HPB), have been synthesized and applied as templates for MIP synthesis. The polymers were prepared using N-(2-aminoethyl) methacrylamide (EAMA) as functional monomer, ethylene glycol dimethacrylate (EDMA) as the cross-linker (in a 1:5 molar ratio), and a mixture of acetonitrile/dimethylsulfoxide (90%, v/v) as porogen. MIPs prepared using a mixture of reduced BDMCs as template showed higher selectivity for CUR and BDMC than those obtained with HPB, with imprinting factors of 3.5 and 2.7 for CUR and BDMC, respectively, using H2O/acetonitrile (65:35, v/v) as mobile phase. The adsorption isotherms for CUR in the MIP and the nonimprinted polymer (NIP) were fitted to the Freundlich isotherm model, and the calculated average binding affinities for CUR were (17 ± 2) and (8 ± 1) mM(-1) for the MIP and the NIP, respectively. The polymers were packed into solid-phase extraction (SPE) cartridges, and the optimized molecularly imprinted solid-phase extraction (MISPE-HPLC) with fluorescence detection (FLD) method allowed the extraction of both curcuminoids from aqueous samples (50 mM NH4Ac, pH 8.8) followed by a selective washing with acetonitrile/NH4Ac, 50 mM at pH 8.8 (30:70%, v/v), and elution with 3 × 1 mL of MeOH. Good recoveries and precision ranging between 87 and 92%, with relative standard deviation (RSD) of <5.3% (n = 3), were obtained after the preconcentration of 10-mL solutions containing both CUR and BDMC at concentrations in the range of 0-500 μg L(-1). The optimized method has been applied to the analysis of both curcuminoids in medicinal herbal extracts.

Bis-demethoxy curcumin analog nanoparticles: synthesis, characterization, and anticancer activity in vitro.

We have optimized a protocol for the preparation of bisdemethoxy curcumin analog nanoparticles (BDMCA-NP) by the solvent assisted process. The structural similarities between bulk and nano BDMCA were determined by Co-TLC, NMR and F-TIR. This shows that our synthesis protocol enhanced the dispersibility and reduce the size of BDMCA without altering the integrity of functional moieties and structure, which is crucial for anticancer and antioxidant activities. The morphology and size of BDMCA-NP as determined by SEM, HRTEM and DLS was found to be around 80 nm. BDMCA-NP treated breast cancer cell lines (MCF 7) showed cell death as characterized by MTT assay. Flow cytometric analysis of BDMCA-NP treated MCF 7 cell lines showed an increase of cell count in G2/M phase indicates the cell cycle arrest. Western blot analysis revealed the presence of caspase 3, caspase 9, cleaved fragments of PARP and Bax proteins in the BDMCA-NP treated MCF 7 cell lines, but not in untreated cell lines. To recap, we have prepared BDMCA-NP by solvent assisted process, which exerted anticancer activity against breast cancer cells, which may be due to (i) enhanced dispersibility and surface: volume ratio, (ii) apoptosis (iii) mitochondrial pathway induced cell death, (iv) G2/M phase cell cycle arrest and (v) disassembly of mitotic spindle of the cancer cells. Thus, nano BDMCA can be used as a potent anticancer agent.

Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models

BackgroundAlzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models.MethodsNeuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated.ResultsBDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC50, which was 20 and 13 times lower than those of CCN and DMCCN respectively. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1.ConclusionFurther studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers.

A high-throughput quantification method of curcuminoids and curcumin metabolites in human plasma via high-performance liquid chromatography/tandem mass spectrometry

Curcuminoids, a mixture of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), have shown a variety of clinical benefits for several human chronic diseases including osteoarthritis, rheumatoarthritis, and type II diabetes. However, the oral bioavailability of curcumin is extremely low due to its avid metabolism to curcumin O-glucuronide (COG), curcumin O-sulfate (COS), tetrahydrocurcumin (THC), and other minor metabolites. This paper reports a unique liquid chromatography/tandem mass spectrometry (LC-MS/MS) method to quantify curcumin, DMC, BDMC, COG, COS, and THC simultaneously in human plasma. These compounds were extracted with ethyl acetate from human plasma, separated on a BetaBasic-8 column, and monitored on a triple quadruple mass spectrometer coupled with API electrospray under a negative ion mode. The linearity of these respective curcuminoids and curcumin metabolites was shown in the range of 2-1000ng/mL with 85-115% accuracy and ≤20% precision in human plasma. This method was validated according to the US FDA GLP analytic criteria and applied to characterize the pharmacokinetics of curcumin, COG, and COS in human plasma after an oral dose of bioavailable curcumin (nanoemulsion curcumin).

The Effects of Blanching, Harvest Time and Location (with a Minor Look at Postharvest Blighting) on Oleoresin Yields, Percent Curcuminoids and Levels of Antioxidant Activity of Turmeric (Curcuma longa) Rhizomes Grown in Jamaica

Turmeric (Curcuma longa) grown in Jamaica was studied for its naturally occurring linear diarylheptanoid compounds namely curcumin, Bis-Demethoxy Curcumin (BDMC), Demethoxy Curucmin(DMC) and for its antioxidant activity. Evaluations were conducted on the basis of whether or not there were any potential effects of blanching, harvest time and location of growth on the quantity and quality of turmeric oleoresins. The highest antioxidant activity of 92.86% was obtained from turmeric rhizomes grown in the parish of Hanover while the highest turmeric oleoresin yields of 14.87% were obtained from the 15 minute blanched-treated turmeric rhizomes. With a new analog-selective RP-HPLC method, the curcumin, DMC, and BDMC were qualified and quantified. It was found that the highest yield of curcumin content of 22.69% was obtained from the 15 minute ‘blanched’ samples grown in the parish of Hanover from the first harvest period for the study. An analytical method validation with linear equations and correlation of regressions of R2=0.9991, R2=0.999.3, R2=0.9998 and R2=0.9992 for inter-day precision analyses were performed to validate the HPLC method.

Quick supramolecular solvent-based microextraction for quantification of low curcuminoid content in food

There is a need to monitor the consumption of curcuminoids, an EU-permitted natural colour in food, to ensure that acceptable daily intakes are not exceeded, especially by young children. This paper describes a sensitive method able to quantify low contents of curcumin (CUR), demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC) in foodstuffs. The method was based on a single-step extraction by use of a supramolecular solvent (SUPRAS) made up of reverse aggregates of decanoic acid, and direct analysis of the extract by use of liquid chromatography-photodiode array (PDA) detection. The extraction involved the stirring of 200 mg foodstuff with 600 μL SUPRAS for 15 min. No cleanup or concentration of the extracts was required. Curcuminoid solubilisation occurred via dispersion and hydrogen bonding. The method was used for the determination of curcuminoids in different types of foodstuff (snack, gelatine, yoghurt, mayonnaise, butter, candy and fish products) that encompassed a wide range of protein, fat, carbohydrate, sugar and water contents (0.85-11.04, 0-81.11, 0.06-75, 0.06-79.48, and 10.08-85.10 g, respectively, in each 100 g of food). Method quantification limits for the foodstuffs analysed were in the ranges 2.9-7.7, 2.8-11.2 and 3.3-9.0 μg kg(-1) for CUR, DMC and BDMC, respectively. The concentrations of curcuminoids detected in the foodstuffs and the recoveries obtained from fortified samples were in the ranges ND-284, ND-201 and ND-61.3 μg kg(-1), and 82-106, 89-106 and 90-102 %, for CUR, DMC and BDMC, respectively. The relative standard deviations were in the range 2-7 %. This method enabled quick and simple microextraction of curcuminoids with minimal solvent consumption, while delivering accurate and precise data.

On-line Screening HPLC-ABTS를 이용한 강황으로부터 Curcuminoids의 생물활성 분석

강황(Curcuma longa)으로부터 bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) 및 curcumin의 생물 활성을 offline-ABTS 측정법과 on-line screening high-performance liquid chromatography (HPLC)-ABTS 측정법을 적용한 빠른 스크리닝을 통해 정량 및 성분 분리를 하였다. 이때, off-line-ABTS와 on-line screening HPLC-ABTS 비교는 미미한 오차를 보여주었다. Free radical scavengers in the bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) and curcumin of turmeric (Curcuma longa) were screened, identified, quantified and isolation using coupled off-line-2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and on-line screening high-performance liquid chromatography (HPLC)-ABTS assay. There was a very small margin of error between the off-line-ABTS method and the on-line screening HPLC-ABTS method.

Rapid separation and quantitation of curcuminoids combining pseudo two-dimensional liquid flash chromatography and NMR spectroscopy.

Rapid separation, characterization and quantitation of curcuminoids are important owing to their numerous pharmacological properties including antimicrobial, antiviral, antifungal, anticancer, and anti-inflammatory activities. In the present study, pseudo two-dimensional liquid flash chromatography was used for the separation of four curcuminoids (curcumin, demethoxy curcumin, bisdemethoxy curcumin and dihydro bisdemethoxy curcumin) for the first time. Silica and diol columns were used for separation of curcuminoids using gradient mobile phase. The separated peaks were monitored at 244, 360nm to obtain four compounds. The purity of compounds were determined by rapid quantitative (1)H NMR (qNMR) using 3-(trimethylsilyl) propionic-(2,2,3,3-d4) acid sodium salt (TSP-d4) (0.012%) in D2O. These results were compared with those obtained by HPLC method. The purity of isolated curcuminoids using pseudo 2D chromatography was found to be in the range of 92.4-95.45%. The structures of these compounds were characterized unambiguously using (13)C (APT) NMR spectra. The developed pseudo 2D separation technique has the advantage of simplified automation with shorter run time compared to conventional separation techniques. The method that combines rapid pseudo 2D separation and simple quantitation using qNMR reported herein can be of wide utility for routine analysis of curcuminoids in complex mixtures.

The Quantitative Analysis of Curcuminoids in a Food Additive and Foods Evaluated Using Rapid HPLC with Electrochemical, UV or Fluorescence Detection

Turmeric, the rhizomatous herbaceous perennial plant of the ginger family, in dried powdered form is used as a culinary additive to impart a distinctive yellow-orange color to Pakistani, Indian and Thai cuisines. Although turmeric has been used for many years in Ayurvedic medicine, its potential use in Western medicine has only recently been explored. Research to date suggests that turmeric, besides having an immunomodulatory role, is also of use in preventing oxidative stress that can lead to inflammation, cancer and arthritis. The natural products in turmeric that are purported to possess health benefits include a number of curcuminoids including curcumin (C), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). A rapid HPLC method using a Thermo Fisher Scientific Dionex UltiMate 3000 electrochemical (EC) detector for the simultaneous measurement of C, DMC and BDMC was developed. Curcuminoids in three food products, including turmeric power, curry powder and a pellet curry sauce, were quantitatively determined after simple ultrasonic extraction with methanol. Separation of curcuminoids was achieved in just 3 min using a Thermo Fisher Scientific Dionex PA2 column (2.2 µm particles, 2.1 × 50 mm). With the EC detector, the LOD (S/N = 3) was 2pg (on column) for C and DMC and 4pg for BDMC; intraday precision (n = 10) was < 10% for 10pg (on column) and < 4% for 20pg curcuminoids. A comparison of different detection technologies showed that EC detection was more sensitive than UV detection, and was both more sensitive and had more uniform response when compared to fluorescence (FL) detection.

A comparative study of PNIPAM nanoparticles of curcumin, demethoxycurcumin, and bisdemethoxycurcumin and their effects on oxidative stress markers in experimental stroke

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. The present study examined the hypothesis that intranasal delivery of nanoformulation of curcuminoids would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). The rats were subjected to 2h of MCAO followed by 22h reperfusion, after which the grip strength, locomotor activity was performed. The effects of treatment in the rats were assessed by grip strength, locomotor activity and biochemical studies (glutathione peroxidase, glutathione reductase, lipid peroxidation, superoxide dismutase, and catalase) in the brain. Pretreatment with polymeric N-isopropyl acryl amide (PNIPAM) nanoparticles formulation of all three curcuminoids (curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC)) at doses (100μg/kg body weight) given intranasally was effective in bringing significant changes on all the parameters. While nanoformulation of curcumin at a dose of 100μg/kg body weight was most active in the treatment of cerebral ischemia as compared to others nanoformulation of curcuminoids. The potency of antioxidant activity significantly decreased in the order of PNIPAM nanoformulation of Cur > DMC >> BDMC, thus suggesting the critical role of methoxy groups on the phenyl ring.

Spectrofluoremetric and molecular docking study on the interaction of bisdemethoxycurcumin with bovine β-casein nanoparticles

The interaction of bisdemethoxycurcumin (BDMC), as one of the main active component of turmeric (Curcuma longa L.), with bovine β-casein nanoparticle, as an efficient drug carrier system, was investigated using steady-state fluorescence spectroscopy and molecular docking calculations. Results of fluorescence quenching experiments, Forster energy transfer measurements and molecular docking calculations suggested that BDMC bind to the hydrophobic core of β-casein via formation of 3 hydrogen bonds and several vander Waals contacts that represented the encapsulation of BDMC in β-casein micelle nanoparticles. The binding parameters including number of substantive binding sites and the binding constants were evaluated by fluorescence quenching method. Additionally, the cytotoxicity of free BDMC and BDMC-β-casein complex in human breast cancer cell line MCF7 was evaluated in vitro. The study revealed the higher cytotoxic effects of encapsulated BDMC on MCF7 cells compared to equal dose of free BDMC.

Demethoxycurcumin Inhibits Energy Metabolic and Oncogenic Signaling Pathways through AMPK Activation in Triple-Negative Breast Cancer Cells

Demethoxycurcumin (DMC), curcumin (Cur), and bisdemethoxycurcumin (BDMC) are major forms of curcuminoids found in the rhizomes of turmeric. This study examined the effects of three curcuminoid analogues on breast cancer cells. The results revealed that DMC demonstrated the most potent cytotoxic effects on breast cancer MDA-MB-231 cells. Compared with estrogen receptor (ER)-positive or HER2-overexpressing breast cancer cells, DMC demonstrated the most efficient cytotoxic effects on triple-negative breast cancer (TNBC) cells. However, nonmalignant MCF-10A cells were unaffected by DMC treatment. The study showed that DMC activated AMPK in TNBC cells. Once activated, AMPK inhibited eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) signaling and mRNA translation via mammalian target of rapamycin (mTOR) and decreased the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). DMC also targeted multiple AMPK downstream pathways. Among these, the dephosphorylation of Akt is noteworthy because it circumvents the feedback activation of Akt that results from mTOR inhibition. Moreover, DMC suppressed LPS-induced IL-6 production, thereby blocking subsequent Stat3 activation. In addition, DMC also sustained epidermal growth factor receptor (EGFR) activation by suppressing the phosphatases, PP2a and SHP-2. These results suggest that DMC is a potent AMPK activator that acts through a broad spectrum of anti-TNBC activities.

Human papilloma virus 16 e6 protein as a target for curcuminoids, curcumin conjugates and congeners for chemoprevention of oral and cervical cancers

Curcumin (diferuloyl methane) and its naturally occurring analogs viz. demethoxy, bisdemethoxy and cyclocurcumin, present in rhizomes of curcuma species turmeric, have been shown to inhibit the proliferation of a wide variety of tumor cells. Target nuclear protein HPV 16 E6 (PDB ID: 2fk4) is the major protein actively participating in oral and cervical cancers. In silico studies indicate that curcumin and its natural analogs have effective binding with different active sites on HPV 16 E6 protein, ideal target for restoring the tumor suppressor function of p53 and thus allowing the apoptosis of infected cells. The main limitation in the use of curcuminoids as therapeutic agents is their low bioavailability. Since piperine is known to enhance curcumin bioavailability to more than two thousand times by inhibiting its efflux, a conjugate of curcumin-piperic acid was also used. Although curcumin has been found to have strongest binding with this target and the two curcuminoids, demethoxy and bisdemethoxy curcumin have lower but comparable affinity, chlorogenic acid amongst the naturally occurring analogs has been found to have best binding affinity amongst all the analogs. Although curcumin-piperoyl conjugate does not show very encouraging results, it is likely to have potential activity in vitro and in vivo. These results throw light on the SAR of curcuminoids, leading to future designing of potent, non-toxic drugs for oral and cervical cancers.

Quantification of curcumin, demethoxycurcumin, and bisdemethoxycurcumin in rodent brain by UHPLC/ESI‐Q‐TOF‐MS/MS after intra‐nasal administration of curcuminoids loaded PNIPAM nanoparticles

An ultra high performance liquid chromatography-electrospray ionization-synapt mass spectrometric method (UHPLC/ESI-QTOF-MS/MS) for the analysis of curcumin (Cur), demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) in Wistar rat brain homogenate was developed and validated. The chromatographic separation was achieved on a Waters ACQUITY UPLC™ BEH C18 (2.1mm × 100 mm; 1.7μm) column using isocratic mobile phase, consisting of acetonitrile: 10mM ammonium formate: formic acid (90:10:0.05v/v/v), at a flow rate of 0.2 ml min(-1) . The transitions occurred at m/z 367.0694/217.0598, 337.0717/173.0910, 307.0760/187.0844 for Cur, DMC, BDMC and m/z 307.0344/229.0677 for the IS (Nimesulide) respectively. The recovery of the analytes from Wistar rat brain homogenate was optimized using liquid-liquid extraction technique (LLE) in (ethyl acetate: chloform) mixture. The total run time was 3.0 min and the elution of Cur, DMC, BDMC occurred at 1.6, 1.75, 1.70 min, and for the IS 1.87 min, respectively. The linear dynamic range was established over the concentration range of 1.00 ng mL(-1) to 1000.0 ng mL(-1) (r(2) ; 0.9909 ± 0.0011, 0.9911 ± 0.003, and 0.9919 ± 0.0013) for Cur, DMC, and BDMC, respectively. The intra and inter-assay accuracy in terms of % CV for Cur, DMC, and BDMC was in the range 0.47-2.20, 0.47-1.65, and0.44-2.70, respectively. The lower limit of detection (LOD) and quantitation (LOQ) for Cur, DMC, and BDMC were 0.46, 0.05, 0.16 ng mL(-1) and 0.153, 0.015, 0.052 ng mL(-1) , respectively. Analytes were stable and the method proved to be accurate (recovery, >85%), specific and was applied to evaluate the Cur, DMC, BDMC loaded PNIPAM NPs as vehicles for nose to brain drug delivery.

Biochemical Composition of Curcuma longa L. Accessions

The essential oil composition and total phenolic content (TPC) of curcuminoids were studied in rhizomes of nine Curcuma longa L. accessions. Curcuminoids, present in commercially available turmeric rhizomes, play vital roles in various pharmacological activities. A simple, rapid, and sensitive high performance liquid chromatography photodiode array (HPLC-PDA) method was optimized for simultaneous determination of curcuminoids, namely, a mixture of curcumin, demethoxy curcumin (DMC), and bisdemethoxy curcumin (BDMC) in rhizomes of C. longa. Chromatographic separation was performed on an RP C18 column within 13 minutes (11.4 to 12.95 minutes). Elution was accomplished by the application of acetonitrile and 1.5% acetic acid in water in a gradient system with flow rate of 2.0 mL min−1. PDA was employed for qualitative and quantitative analysis. The calibration curves were found linear (0.99) for all cucuminoids; the limit of detection and quantification ranged between 1.01 µ g mL−1 to 1.16 µ g mL−1 and 2.30 µ g mL−1 to 3.05 µ g mL−1, respectively, while recovery values ranged between 97.97% to 98.32%. The amount of curcumin varied from 0.46% to 2.17%, DMC from 0.13% to 0.92% and BDMC from 0.06% to 0.52%. The validated method was successively used to determine the above compounds in C. longa rhizomes. The TPC in rhizomes ranged from 14.12 mg g−1 to 27.72 mg g−1. The chemical composition of rhizome essential oil, analyzed by gas chromatography mass spectrometry (GCMS,) showed large variations in major compounds like ar-tumerone (7.31–38.66%), β-curcumene (1.58–24.53%), and curlone (1.55–15.97%).