Preparation Of Curcumin Research Articles

Demethoxycurcumin Is A Potent Inhibitor of P-Type ATPases from Diverse Kingdoms of Life.

P-type ATPases catalyze the active transport of cations and phospholipids across biological membranes. Members of this large family are involved in a range of fundamental cellular processes. To date, a substantial number of P-type ATPase inhibitors have been characterized, some of which are used as drugs. In this work a library of natural compounds was screened and we first identified curcuminoids as plasma membrane H+-ATPases inhibitors in plant and fungal cells. We also found that some of the commercial curcumins contain several curcuminoids. Three of these were purified and, among the curcuminoids, demethoxycurcumin was the most potent inhibitor of all tested P-type ATPases from fungal (Pma1p; H+-ATPase), plant (AHA2; H+-ATPase) and animal (SERCA; Ca2+-ATPase) cells. All three curcuminoids acted as non-competitive antagonist to ATP and hence may bind to a highly conserved allosteric site of these pumps. Future research on biological effects of commercial preparations of curcumin should consider the heterogeneity of the material.

Randomized Pharmacokinetic Crossover Study Comparing 2 Curcumin Preparations in Plasma and Rectal Tissue of Healthy Human Volunteers.

Curcumin is poorly absorbed, which is interest in new preparations. However, little is known about variations in its pharmacokinetics and tissue bioavailability between formulations. In this randomized, crossover study we evaluated the relationship between steady-state plasma and rectal tissue curcuminoid concentrations using standard and phosphatidylcholine curcumin extracts. There was no difference in the geometric mean plasma AUCs when adjusted for the 10-fold difference in curcumin dose between the 2 formulations. Phosphatidylcholine curcumin extract yielded only 20% to 30% plasma demethoxycurcumin and bisdemethoxycurcumin conjugates compared to standard extract, yet yielded 20-fold greater hexahydrocurcumin. When adjusting for curcumin dose, tissue curcumin concentrations were 5-fold greater for the phosphatidylcholine extract. Improvements in curcuminoid absorption due to phosphatidylcholine are not uniform across the curcuminoids. Furthermore, curcuminoid exposures in the intestinal mucosa are most likely due to luminal exposure rather than to plasma disposition. Finally, once-daily dosing is sufficient to maintain detectable curcuminoids at steady state in both plasma and rectal tissues.

Use of Meriva as complementary therapy of locally advanced or metastatic pancreatic cancer (PC) with gemcitabine (GEM).

e15696Background: GEM still represents one of the mostly adopted treatments for PC. Combination treatments provided some improvement in response rate (RR) and progression free survival (PFS), although almost invariably associated to increased toxicity. Aiming to find a complementary therapy to GEM in advanced PC, we tested a preparation of curcumin complexed with phospholipids (Meriva) to increase bioavailability. Curcumin has antinflammatory, antioxidant and potential antitumor properties, seemingly, descending from the activation of nuclear factor Nrf2 and inhibition of NFkB. From this pattern of nutraceutical effects of Curcumin, Meriva emerges as a good candidate for complementary therapy, while also improving quality of life (QoL). Methods: This was a single centre, single arm prospective phase II trial. Inclusion criteria were: previously untreated patients with histologically confirmed metastatic or locally advanced PC, ECOG performance status (PS) of 0-2, adequate organ function and written inform...

Preparation, characterization and biological evaluation of curcumin loaded alginate aldehyde–gelatin nanogels

Curcumin, a natural polyphenol exhibits chemopreventive and chemotherapeutic activities towards cancer. In order to improve the bioavailability and therapeutic efficacy, curcumin is encapsulated in alginate aldehyde–gelatin (Alg Ald-Gel) nanogels. Alginate aldehyde–gelatin nanogels are prepared by inverse miniemulsion technique. Physicochemical properties of the curcumin loaded nanogels are evaluated by, Dynamic light scattering (DLS), NMR spectroscopy and Scanning electron microscopy (SEM). Curcumin loaded nanogels show hydrodynamic diameter of 431±8nm and a zeta potential of −36±4mV. The prepared nanogels exhibit an encapsulation efficiency of 72±2%. In vitro drug release studies show a controlled release of curcumin from nanogels over a period of 48h. Hemocompatibility and cytocompatibility of the nanogels are evaluated. Bare nanogels are cytocompatible and curcumin loaded nanogels induce anticancer activity towards MCF-7 cells. In vitro cellular uptake of the curcumin loaded nanogels using confocal laser scanning microscopy (CLSM) confirms the uptake of nanogels in MCF-7 cells. Hence, the developed nanogel system can be a suitable candidate for curcumin delivery to cancer cells.

Preparation, characterization and photostability assessment of curcumin microencapsulated within methacrylic copolymers

Microencapsulated curcumin (CUR) was obtained by coevaporation with polymethacrylate polymers (blends at various percent ratios of Eudragit® RS100 and RL100 resins). The suspensions were freeze-dried to produce free flowing microparticles, which were sieved in the 420–90 μm range. They were characterized in the solid state for micromeritic properties and drug loading, and by FT-IR, powder X-ray diffractometry and differential scanning calorimetry for physical state. Encapsulation efficiency largely varied from 35 to 95%, mainly depending on the copolymer composition and to a less extent from drug-to-polymer ratio. Solid-state characterization confirmed the chemical stability of CUR in microparticles, and suggested that the drug was in a microcrystalline form within the polymer matrix; microscopy analysis confirmed the latter statement. In vitro release and dissolution profile of neat and encapsulated CUR were assessed in simulated gastric and intestinal fluids: from these studies, it was however found that the microencapsulation of CUR in these polymers did not improve the solubility of this very poorly soluble compound in simulated gastric and intestinal aqueous media.Interestingly, photostability experiments showed that the dispersion of CUR in the polymer matrix effectively protects the drug from light-induced chemical degradation, with an effect dependent on the drug-to-polymer ratio.

Preparation of Curcumin Loaded Egg Albumin Nanoparticles Using Acetone and Optimization of Desolvation Process.

In this study, acetone was used as a desolvating agent to prepare the curcumin-loaded egg albumin nanoparticles. Response surface methodology was employed to analyze the influence of process parameters namely concentration (5-15%w/v) and pH (5-7) of egg albumin solution on solubility, curcumin loading and entrapment efficiency, nanoparticles yield and particle size. Optimum processing conditions obtained from response surface analysis were found to be the egg albumin solution concentration of 8.85%w/v and pH of 5. At this optimum condition, the solubility of 33.57%, curcumin loading of 4.125%, curcumin entrapment efficiency of 55.23%, yield of 72.85% and particles size of 232.6 nm were obtained and these values were related to the values which are predicted using polynomial model equations. Thus, the model equations generated for each response was validated and it can be used to predict the response values at any concentration and pH.

Characterization and antimicrobial phototoxicity of curcumin dissolved in natural deep eutectic solvents

Natural deep eutectic solvents (NADES) are a novel class of eutectics which show a unique potential as solubilizer of water insoluble compounds. The purpose of the current study was to evaluate the potential of NADES as a solvent for the hydrophobic photosensitizer curcumin for use in antimicrobial photodynamic therapy (aPDT). Two of the seventeen NADES initially prepared (i.e., NADES GS and MC3) solubilized >0.05mg/ml curcumin and were further characterized. The hydrolytic stability (i.e., t1/2) of curcumin in NADES was comparable to or up to 2–10 times higher than previously reported results in cyclodextrins and up to >1300 times higher than results reported in buffer at pH8. The photolytic stability increased by a factor 5.6–10 in GS compared to the most photostable cyclodextrin and surfactant preparations reported previously. This NADES seemed to lock curcumin in its colorless diketo conformer, resulting in higher photostability than in ethanol and in the NADES MC3. The curcumin-NADES preparations dissolved rapidly in aqueous media and formed supersaturated solutions of curcumin. Precipitation of curcumin was observed after ≤1h depending on the dilution factor (pH<8). The NADES MC3 containing curcumin photoinactivated Escherichia coli at a lower curcumin concentration (1.25μM) than in any previously investigated preparations of curcumin. The ability of NADES to lock curcumin within one specific molecular conformation and also to potentiate the phototoxic effect of this photosensitizer emphasizes the unique properties of the NADES as a solvent.

Abstract CT124: A phase II randomized double blind study of curcumin with preoperative capecitabine and radiation therapy followed by surgery for rectal cancer

Abstract Introduction: In vivo studies show that curcumin, a component of turmeric (Curcuma longa), inhibits signal transduction pathways involved in tumor growth and angiogenesis, induces apoptosis and potentiates the radioresponse of cancer cells by inducing NF-kB activity. However no study has validated its anti-tumor effect in patients undergoing cancer treatment. We performed a randomized double blinded study in patients with locally advanced rectal cancer to assess the efficacy of a combination of capecitabine and radiation therapy with or without curcumin, using pathological complete response (pCR) rate as a surrogate for overall clinical outcomes. Patients and Methods: Between September, 2008 and September, 2010, patients with biopsy-proven, locally advanced adenocarcinoma of the rectum were enrolled and randomized to placebo and curcumin treatment arms in a 1:2 ratio. All patients received pre-operative radiation therapy (50.4 Gy/28 fractions for 5-6 weeks) along with concurrent capecitabine (825 mg/m2 orally twice daily, only on days of radiation) followed by surgery after 6 weeks. Curcumin or placebo capsules (4 g orally, twice daily) were given throughout the chemoradiation therapy period and until surgery, typically 6 weeks later. Patients were evaluated at baseline, weekly during chemoradiation and just before surgery using the MD Anderson symptom inventory (MDASI) and Brief Fatigue Inventory (BFI) questionnaires. In addition, weekly clinical assessment and monitoring of hematological and biochemical parameters was done throughout the treatment course to evaluate treatment-related toxicity. The pharmacokinetics of curcumin was studied using blood samples taken before and one hour after curcumin intake during the second week of chemoradiation. The primary target outcome was pCR evaluated at the time of surgery. This study is registered with Clinicaltrials.gov, number NCT00745134. Results: 22 patients were enrolled in the study and 15 received curcumin. The median age was 61 years and majority were males (13, 59%). The median serum curcumin concentrations before and one hour after curcumin intake did not differ significantly (p = 0.33) and were 3.04 ng/mL (range, 1.24 to 18.88) and 3.32 ng/mL (range, 0.84 to 5.36) respectively. pCR was seen in two patients in the placebo arm and one patient in the curcumin arm (p = 0.23). Acute toxicity was relatively uncommon in both groups: grade 2 diarrhea (1, 7%), grade 2 dermatitis (5, 33%) and grade 3 diarrhea (1, 7%) in the curcumin arm; grade 2 dermatitis (1, 14%) and grade 3 diarrhea (1, 14%) in the placebo arm. Conclusion: Addition of curcumin to capecitabine and radiation therapy did not increase the rate of pCR in patients with rectal cancer. The low bioavailability of curcumin preparation used could explain the lack of efficacy noted in this study. Citation Format: Awalpreet S. Chadha, Sushovan Guha, Sunil Krishnan. A phase II randomized double blind study of curcumin with preoperative capecitabine and radiation therapy followed by surgery for rectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT124. doi:10.1158/1538-7445.AM2015-CT124

Study of curcumin behavior in two different lipid bilayer models of liposomal curcumin using molecular dynamics simulation

Liposomal formulation of curcumin is an important therapeutic agent for the treatment of various cancers. Despite extensive studies on the biological effects of this formulation in cancer treatment, much remains unknown about curcumin–liposome interactions. Understanding how different lipid bilayers respond to curcumin molecule may help us to design more effective liposomal curcumin. Here, we used molecular dynamics simulation method to investigate the behavior of curcumin in two lipid bilayers commonly used in preparation of liposomal curcumin, namely dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylglycerol (DMPG). First, the free energy barriers for translocation of one curcumin molecule from water to the lipid bilayer were determined by using the potential of mean force (PMF). The computed free energy profile exhibits a global minimum at the solvent–headgroup interface (LH region) for both lipid membranes. We also evaluated the free energy difference between the equilibrium position of curcumin in the lipid bilayer and bulk water as the excess chemical potential. Our results show that curcumin has the higher affinity in DMPG compared to DPPC lipid bilayer (−8.39 vs. −1.69 kBT) and this is related to more hydrogen bond possibility for curcumin in DMPG lipid membrane. Next, using an unconstrained molecular dynamic simulation with curcumin initially positioned at the center of lipid bilayer, we studied various properties of each lipid bilayer system in the presence of curcumin molecule that was in full agreement with PMF and experimental data. The results of these simulation studies suggest that membrane composition could have a large effect on interaction of curcumin–lipid bilayer.

Separation and purification of curcumin preparation of morphology controlled micro particles

Curcumin was extracted from turmeric plants which is the most commonly used natural pigments, and possess a variety of pharmacological functions except for using pigment. The morphology and particle size of curcumin are main factors affecting the application. Therefore, the morphology and particle size distribution of curcumin were effectively controlled by advanced technology, which is significant for expanding the application and added value of curcumin. The curcumin crystal was obtained from curcumin pigments by using column chromatography and recrystallization techniques. The composition and structure of curcumin were characterized by elementary analysis, UV-Vis, IR and NMR. Micronization of curcumin was carried out the Solution Enhanced Dispersion by Supercritical Fluids (SEDS) technology. In the process, supercritical carbon dioxide was used as anti-solvent and acetone/dichloromethane (1:4, v:v) was used as solvent. The curcumin crystals with PSs of about 378 μm were successfully micronized by the SEDS process to micro particles with PSs of about 2.6-10 μm. The acicular, leaves, dendritic and tubular micro particles were obtained through controlling parameters such as pressure, temperature, solution concentration and solution flow rate.DOI: http://doi.dx.org/10.5564/mjc.v15i0.314 Mongolian Journal of Chemistry 15 (41), 2014, p11-14

A new curcuma extract (flexofytol®) in osteoarthritis: results from a belgian real-life experience.

This retrospective observational study summarizes the experiences of 820 patients treated with a new Curcuma extract (Flexofytol®, 4-6 capsules per day), for more than 6 months for various forms of painful osteoarthritis. These experiences were reported by 110 Belgian general practitioners via a questionnaire that included quality-of-life parameters for assessing patient experience. Data were submitted to an independent statistician for analysis. Within the first 6 weeks, Flexofytol® improved patient pain, articular mobility, and quality of life. Excellent tolerance was reported, and more than half of these patients were able to discontinue analgaesic and anti-inflammatory drugs. Patient satisfaction was confirmed by their decision to maintain Flexofytol® therapy for more than 6 months. These data must be confirmed with randomized controlled studies. We currently conclude that Flexofytol® which is based on a new preparation of curcumin, is as a potential neutraceutical for the care of patients complaining of joint problems, with excellent tolerance and rapid benefits for articular mobility, pain, and quality of life.

Effectiveness of topical curcumin for treatment of mastitis in breastfeeding women: a randomized, double-blind, placebo-controlled clinical trial.

To determine the efficacy of topical curcumin in reducing breast inflammation in women suffering from lactational mastitis. A randomized double-blind, placebo-controlled study including 63 breastfeeding women with lactational mastitis were randomly assigned to receive curcumin topical cream, one pump every 8 hours for 3 days (n=32) or topical moisturizer as placebo (n=31). Using an index for severity of breast inflammation, all of the patients had moderate breast inflammation before entering the study. The outcome of treatment was evaluated using the same index at 24, 48 and 72 hours of starting the treatment. There was no significant difference between two study groups regarding the baseline characteristics such as age (p=0.361) and duration of lactation (p=0.551). After 72-hour of therapy, patients in curcumin groups had significantly lower rate of moderate (p=0.019) and mild (p=0.002) mastitis. Patients in curcumin group had significantly lower scores for tension (p<0.001), erythema (p<0.001) and pain (p<0.001), after 72-hour of treatment. The results of the current study indicate that topical preparation of curcumin successfully decrease the markers of lactational mastitis such as pain, breast tension and erythema within 72 hours of administration without side effects. Thus, topical preparation of curcumin could be safely administered for those suffering from lactational mastitis after excluding infectious etiologies.

Simple and effective preparation of nano-pulverized curcumin by femtosecond laser ablation and the cytotoxic effect on C6 rat glioma cells in vitro

The pulverization of poorly water-soluble drugs and drug candidates into nanoscale particles is a simple and effective means of increasing their pharmacological effect. Consequently, efficient methods for pulverizing compounds are being developed. Femtosecond lasers, which emit ultrashort laser pulses, can be used to generate nanoscale particles without heating and are finding in various fields, including pharmaceutical science. Laser ablation holds promise as a novel top-down pulverization method for obtaining drug nanoparticles. We used a poorly water-soluble compound, curcumin (diferuloyl methane), to understand the characteristics of femtosecond laser pulverization. Various factors such as laser strength, laser scan speed, and the buffer solution affected the size of the curcumin particles. The minimum curcumin particle size was approximately 500 nm; the particle size was stable after 30 days. In vitro studies suggested that curcumin nanoparticles exhibited a cytotoxic effect on C6 rat glioma cells, and remarkable intracellular uptake of the curcumin nanoparticles was observed. The results suggest that femtosecond laser ablation is a useful approach for preparing curcumin nanoparticles that exhibit remarkable therapeutic effects.

High Yield and High Loading Preparation of Curcumin–PLGA Nanoparticles Using a Modified Supercritical Antisolvent Technique

A modified supercritical antisolvent method, aiming at high yielding and high loading, is developed for preparation of drug-loaded polymeric nanoparticles. The modified method consists of three alternate stages: injecting solution via a nozzle into a precipitation vessel filled with supercritical CO2, static agitation, and washing of precipitated particles with supercritical CO2. The process stages are continuously repeated until ending injection of a desired amount of solution. The ultrasound operates during the entire process. Poly(lactic-co-glycolic acid) (PLGA) and curcumin are model components. The influences of the process parameters on the yielding and loading are investigated. The maximum yield of the curcumin–PLGA nanoparticles 50 nm in size and the curcumin loading in it reach 96% and 45%, respectively. High yield, high loading, and uniform size are attributed to the efficient mixing between solution droplets and antisolvent, and sequential washing using an antisolvent under ultrasonic agitation. Experimental data are fitted and optimized by neural network simulation.

Preparation, characterisation and evaluation of curcumin with piperine-loaded cubosome nanoparticles

Objective: In this study, curcumin was designed into the nanoformulation called cubosome with piperine in order to improve oral bioavailability and tissue distribution of curcumin. Methods: The characteristic of the cubosome was studied by using scanning electron microscope (SEM), Infrared spectrum and small angle X-ray scattering (SAXS) techniques. Tissue distribution of cubosome was measured by liquid chromatography-mass spectrometry (LC-MS) method in mice. Results: The characteristic of the cubosome was demonstrated that the curcumin and piperine were encapsulated in the interior of the cubosome and the crystal form was Pn3m space. The pharmacokinetic test revealed that the cubosome could improve the oral bioavailability significantly compared to the suspension of curcumin with piperine and be mainly absorbed by the spleen. Conclusion: These findings provide the reference to a preferable choice of the curcumin formulation and contribute to therapeutic application in clinical research.

Preparation and characterization of electrospun curcumin loaded poly(2-hydroxyethyl methacrylate) nanofiber-A biomaterial for multidrug resistant organisms

Curcumin loaded poly(2-hydroxy ethyl methacrylate) p(HEMA) nanofiber were produced using electrospinning method and characterized. The nanofibrous scaffold supports good cell growth, attachment and retains its original morphology. Sustained and controlled release pattern of curcumin seen to be efficient against infectious disease caused by multidrug resistant organisms. Antibacterial activity of curcumin against Methicillin resistant staphylococcus aureus (MRSA) and extended spectrum β lactamase (ESBL) proved to be a good alternate herbal compound for antibiotics. Hence the results indicate p(HEMA) nanofiber loaded with curcumin have potential to use as patch in wound healing of infectious disease caused by multidrug resistant organisms and excellent drug delivery vessel.

Curcumin: New Weapon against Cancer

All the evidences point out to the fact that the incidence, mortality and number of persons living with cancer are on the rise and, thus, this will impose a significant burden on health care resources. The considerable number of deaths from cancer necessitates the need to developing novel alternative cures that are efficient, safe, cheap and easy to use. In the search for new therapies for tumors, naturally-derived compounds have been considered as a good source of novel anticancer drugs. The challenge here is to find products that are pharmacologically active against tumor cells with suitable toxicity profile and least damage to normal cells. Curcumin is a spice widely used in many countries especially in South Asia and it has gained importance for its anticancer function and low toxicity toward normal tissues in a range of biological systems. In spite of significant research works, many difficulties hinder its oral use in the therapy of different kind of tumors, such as extreme low solubility in water, quick break down and excretion after being absorbed in the human body. Low bioavailability due to enhanced metabolism and rapid system elimination is another problem that hinders oral use of curcumin as anticancer agent. Therefore, the previously mentioned poor pharmacokinetics characteristics inhibit curcumin from reaching its site of action and, thus, lessen its effectiveness against tumors. This article reviews the latest global cancer statistics with special attention to be directed toward ovarian cancer. It sheds light on many research works that investigated the protective and therapeutic functions of different curcumin preparations against different sites of cancer using animal models. It also summarizes recent research works concerning the antitumor effects of curcumin alone and/or loaded into a range of delivery devices in many types of ovarian cancer cell lines. In the last section, it discusses the latest research work with regard ovarian cancer in the kingdom of Saudi Arabia.

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

This review addresses the oncopharmacological properties of curcumin at the molecular level. First, the interactions between curcumin and its molecular targets are addressed on the basis of curcumin's distinct chemical properties, which include H-bond donating and accepting capacity of the β-dicarbonyl moiety and the phenylic hydroxyl groups, H-bond accepting capacity of the methoxy ethers, multivalent metal and nonmetal cation binding properties, high partition coefficient, rotamerization around multiple C-C bonds, and the ability to act as a Michael acceptor. Next, the in vitro chemical stability of curcumin is elaborated in the context of its susceptibility to photochemical and chemical modification and degradation (e.g., alkaline hydrolysis). Specific modification and degradatory pathways are provided, which mainly entail radical-based intermediates, and the in vitro catabolites are identified. The implications of curcumin's (photo)chemical instability are addressed in light of pharmaceutical curcumin preparations, the use of curcumin analogues, and implementation of nanoparticulate drug delivery systems. Furthermore, the pharmacokinetics of curcumin and its most important degradation products are detailed in light of curcumin's poor bioavailability. Particular emphasis is placed on xenobiotic phase I and II metabolism as well as excretion of curcumin in the intestines (first pass), the liver (second pass), and other organs in addition to the pharmacokinetics of curcumin metabolites and their systemic clearance. Lastly, a summary is provided of the clinical pharmacodynamics of curcumin followed by a detailed account of curcumin's direct molecular targets, whereby the phenotypical/biological changes induced in cancer cells upon completion of the curcumin-triggered signaling cascade(s) are addressed in the framework of the hallmarks of cancer. The direct molecular targets include the ErbB family of receptors, protein kinase C, enzymes involved in prostaglandin synthesis, vitamin D receptor, and DNA.

Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis — A randomized, placebo-controlled, pilot study

Background and aimsCurcumin, an active ingredient of turmeric with anti-inflammatory properties, has been demonstrated to be useful in experimental models of ulcerative colitis (UC). It's efficacy in humans needs to be investigated. MethodsA randomized, double-blind, single-centre pilot trial was conducted in patients with distal UC (<25cm involvement) and mild-to-moderate disease activity. Forty-five patients were randomized to either NCB-02 (standardized curcumin preparation) enema plus oral 5-ASA or placebo enema plus oral 5-ASA. Primary end point was disease response, defined as reduction in Ulcerative Colitis Diseases Activity Index by 3 points at 8weeks, and secondary end points were improvement in endoscopic activity and disease remission at 8weeks. ResultsResponse to treatment was observed in 56.5% in NCB-02 group compared to 36.4% (p=0.175) in placebo group. At week 8, clinical remission was observed in 43.4% of patients in NCB-02 group compared to 22.7% in placebo group (p=0.14) and improvement on endoscopy in 52.2% of patients in NCB-02 group compared to 36.4% of patients in placebo group (p=0.29). Per protocol analysis revealed significantly better outcomes in NCB-02 group, in terms of clinical response (92.9% vs. 50%, p=0.01), clinical remission (71.4% vs. 31.3%, p=0.03), and improvement on endoscopy (85.7% vs. 50%, p=0.04). ConclusionIn this pilot study we found some evidence that use of NCB-02 enema may tend to result in greater improvements in disease activity compared to placebo in patients with mild-to-moderate distal UC. The role of NCB-02 as a novel therapy for UC should be investigated further.

Curcumin analogue identified as hyaluronan export inhibitor by virtual docking to the ABC transporter MRP5

Hyaluronan is overproduced in many diseases including metastasis, inflammation or ischemia, but there is no drug to attenuate hyaluronan production. Hyaluronan is exported from fibroblasts by the multidrug resistance associated protein 5 (MRP5) which is inhibited by the plant phenols curcumin or xanthohumol. We performed virtual docking and chemical synthesis of analogues to optimize the inhibitors. The AutoDock software was used to identify the binding cavity within the open conformation of MRP5. Inhibitory plant phenols bound to the ATP binding site between the two nucleotide binding domains NBD1 and NBD2. This binding cavity was chosen to screen about 120 derivatives and analogues. The superior hyaluronan export inhibitor was 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (hylin). It inhibited hyaluronan export from fibroblasts with an IC50 of 4.9 μM. Hylin is a minor component in natural curcumin preparations and has previously been described as anti-metastatic and anti-inflammatory. Since curcumin itself is unstable under physiological conditions, the active component for many cell biological and pharmaceutical effects of natural curcumin preparations could be hylin that acts by hyaluronan export inhibition.