Rational Design of Molecularly Imprinted Polymers for Curcuminoids Binding: Computational and Experimental Approaches for the Selection of Functional Monomers.

Molecularly imprinted polymers (MIPs) have emerged as bespoke materials with versatile molecular applications. In this study, we propose a proof of concept for a methodology employing molecular dynamics (MD) simulations to guide the selection of functional monomers for curcuminoid binding in MIPs. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin are phenolic compounds widely employed as spices, pigments, additives, and therapeutic agents, representing the three main curcuminoids of interest. Through MD simulations, we investigated prepolymerization mixtures composed of various functional monomers, including acrylamide (ACA), acrylic acid (AA), methacrylic acid (MAA), and N-vinylpyrrolidone (NVP), with ethylene glycol dimethacrylate (EGDMA) as the cross-linker and acetonitrile as the solvent. Curcumin was selected as the template molecule due to its structural similarity to the other curcuminoids. Notably, the prepolymerization mixture containing NVP as the functional monomer demonstrated superior molecular recognition capabilities toward curcumin. This observation was supported by higher functional monomer molecules surrounding the template, a lower total nonbonded energy between the template and monomer, and a greater number of hydrogen bonds in the aggregate. These findings suggest a stronger affinity between the functional monomer NVP and the template. We synthesized, characterized, and conducted binding tests on the MIPs to validate the MD simulation results. The experimental binding tests confirmed that the MIP-NVP exhibited higher binding capacity. Consequently, based on MD simulations, our computational methodology effectively guided the selection of the functional monomer, leading to MIPs with binding capacity for curcuminoids. The outcomes of this study provide a valuable reference for the rational design of MIPs through MD simulations, facilitating the selection of components for MIPs. This computational approach holds the potential for extension to other templates, establishing a robust methodology for the rational design of MIPs.

Curcumin modulates astrocyte function under basal and inflammatory conditions.

Curcumin is a pleiotropic molecule with well-known anti-inflammatory effects. This molecule has attracted attention due to its capacity to pass the blood-brain-barrier and modulate central nervous system (CNS) cells, such as astrocytes. Astrocytes are the most numerous CNS cells, and play a pivotal role in inflammatory damage, a common feature in neurodegenerative diseases such as Alzheimer's Disease. Although the actions of curcumin have been studied extensively in peripheral cells, few studies have investigated the effect of curcumin on astrocytes under basal and inflammatory conditions. The aim of this study was to characterize the effect of curcumin on astrocytic function (glutamatergic metabolism, GFAP and S100B), and investigate a possible synergic effect with another molecule, piperine. For this purpose, we used primary cultured astrocytes; our results showed that curcumin increases GSH and GFAP content, but decreases S100B secretion under basal conditions. Under inflammatory conditions, provoked by lipopolysaccharide (LPS), curcumin and piperine reversed the LPS-induced secretion of TNF-α, and piperine reverted the LPS-induced upregulation of GFAP content. Interestingly, curcumin decreases S100B secretion even more than LPS. These results highlight important context-dependent effects of curcumin and piperine on astrocytes. Although we did not observe synergic effects of co-treatment with curcumin and piperine, their effects were complementary, as piperine modulated GFAP content under inflammatory conditions, and curcumin modulated S100B secretion. Both curcumin and piperine had important anti-inflammatory actions in astrocytes. We herein provide new insights into the actions of curcumin in the CNS that may aid in the search for new molecular targets and possible treatments for neurological diseases.

Curcumin-Added Whey Protein Positively Modulates Skeletal Muscle Inflammation and Oxidative Damage after Exhaustive Exercise.

(1) Background: Exhaustive exercise can induce muscle damage. The consumption of nutritional compounds with the ability to positively influence the oxidative balance and an exacerbated inflammatory process has been previously studied. However, little is known about the nutritional value of curcumin (CCM) when mixed with whey protein concentrate (WPC). This study was developed to evaluate the effect of CCM-added WPC on inflammatory and oxidative process control and histopathological consequences in muscle tissue submitted to an exhaustive swimming test (ET). (2) Methods: 48 animals were randomly allocated to six groups (n = 8). An ET was performed 4 weeks after the start of the diet and animals were euthanized 24 h post ET. (3) Results: WPC + CCM and CCM groups reduced IL-6 and increased IL-10 expression in muscle tissue. CCM reduced carbonyl protein after ET compared to standard AIN-93M ET and WPC + CCM ET diets. Higher nitric oxide concentrations were observed in animals that consumed WPC + CCM and CCM. Consumption of WPC + CCM or isolated CCM reduced areas of inflammatory infiltrate and fibrotic tissue in the muscle. (4) Conclusions: WPC + CCM and isolated CCM contribute to the reduction in inflammation and oxidative damage caused by the exhaustive swimming test.

Curcumin Modifies the Activity of Plasmatic Antioxidant Enzymes and the Hippocampal Oxidative Profile in Rats upon Acute and Chronic Exposure to Ozone.

Ozone (O3) is an oxidating tropospheric pollutant. When O3 interacts with biological substrates, reactive oxygen and nitrogen species (RONS) are formed. Severe oxidative damage exhausts the endogenous antioxidant system, which leads to the decreased activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Curcumin (CUR) is a natural polyphenol with well-documented antioxidant and anti-inflammatory properties. The aim of this work is to evaluate the effects of curcumin on CAT, GPx, and SOD activity and the inhibition of oxidative damage after the acute and chronic exposure to O3. Fifty male Wistar rats were divided into five experimental groups: the intact control, CUR-fed control, exposed-to-O3 control, CUR-fed (preventive), and CUR-fed (therapeutic) groups. These two last groups received a CUR-supplemented diet while exposed to O3. These experiments were performed during acute- and chronic-exposure phases. In the preventive and therapeutic groups, the activity of plasma CAT, GPx, and SOD was increased during both exposure phases, with slight differences; concomitantly, lipid peroxidation and protein carbonylation were inhibited. For this reason, we propose that CUR could be used to enhance the activity of the antioxidant system and to diminish the oxidative damage caused by exposure to O3.

Ivermectin and curcumin cause plasma membrane rigidity in Leishmania amazonensis due to oxidative stress.

Spin label electron paramagnetic resonance (EPR) spectroscopy was used to study the mechanisms of action of ivermectin and curcumin against Leishmania (L.) amazonensis promastigotes. EPR spectra showed that treatment of the parasites with both compounds results in plasma membrane rigidity due to oxidative processes. With the IC50 and EPR measurements for assays using different parasite concentrations, estimations could be made for the membrane-water partition coefficient (KM/W), and the concentration of the compound in the membrane (cm50) and in the aqueous phase (cw50), which inhibits cell growth by 50%. The KM/W values indicated that ivermectin has a greater affinity than curcumin for the parasite membrane. Therefore, the activity of ivermectin was higher for experiments with low cell concentrations, but for concentrations greater than 1.5 × 108 parasites/mL the compounds did not show significantly different results. The cm50 values indicated that the concentration of compound in the membrane leading to growth inhibition or membrane alteration is approximately 1 M for both ivermectin and curcumin. This high membrane concentration suggests that many ivermectin molecules per chlorine channel are needed to cause an increase in chlorine ion influx.

Curcuma as an adjuvant in colorectal cancer treatment.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and mostly affects men. Around 20% of its incidence is by familiar disposition due to hereditary syndromes. The CRC treatment involves surgery and chemotherapy; however, the side effects of treatments and the fast emergence of drug resistance evidence the necessity to find more effective drugs. Curcumin is the main polyphenol pigment present in Curcuma longa, a plant widely used as healthy food with antioxidant properties. Curcumin has synergistic effects with antineoplastics such as 5-fluorouracil and oxaliplatin, as well anti-inflammatory drugs by inhibiting cyclooxygenase-2 and the Nuclear factor kappa B. Furthermore, curcumin shows anticancer properties by inhibition of the Wnt/ß-catenin, Hedgehog, Notch, and the phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways implicated in the progression of CRC. However, the consumption of pure curcumin is less suitable, as the absorption is poor, and the metabolism and excretion are high. Pharmacological formulations and essential oils of the plant improve the curcumin absorption, resulting in therapeutical dosages. Despite the evidence obtained in vitro and in vivo, clinical studies have not yet confirmed the therapeutic potential of curcumin against CRC. Here we reviewed the last scientific information that supports the consumption of curcumin as an adjuvant for CRC therapy.

PPAR Gamma: From Definition to Molecular Targets and Therapy of Lung Diseases.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that regulate the expression of genes related to lipid and glucose metabolism and inflammation. There are three members: PPARα, PPARß or PPARγ. PPARγ have several ligands. The natural agonists are omega 9, curcumin, eicosanoids and others. Among the synthetic ligands, we highlight the thiazolidinediones, clinically used as an antidiabetic. Many of these studies involve natural or synthetic products in different pathologies. The mechanisms that regulate PPARγ involve post-translational modifications, such as phosphorylation, sumoylation and ubiquitination, among others. It is known that anti-inflammatory mechanisms involve the inhibition of other transcription factors, such as nuclear factor kB(NFκB), signal transducer and activator of transcription (STAT) or activator protein 1 (AP-1), or intracellular signaling proteins such as mitogen-activated protein (MAP) kinases. PPARγ transrepresses other transcription factors and consequently inhibits gene expression of inflammatory mediators, known as biomarkers for morbidity and mortality, leading to control of the exacerbated inflammation that occurs, for instance, in lung injury/acute respiratory distress. Many studies have shown the therapeutic potentials of PPARγ on pulmonary diseases. Herein, we describe activities of the PPARγ as a modulator of inflammation, focusing on lung injury and including definition and mechanisms of regulation, biological effects and molecular targets, and its role in lung diseases caused by inflammatory stimuli, bacteria and virus, and molecular-based therapy.

Computational Evaluation of Interaction Between Curcumin Derivatives and Amyloid-ß Monomers and Fibrils: Relevance to Alzheimer's Disease.

BACKGROUND: The most important hallmark in the neuropathology of Alzheimer's disease (AD) is the formation of amyloid-ß (Aß) fibrils due to the misfolding/aggregation of the Aß peptide. Preventing or reverting the aggregation process has been an active area of research. Naturally occurring products are a potential source of molecules that may be able to inhibit Aß42 peptide aggregation. Recently, we and others reported the anti-aggregating properties of curcumin and some of its derivatives in vitro, presenting an important therapeutic avenue by enhancing these properties. OBJECTIVE: To computationally assess the interaction between Aß peptide and a set of curcumin derivatives previously explored in experimental assays. METHODS: The interactions of ten ligands with Aß monomers were studied by combining molecular dynamics and molecular docking simulations. We present the in silico evaluation of the interaction between these derivatives and the Aß42 peptide, both in the monomeric and fibril forms. RESULTS: The results show that a single substitution in curcumin could significantly enhance the interaction between the derivatives and the Aß42 monomers when compared to a double substitution. In addition, the molecular docking simulations showed that the interaction between the curcumin derivatives and the Aß42 monomers occur in a region critical for peptide aggregation. CONCLUSION: Results showed that a single substitution in curcumin improved the interaction of the ligands with the Aß monomer more so than a double substitution. Our molecular docking studies thus provide important insights for further developing/validating novel curcumin-derived molecules with high therapeutic potential for AD.

Phenolic Compounds Cannabidiol, Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells.

Anticancer activity of different phenols is documented, but underlying mechanisms remain elusive. Recently, we have shown that cannabidiol kills the cells of acute lymphoblastic leukemia (ALL) by a direct interaction with mitochondria, with their consequent dysfunction. In the present study, cytotoxic effects of several phenolic compounds against human the T-ALL cell line Jurkat were tested by means of resazurin-based metabolic assay. To unravel underlying mechanisms, mitochondrial membrane potential (∆Ψm) and [Ca2+]m measurements were undertaken, and reactive oxygen species generation and cell death were evaluated by flow cytometry. Three out of eight tested phenolics, cannabidiol, curcumin and quercetin, which displayed a significant cytotoxic effect, also dissipated the ∆Ψm and induced a significant [Ca2+]m increase, whereas inefficient phenols did not. Dissipation of the ∆Ψm by cannabidiol was prevented by cyclosporine A and reverted by Ru360, inhibitors of the permeation transition pore and mitochondrial Ca2+ uniporter, respectively. Ru360 prevented the phenol-induced [Ca2+]m rise, but neither cyclosporine A nor Ru360 affected the curcumin- and quercetin-induced ∆Ψm depolarization. Ru360 impeded the curcumin- and cannabidiol-induced cell death. Thus, all three phenols exert their antileukemic activity via mitochondrial Ca2+ overload, whereas curcumin and quercetin suppress the metabolism of leukemic cells by direct mitochondrial uncoupling.

Feed contaminated by fumonisin (Fusarium spp.) in chicks has a negative influence on oxidative stress and performance, and the inclusion of curcumin-loaded nanocapsules minimizes these effects.

The aim of this study was to determine whether the addition of curcumin (free and encapsulated) to chick feed would minimize the negative effects on health and performance caused by daily intake of fumonisin. We used 50 birds, divided into five treatments: CP, basal diet with 600 mg/kg of fumonisin, with antibiotic and coccidiostatic agent; CU, 600 mg/kg of fumonisin and 50 mg/kg of curcumin; NC5, feed with 600 mg/kg of fumonisin and 5 mg of nano-curcumin/kg of feed; NC10, feed with 600 mg/kg of fumonisin and 10 mg of nano-curcumin/kg of feed; and CN, fumonisin-free diet, with antibiotic and coccidiostatic. We measured weights, weight gain, and serum biochemistry, as well as antioxidant and oxidant activities. Lower body weight and weight gain were observed in chicks that received feed with fumonisin; curcumin did not minimize this negative effect. Lower glucose and triglyceride levels were also observed in the NC10 group, while the highest cholesterol levels were observed in all groups of birds that consumed fumonisin compared to the CN group. Uric acid levels were significantly lower in CP than in CN. Levels of liver enzymes were higher in CP than in CN. The highest levels of thiobarbituric acid reactive substances were found in CP and CU, whereas ROS was higher in CU compared to CN. Superoxide dismutase activity was significantly lower in CP, while glutathione S-transferase activity was higher in the CP group. Catalase activity was lower in groups of birds that consumed fumonisin compared to CN. Taken together, these findings suggest that intake of curcumin-loaded nanocapsules (10 mg/kg) had hepaprotective and antioxidant effects in chicks artificially intoxicated with fumonisin, minimizing the negative effects caused by this mycotoxin.

Dog food production using curcumin as antioxidant: effects of intake on animal growth, health and feed conservation.

The objectives of this study were to produce dog food containing curcumin replacing synthetic antioxidants, to evaluate its beneficial effects on animal growth and health. Curcumin (100 mg/kg) was added after the extrusion process along with the other micronutrients. The final concentration of curcumin was 32.9 mg/kg. The control feed was composed of the same ingredients without curcumin. After a storage of 6 months, feed composition and pH did not differ; however, the feed with curcumin showed lower protein oxidation, lipid peroxidation and higher total antioxidant capacity. After 2 months of feed production, 12 young Beagle dogs received either curcumin-containing food (n = 6)  or the control diet (n = 6). The animals were fed twice a day using individual kennels. Blood samples were taken on d 1, 35 and 42. During the first 30 d of the study, the animals had natural infectious diseases that were controlled with anti-protozoals and antibiotics. Greater numbers of red blood cells were observed in dogs fed with curcumin (d 35 and 45), and there were greater numbers of white blood cells as a consequence of increased neutrophils on d 42. At the end of the experiment, a significant reduction in the number of lymphocytes was observed in dogs that ingested curcumin (d 42), suggesting an anti-inflammatory effect, manifested as a decrease in globulin levels. In the final 15 d of the experiment, the animals were clinical healthy. Higher serum levels of glucose, urea, triglycerides and cholesterol were observed in dogs fed with curcumin. Curcumin increased the activity of several antioxidant enzymes in addition to non-protein thiols and the total antioxidant capacity in the serum, consequently reducing levels of oxygen reactive species. Curcumin supplementation of dogs did not favour growth or weight gain. Neverthless, it was concluded that curcumin improved animal health, with emphasis on the stimulation of the antioxidant system and evidence of an anti-inflammatory effect.

Recent Advances in the Development of "Curcumin Inspired" Compounds as New Therapeutic Agents.

Despite a huge body of research in the past two decades investigating the antioxidant, antiinflammatory, anti-microbial, and anti-carcinogenic properties of curcumin (CUR), a CUR-based antitumor drug is yet to be developed. Lack of success in achieving this goal stems from CUR's unfavorable biophysicochemical features, particularly poor solubility, low bioavailability, and rapid metabolism, coupled with a complex biological profile making it difficult to determine its mechanism of action. A significant body of literature aimed at improving its physicochemical properties through synthesis or by designing delivery methods has been published, and the progress in these areas has been reviewed. The present review aims to summarize recent progress in the synthesis of structurally diverse "curcumin-inspired" compounds along with computational docking and bioassay studies, through which a number of promising analogs have been identified that warrant further study.

Curcumin and silver nanoparticles carried out from polysaccharide-based hydrogels improved the photodynamic properties of curcumin through metal-enhanced singlet oxygen effect.

Colorectal cancer (CRC) has a high incidence and resistance to conventional treatments. Curcumin (CUR) is a promising natural product in the treatment of CRC with excellent in vitro results. However, its low bioavailability is a limiting factor in clinical applications. To overcome, CUR was incorporated into hydrogels constituted by chitosan (CHT) and chondroitin sulfate (CS), natural biopolymers, capable of controlled release. Hydrogels were synthesized in ionic liquids (ILs, [Hmim][HSO4]) improving the solubility of CHT and the hydrogel properties. Furthermore, CUR was combined with silver nanoparticles (AgNPs) and visible light by Photodynamic Therapy (PDT), which, through the MEO effect (Metal-Enhanced Singlet Oxygen), leads to cell death. It is highlighted the green synthesis of AgNPs using an ultrasound bath. The CHT/CS hydrogels loaded with CUR/AgNPs were properly characterized. Cellular assays showed that the hydrogels (CHT/CS) were not cytotoxic to healthy tissues. However, PDT selective illumination led to inhibition of Caco-2 human colon cancer cells by the CHT/CS/CUR-AgNPs (CC50 = 91.5 µg mL-1 of hydrogel). The cellular uptake assays showed, in addition to the therapeutic action, that the CUR can works as a diagnostic fluorescence probe (theranostic system). Finally, we highlight our commitment to work with reagents, solvents, and methodologies aiming at the principles of green chemistry.

Self-assembled peptide dendrigraft supraparticles with potential application in pH/enzyme-triggered multistage drug release.

Multistage delivery systems with size reduction capacity have been proposed as a powerful strategy for improving tissue drug penetration. Here we developed a simple and fast supramolecular approach to construct size-shrinkable polyamine-salt aggregates by ionic cross-linking of biodegradable poly-L-lysine dendrigraft with tripolyphosphate anion. The use of a peptide dendrimer as a nanobuilding block (∼7 nm in diameter) allows the formation of supraparticles (SPs) with well-defined dimensions (∼200 nm in diameter), narrow size distribution and great capacity to encapsulate different molecules, including chemotherapeutic agents as Curcumin and Doxorubicin. When exposed to slightly acidic environments, the crosslinked matrix is instantaneously disassembled to free dendrimer units. Subsequently, model cargo molecules entrapped in the dendrimer architecture can be released by the action of trypsin enzyme through peptide biodegradation. Therefore, these SPs with proved sequential pH and enzyme-responsiveness could be exploited as nanocarriers in multistage drug delivery systems.

Curcumin-micellar casein multisite interactions elucidated by surface plasmon resonance.

Determine the thermodynamic and kinetic parameters of interaction between micellar casein (MC) and curcumin (CUR) is useful for the application of MC-CUR systems in food products. We used surface plasmon resonance (SPR) and ultraviolet-visible spectrophotometry (UV-vis) to study the complex formation between MC obtained from skimmed milk and CUR, MC carrying capacity, and thermal protection for CUR at a pH of 6.6. An MC could carry about 18,000 molecules of CUR. SPR suggested an enthalpy-driven process (∆H°â€¯= -64.63 kJ∙mol-1 and T∆S° ranging from -42.45 to -44.46 kJ∙mol-1). Temperature increased reduced the rate of MC-CUR complex formation and increased its dissociation rate. The activation energy for the formation of MC-CUR activated complexes was negative for association of free MC and CUR molecules (-62.8 kJ mol-1) and positive for dissociation of the thermodynamically stable complexes (1.80 kJ mol-1). MC protected the CUR against its thermal degradation when it was subjected to different temperatures (30, 40, 50, and 60 °C for 5.5 h). This study shows the importance of characterizing MC-small molecules interactions for better application of MC as a nanocarrier.

Novel magneto-responsive nanoplatforms based on MnFe2O4 nanoparticles layer-by-layer functionalized with chitosan and sodium alginate for magnetic controlled release of curcumin.

Remotely assisted drug delivery by means of magnetic biopolymeric nanoplatforms has been utilized as an important tool to improve the delivery/release of hydrophobic drugs and to address their low cargo capacity. In this work, MnFe2O4 magnetic nanoparticles (MNPs) were synthesized by thermal decomposition, coated with citrate and then functionalized with the layer-by-layer (LbL) assembly of polyelectrolyte multilayers, with chitosan as polycation and sodium alginate as polyanion. Simultaneous conductimetric and potentiometric titrations were employed to optimize the LbL deposition and to enhance the loading capacity of nanoplatforms for curcumin, a hydrophobic drug used in cancer treatment. ~200 nm sized biopolymer platforms with ~12 nm homogeneously embedded MNPs were obtained and characterized by means of XRD, HRTEM, DLS, TGA, FTIR, XPS and fluorescence spectroscopy techniques to access structural, morphological and surface properties, to probe biopolymer functionalization and to quantify drug-loading. Charge reversals (±30 mV) after each deposition confirmed polyelectrolyte adsorption and a stable LbL assembly. Magnetic interparticle interaction was reduced in the biopolymeric structure, hinting at an optimized performance in magnetic hyperthermia for magneto-assisted drug release applications. Curcumin was encapsulated, resulting in an enhanced payload (~100 µg/mg). Nanocytotoxicity assays showed that the biopolymer capping enhanced the biocompatibility of nanoplatforms, maintaining entrapped curcumin. Our results indicate the potential of synthesized nanoplatforms as an alternative way of remotely delivering/releasing curcumin for medical purposes, upon application of an alternating magnetic field, demonstrating improved efficiency and reduced toxicity.

Curcumin and fisetin internalization into Saccharomyces cerevisiae cells via osmoporation: impact of multiple osmotic treatments on the process efficiency.

Cell osmoporation is a simple and straightforward procedure of creating food-grade biocapsules. This study proposes a new protocol of sequential cell osmoporation stages and evaluates its impact on the efficiency of curcumin and fisetin internalization into Saccharomyces cerevisiae cells. To the best of our knowledge, this is the first report in the literature regarding the subject. To assess how multiple osmoporation stages influence the encapsulation efficiency (% EE), encapsulated amount of curcumin (IC) and fisetin (IF) into S. cerevisiae cells and cell viability, the residual supernatant was used for the subsequent encapsulation stages and viability was assessed by the CFU method. Quantification was carried through direct extraction, using an ultrasonic bath and UV-Vis spectrophotometry. Experimental data demonstrated that the addition of a second osmoporation stage increases both the EE (% EE) and the amount of encapsulated curcumin and fisetin (IC and IF). As a result, the EE was considerably improved and the obtained microcapsules contained a higher amount of the targeted bioactive compounds in its internal structure. However, adding a third osmoporation stage proved to less beneficial to the process efficiency due to its lower yield and the significant negative impact to cell viability. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time in the literature, a protocol of serial osmoporation stages to enhance the encapsulation efficiency of hydrophobic low molecular weight molecules (curcumin and fisetin) into Saccharomyces cerevisiae cells was determined. By increasing overall efficiency, this protocol empowers the encapsulation process and creates a rational way to reduce waste for future industrial osmoporation applications.

Cholesterol modulates curcumin partitioning and membrane effects.

Curcumin, a polyphenol molecule, presents a wide range of biological activities as antioxidant, anticancer, anti-inflammatory, antimicrobial and wound healing. Although some strengths attributed to curcumin derive from promiscuous biological activity, possibly because curcumin can interfere on many membrane located processes, knowledge of underlying interactions are lacking. Mammalian cell membranes characteristically contain 25 to 50% cholesterol/phospholipid ratio; however, most studies involving lipid bilayers and curcumin consider pure phosphatidylcholine and compare effects of curcumin on membranes with those of cholesterol. We investigated the interaction of curcumin with lipid bilayers containing cholesterol mimicking mammalian cells, and used spectroscopy techniques to determine partition coefficients, rigidity parameters and lytic activity. We found that curcumin partitions into different lipid bilayers (104 order coefficients that vary by less than a factor of two), containing cholesterol or not, and in the presence of sphingomyelin or phosphatidylserine. Curcumin decreases rigidity in all tested compositions, except that containing 40% cholesterol in which it increases the lipid packing order. In addition, curcumin induces leakage from giant unilamellar vesicles on a cholesterol concentration dependent way. Our results are compatible with the hypothesis of curcumin interaction with membranes being modulated by the liquid disordered phase and by the coexistence of liquid-ordered/liquid disordered phases. In bilayers containing cholesterol, curcumin assumes a more superficial location, drastically stiffens the 40% cholesterol bilayer and decreases the lytic effect. Our study may help researchers in the analysis of the biological effects of curcumin and curcumin-derived formulations by calling the attention to the discriminating role of the cholesterol content.

PAMAM-grafted TiO2 nanotubes as novel versatile materials for drug delivery applications.

PAMAM-grafted TiO2 nanotubes (PAMAM-TiO2NT) have been synthesized and evaluated as new drug nanocarriers, using curcumin (CUR), methotrexate (MTX), and silibinin (SIL) as model therapeutic compounds. TiO2NT were surface-modified using a silane coupling agent and subsequently conjugated with PAMAM dendrimer of the third generation. The characterization of PAMAM-TiO2NT nanomaterials was performed by FTIR, TEM, N2 adsorption-desorption isotherms, XRD, and TGA techniques, which accounted for a 2.6wt.% of PAMAM grafting in the prepared materials. The drug loading capacity, drug release properties, and cytotoxicity of PAMAM-TiO2NT showed a significant improvement compared to pristine TiO2NT, thus revealing the promising properties of these new materials for drug delivery purposes.

Renoprotective effect of the antioxidant curcumin: Recent findings.

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.