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Tartrazine (E102) is a controversial coloring agent whose potential impacts on human health are not fully understood. Our study reveals the vascular disrupting effects of tartrazine (TTZ) on developing zebrafish embryos in vivo and on human umbilical vein endothelial cells in vitro. The dye was shown to cause dose-dependent hemorrhages in zebrafish embryos. Analyzing transgenic zebrafish harboring fluorescent endothelial cells revealed that TTZ treatment disrupted cell organization into vessels in both the sub-intestinal vein and the brain area. Assays on human umbilical vein endothelial cells demonstrated that TTZ inhibited endothelial proliferation, tube formation, and migration in a dose-dependent manner. Taken together, our results indicate for the first time that TTZ can affect endothelial cell properties, possibly by disrupting Rho family GTPase pathways which control the cytoskeleton. Our finding provides a credible explanation for many reported human health impacts and offers prospective applications for biomedicine., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus, are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a natural food colorant, was examined for its antifungal effects against Aspergillus fumigatus via computational approach against the Ndk protein. Known and predicted interactions of Ndk with proteins was performed using the STRING application. Molecular docking was performed using Schrodinger Maestro software (V.14.1) under enhanced precision docking, with OPLS4 forcefield. MDS was performed for 500ns under OPLS4 forcefield and the TIP3P solvent system. The geometry optimization for DFT was performed using the Becke 3-parameter exchange functional (B3LYP) method. The Molecular Docking Studies revealed significant interactions with good binding energy between Violacein and Ndk. Subsequent MD Simulations confirmed the stability of Violacein-Ndk complex, compared to the reference ligand-complex, indicating a stable interaction between the protein and violacein. The energy band gap of violacein was found to be 0.072567 eV suggesting its softness with lower kinetic stability and higher chemical reactivity. The results suggest Violacein could potentially disrupt nucleotide metabolism by targeting Ndk, thus demonstrating antifungal activity. However, further experimental validation is required to confirm these computational findings and explore the practical use of Violacein in antifungal treatments., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Red pitaya fruit has become a source of natural colorant, because it is rich in betalains, a pigment that imparts a red-purple color that interests the food and cosmetics industries. This fruit also possesses high nutritional value, with a range of bioactive compounds known to confer potential health benefits and prevent chronic diseases, such as diabetes, which makes it useful for use as pharmaceutical agents and dietary supplements. In order to improve its technological and biological effects, a concentration will be required. Thus, the microfiltration, followed by vacuum concentration, can be an interesting strategy for this purpose. This study aimed to explore tangential microfiltration to produce microfiltered material, which is an important step to obtain the microfiltered red-purple pitaya concentrate. Therefore, physicochemical and chemical characterization (including 1 H NMR analysis) and biological properties (toxicity and diabetes) of this concentrate were assessed, using adult zebrafish as a model. The results show that microfiltration was carried out efficiently, with an average consumption of 95.75 ± 3.13 and 74.12 ± 3.58 kW h m -3 , varying according to the material used ("unpeeled pitaya pulp" or "pitaya pulp with peel," respectively). The in vivo tests indicated non-toxicity and hypoglycemic effect of the concentrate, since the blood glucose levels were significantly lower in the zebrafish groups treated with this concentrate in comparison with that of control group. Thus, this study suggests the potential of microfiltered red-purple pitaya concentrate as a promising multifunctional food-derived colorant, exhibiting beneficial biological effects far beyond its attractive color. PRACTICAL APPLICATION: Hylocereus polyrhizus (F.A.C. Weber) Britton & Rose has attracted attention as a potential source of natural colorants because of its red-purple skin and flesh color. In addition, this fruit has a range of bioactive compounds, which make it a valuable resource for providing potential health benefits and preventing chronic diseases such as diabetes. In this paper, the microfiltered red-purple pitaya concentrate showed beneficial biological effects far beyond its attractive color. Thus, this product can be considered a promising multifunctional food-derived colorant to use in the food, pharmaceutical, or cosmetics industries., (© 2024 Institute of Food Technologists.)

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.

Colors have been added to food naturally and artificially for centuries to make them look more appetizing. According to the Food and Drug Organization, eight artificial colors were registered for the nutrition application, one of them, is tartrazine, which is widely used in foods and cosmetics. Food colors significantly decrease weight and increase proteins, liver enzymes, thyroid hormones, total cholesterol, and triglyceride. Onion, as an antioxidant, can reduce the harmful effects of artificial food colors on weight gain, antioxidant activity, and blood biochemical factors. The present study aimed to evaluate the effects of the onion's antioxidant properties on serum biochemical factors and antioxidants in Wistar rats after consuming tartrazine. Eighty Rats were divided into four groups, 20 mice in each. The first group received water without additives and was considered the control, the second group received tartrazine, the third group received tartrazine with onion juice, and the fourth group received only onion juice through gastric gavage. This experiment was performed for 60 days, and then the antioxidant activities of superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GPx), and the biochemical parameters of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were measured. Tartrazine decreased the antioxidant activities of SOD, CAT, GPx, and the biochemical parameters of HDL and LDL. The results showed that the consumption of tartrazine causes the production of free radicals, which is the reason for the significant reduction of antioxidant activities and serum biochemical factors. Onion, as an antioxidant in this study, reduces the effects of tartrazine on antioxidant activities and serum biochemical factors., Competing Interests: The authors declare no conflict of interest.

Food colorants are commonly used as excipients in pharmaceutical and nutraceutical fields, but they have a wide range of other potential applications, for instance, as cytotoxic drugs or mediators of physical antimicrobial treatments. The photodynamic antibacterial activity of several edible food colorants is reported here, including E127, E129, E124, E122, E133, and E150a, alongside Rhein, a natural lipophilic antibacterial and anticancer compound found in medicinal plants. Minimal inhibitory concentration (MIC) values for S. aureus and E. coli showed that E127 and Rhein were effective against both bacteria, while other colorants exhibited low activity against E. coli . In some cases, dark pre-incubation of the colorants with Gram-positive S. aureus increased their photodynamic activity. Adding Rhein to E127 increased the photodynamic activity of the latter in a supportive mode. Optional sensing mechanism pathways of combined E127/Rhein action were suggested. The antibacterial activity of the studied colorants can be ranged as follows: E127/Rhein >> E127 >> E150a > E122 > E124 >> E129 ≈ E133. E127 was also found to exhibit photodynamic properties. Short ultrasonic treatment before illumination caused intensification of E127 photodynamic activity against E. coli when applied alone and especially in combination with Rhein. Food colorants exhibiting photo- and sonodynamic properties may have good potential in food preservation.

Color is the prime attribute with a large impact on consumers' perception, selection, and acceptance of foods. However, the belief in bio-safety protocols, health benefits, and the nutritional importance of food colors had focused the attention of the scientific community across the globe towards natural colorants that serve to replace their synthetic toxic counterparts. Moreover, multi-disciplinary applications of greener extraction techniques and their hyphenated counterparts for selective extraction of bioactive compounds is a hot topic focusing on process intensification, waste valorization, and retention of highly stable bioactive pigments from natural sources. In this article, we have reviewed available literature to provide all possible information on various aspects of natural colorants, including their sources, photochemistry and associated biological activities explored under in-vitro and in-vivo animal and human studies. However a particular focus is given on innovative technological approaches for the effective extraction of natural colors for nutraceutical and pharmaceutical applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A red pigment was prepared by reaction of chlorogenic acid (CGA) with tryptophan (TRP) in air at pH 9 (37% w/w yield) and evaluated as food dye. The main component of pigment was formulated as an unusual benzochromeno[2,3-b]indole linked to a TRP unit, featuring a cyanine type chromophore (λ max 542, 546 nm, 1% extinction coefficient of the sodium salt = 244 ± 2). The chromophore showed a minimal pH dependence and proved stable for at least 3 h at 90 °C, both at pH 3.6 or 7.0, whereas red wine anthocyanins showed a substantial (30%) and betanin a complete abatement after 1 h at the acidic pHs. An intense coloring of different food matrices was obtained with the pigment at 0.01 % w/w. No toxicity was observed up to 0.2 mg/mL on hepatic and colonic cell lines. These data make this dye a promising alternative for red coloring of food., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The drug transporter P-glycoprotein (P-gp) is often investigated in drug-interaction studies because the activity is modulated by a wide variety of xenobiotics including drugs, herbal products, and food components. In this study, we tested six common arylsulfonate food dyes-allura red, carmoisine, ponceau 4R, quinolone yellow, sunset yellow, and tartrazine-as activators and inhibitors of P-gp activity in vitro. The dyes were studied as P-gp activators by measuring ATPase activity in P-gp-expressing membranes. Compared to verapamil, a known activator of P-gp, the six food dyes showed no stimulatory activity. The potential for these six food dyes to act as P-gp inhibitors was tested in an intracellular efflux assay with P-gp-expressing cells. Compared to GF120918, a known P-gp inhibitor, there was no inhibitory activity for these six food dyes. The six food dyes tested do not interact with P-gp in vitro and, therefore, are unlikely cause clinical drug-food dye interactions. Further investigation is necessary to determine whether these food dyes could interact with other drug transporters., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Food coloring is often used as a coloring agent in foods, medicines and cosmetics, and it was reported to have certain carcinogenic and mutagenic effects in living organisms. Investigation of physiological parameters using zebrafish is a promising methodology to understand disease biology and drug toxicity for various drug discovery on humans. Zebrafish (Danio rerio) is a well-acknowledged model organism with combining assets such as body transparency, small size, low cost of cultivation, and high genetic homology with humans and is used as a specimen tool for the in-vivo throughput screening approach. In addition, recent advances in microfluidics show a promising alternative for zebrafish manipulation in terms of drug administration and extensive imaging capability. This pilot work highlighted the design and development of a microfluidic detection platform for zebrafish larvae through investigating the effects of food coloring on cardiovascular functionality and pectoral fin swing ability. The zebrafish embryos were exposed to the Cochineal Red and Brilliant Blue FCF pigment solution in a concentration of (0.02‰, 0.2‰) cultured in the laboratory from the embryo stage to hatching and development until 9 days post fertilization (d.p.f.). In addition, zebrafish swimming behaviors in terms of pectoral fin beating towards the toxicity screening were further studied by visualizing the induced flow field. It was evidenced that Cochineal Red pigment at a concentration of 0.2‰ not only significantly affected the zebrafish pectoral fin swing behavior, but also significantly increased the heart rate of juvenile fish. The higher concentration of Brilliant Blue FCF pigment (0.2%) increased heart rate during early embryonic stages of zebrafish. However, zebrafish exposed to food coloring did not show any significant changes in cardiac output. The applications of this proposed platform can be further extended towards observing the neurobiological/hydrodynamic behaviors of zebrafish larvae for practical applications in drug tests.

Today, Alzheimer's disease (AD) as the most prevalent type of dementia turns into one of the most severe health problems. Neurofibrillary tangle (NFT), mostly comprised of fibrils formed by Tau, is a hallmark of a class of neurodegenerative diseases. Tau protein promotes assembly and makes stable microtubules that play a role in the appropriate function of neurons. Polyanionic cofactors such as heparin, and azo dyes, can induce aggregation of tau protein in vitro. Sunset Yellow is a food colorant used widely in food industries. In the current work, we introduced degradation product (DP) of Sunset Yellow as an effective inducer of Tau aggregation. Two Tau aggregation inducers were produced, and then the aggregation kinetics and the structure of 1N4R Tau amyloid fibrils were characterized using ThT fluorescence spectroscopy, X-Ray Diffraction (XRD), circular dichroism (CD) and atomic force microscopy (AFM). Also, the toxic effects of the induced aggregates on RBCs and SH-SY5Y cells were demonstrated by hemolysis and LDH assays, respectively. Both inducers efficiently accelerated the formation of the amyloid fibril. Along with the confirmation of the β-sheets structure in Tau aggregates by Far-UV CD spectra, X-ray diffractions revealed the typical cross-β diffraction pattern. The oligomer formation in the presence of DPs was also confirmed by AFM. The possible in vivo effect of artificial azo dyes on Tau aggregation should be considered seriously as a newly opened dimension in food safety and human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study evaluates the photosensitizing effectiveness of sodium copper chlorophyllin, a natural green colorant commonly used as a food additive (E-141ii), to inactivate methicillin-sensitive and methicillin-resistant Staphylococcus aureus under red-light illumination. Antimicrobial photodynamic inactivation (aPDI) was tested on a methicillin-sensitive reference strain (ATCC 25923) and a methicillin-resistant Staphylococcus aureus strain (GenBank accession number Mh087437) isolated from a clinical sample. The photoinactivation efficacy was investigated by exposing the bacterial strains to different E-141ii concentrations (0.0, 1.0, 2.5, 5.0, 10.0, and 20.0 µM) and to red light (625 nm) at 30 J cm -2 . The results showed that E-141ii itself did not prevent bacterial growth for all tested concentrations when cultures were placed in the dark. By contrast, E-141ii photoinactivated both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) under red-light illumination. However, different dose responses were observed for MSSA and MRSA. Whilst the MSSA growth was inhibited to the detection limit of the method with E-141ii at 2.5 µM, >10 µM concentrations were required to inhibit the growth of MRSA. The data also suggest that E-141ii can produce reactive oxygen species (ROS) via Type I reaction by electron transfer from its first excited singlet state to oxygen molecules. Our findings demonstrate that the tested food colorant has great potential to be used in aPDI of MRSA.

The potential of passion fruit ( Passiflora edulis Sims) epicarp to produce anthocyanin-based colorants with bioactive properties was evaluated. First, a five-level three-factor factorial design coupled with response surface methodology was implemented to optimize the extraction of anthocyanins from dark purple epicarps. The extraction yield and cyanidin-3- O -glucoside content were used as response criteria. The constructed models were fitted to the experimental data and used to calculate the optimal processing conditions ( t = 38 min, T = 20 °C, S = 0% ethanol/water ( v/v ) acidified with citric acid to pH 3, and R S/L = 50 g/L) that lead to maximum responses (3.4 mg/g dried epicarp and 9 mg/g extract). Then, the antioxidant, antimicrobial, and cytotoxic activities of anthocyanin extracts obtained using the optimized method and a conventional extraction method were evaluated in vitro. The extract obtained by the optimized method revealed a higher bioactivity, in agreement with the higher cyanidin-3- O -glucoside content. This study highlighted the coloring and bioactive potential of a bio-based ingredient recycled from a bio-waste, which promotes a sustainable bioeconomy in the agri-food sector.

The most common cause of three major cardiovascular disorders, viz. ischemic heart disease (acute coronary syndrome), stroke and venous thromboembolism, is thrombosis. As blood platelets are considered the focal point of haemostasis, they play a key role in thrombosis and other cardiovascular diseases (CVDs). Various studies indicate that certain dietary components, such as phenolic compounds, selected vitamins (A and E) and unsaturated fatty acids, may act as important mediators in the prophylaxis and treatment of CVDs associated with platelet hyperactivation. It is possible that other components, such as natural and synthetic colourants may also possess such potential. Although studies have found individual food dyes or plant extracts acting as food colourants to demonstrate antiplatelet activity, no comprehensive and critical review has been performed of this activity. Therefore, the present paper reviews the current state of knowledge concerning the effect of colourants, especially natural ones, on blood platelet activity, as well as on thrombosis, being a consequence of platelet hyperactivation. It also discusses the molecular pathways of platelet activity as a basis for the development of effective antiplatelet therapies. The literature covered by this review suggests that such natural dyes can possess antiplatelet or anticoagulant activity; however, their antiplatelet action is complex and varies considerably, which may be attributed to differences in their chemical structure. Such natural food colourants may represent a promising alternative to synthetic food dyes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Erythrocytes exhibit high susceptibility to hemolysis in several pathologies due to the oxidation of cellular components. We hypothesized that annatto carotenoids improve the redox status of erythrocyte plasma membranes and promote a consequent increase in human erythrocyte resistance to hemolysis. The objective of this study was to evaluate whether food-grade annatto carotenoids can increase human erythrocyte resistance to hemolysis in vitro and ex vivo. For the in vitro experiment, erythrocytes from healthy volunteers were isolated and coincubated with bixin (BIX) or norbixin (NBIX) and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), glucose, or sodium nitrite (NaNO 2 ) as hemolysis inducers. In the ex vivo study, healthy volunteers consumed a capsule containing BIX or NBIX (0.05 mg/kg body weight per day) or placebo for 7 days before blood sample collection. Their erythrocytes were isolated and incubated with AAPH, glucose, or NaNO 2 . In both the ex vivo and in vitro studies, erythrocytes were subjected to osmotic fragility tests. The activity of antioxidant enzymes, and reduced glutathione and lipid peroxidation levels in erythrocytes were also evaluated ex vivo. In vitro BIX and NBIX not only reduced erythrocyte membrane fragility induced by AAPH, glucose, or NaNO 2 but also improved basal osmotic resistance in the micromole-per-liter range (P < .05). BIX and NBIX supplementation increased erythrocyte membrane resistance (P < .05), with BIX being more effective. Also, BIX and NBIX protected erythrocytes from lipid peroxidation and improved the cellular redox environment (P < .05). These results support the hypothesis that annatto carotenoids supplementation exerts antihemolytic properties by preventing the oxidative damage of human erythrocytes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sodium copper chlorophyllin (CHL) is a food colorant that exhibits many beneficial properties, including potential for use in radiotherapy. Nevertheless, genotoxicity studies investigating radioprotective properties against γ-radiation on human cells are rather scarce. The aim of this study was to assess the cytotoxicity, genotoxicity and induction of malondialdehyde formation on CHL pre-treated whole blood cells after an absorbed dose of 5 Gy γ-radiation. Irradiated whole blood cells pre-treated with 100, 500, and 1000 μg/mL CHL showed less DNA-strand breaks (10.92 ± 0.74%, 10.69 ± 0.68%, and 8.81 ± 0.69%, respectively) than untreated irradiated cells (12.58 ± 0.88%). At the same time, the level of malondialdehyde was lower in CHL pre-treated samples with 100, 500, and 1000 μg/mL CHL (14.11 ± 0.43, 16.35 ± 2.82, and 13.08 ± 1.03 μmol/L, respectively) compared to untreated irradiated samples (24.11 ± 0.25 μmol/L). Regarding cytotoxicity, no changes were observed in the samples tested. Another important finding is that CHL had no cyto/genotoxic properties toward human blood cells. Taken together, since CHL had no cyto/genotoxic effects and showed good radioprotective properties in human blood cells, further studies should be conducted in order to find its possible application in radiotherapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Demethoxycurcumin (DMC) is a safe and natural food-coloring additive, as well as an agent with several therapeutic properties. However, extensive glucuronidation in vivo has resulted in its poor bioavailability. In this study, we aimed to investigate the formation of DMC-O-glucuronides by uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) and its transport by breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in HeLa cells stably transfected with UGT1A1 (named HeLa1A1 cells). The chemical inhibitors Ko143 (a selective BCRP inhibitor) and MK571 (a pan-MRP inhibitor) both induced an obvious decrease in the excretion rate of DMC-O-glucuronides and a significant increase in intracellular DMC-O-glucuronide concentrations. Furthermore, BCRP knock-down resulted in a marked reduction in the level of excreted DMC-O-glucuronides (maximal 55.6%), whereas MRP1 and MRP4 silencing significantly decreased the levels of excreted DMC-O-glucuronides (a maximum of 42.9% for MRP1 and a maximum of 29.9% for MRP3), respectively. In contrast, neither the levels of excreted DMC-O-glucuronides nor the accumulation of DMC-O-glucuronides were significantly altered in the MRP4 knock-down HeLa cells. The BCRP, MRP1 and MRP3 transporters were identified as the most important contributors to the excretion of DMC-O-glucuronides. These results may significantly contribute to improving our understanding of mechanisms underlying the cellular disposition of DMC via UGT-mediated metabolism., Competing Interests: The authors have declared that no competing interests exist.

The human antimicrobial and immunomodulatory peptide LL-37 is ubiquitously expressed and secreted by epithelial cells of mucosal surfaces including the gastrointestinal tract, the primary absorption site of orally administered drugs and food components. Besides antimicrobial properties, LL-37 also contributes to the pathophysiology of various diseases such as ulcerative colitis, Crohn's disease and cancer. Non-covalent association of antiinflammatory drugs, porphyrin pigments, bile salts and food dyes to the peptide was uncovered and evaluated by circular dichroism (CD) spectroscopy. These agents induce the disorder-to-order conformational transition of the natively unstructured LL-37 leading to its helical folding. Even in the presence of chloride ions, when LL-37 is partially folded, the inducers were able to rise the α-helix content. CD titration data indicated positive cooperativity between the ligand molecules accommodated to the peptide chain resulting in multimeric complexes with apparent dissociation constants ranged from 2 to 500 μM. Computational docking suggested the prominent role of the Lys8-Arg19 segment in the accommodation of small molecules, governed principally by salt bridges and H-bonding. Since pleiotropic biological functions of LL-37 are strongly conformation-dependent, it could be anticipated that folding inducer compounds may modulate its in vivo actions and also of related cationic peptides., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The recovery of pepper phytochemicals present an interesting strategy in pursuit of new bioactive compounds and natural ingredients for agro-food, cosmetic and pharma industry uses, as replacements for the synthetic compounds and also in the valorisation of plant's by-products. Besides being used as a condiment, providing characteristic pungency, colour and flavour, the new pepper-derived ingredients could be used for the preservation and extension of industrial products' lifespan, as well as additives or technological ingredients with antioxidant and antimicrobial activities. Moreover, the application of the new products in pharmaceutical formulas for the treatment of inflammatory and pain-related conditions is also a possibility, since peppers contain capsaicinoids, carotenoids, phenolic compounds, vitamin C and A, and minerals, such as iron and calcium, which have a health-promoting potential. Further studies on appropriate extraction protocols, stability, safety and bioactivity are necessary to provide novel and promising pepper ingredients for food, cosmetic, and pharmaceutical applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A theoretical evaluation of the antioxidant property of a natural food colorant Peonidin has been performed. The most suitable mechanism for explaining the radical scavenging capacity of Peonidin is the Hydrogen Atom Transfer and the most active site for radical formation is position 3 and is confirmed through Mulliken charge analysis, pKa value evaluation, Bond Dissociation Energy values, and Natural Bond Orbital analysis. Position 3 and 5 in Peonidin exists in blood as deprotonated as their pKa values are lower than the pH of blood. Peonidin is highly reactive than Quercetin and less stable than flavan-3-ols due to the small band gap. Global descriptor analysis shows that PN prefers to accept electrons than to donate. The effect of number of OH groups and the nature of substituents are well explained through this work., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Curcumin (E100) is a natural colorant that, besides conferring color, has bioactivity, serving as an alternative to some artificial colorants. As a hydrophobic colorant, its modification/compatibilization with the aqueous medium is required to improve stability and enable its application in hydrophilic food matrices. Herein, different formulations of curcumin (curcumin powder: PC, water-dispersible curcumin: DC: and nanoencapsulated curcumin: NC) were evaluated as yogurt colorants. PC showed the strongest bioactivity in all assays (EC 50 values: 63 ± 2 to 7.9 ± 0.1 μg.mL -1 ; GI 50 values: 48 ± 1 to 17 ± 1 μg.mL -1 and MIC values: 0.0625 to 0.5 mg.mL -1 ), which might indicate that DC and NC reduce the short-term accessibility to curcumin. The tested curcumin formulations produced yogurts with different appearance, specifically associated with their color parameters, besides presenting slight changes in nutritional composition and free sugars and fatty acids profiles. The water compatible formulations (DC and NC) showed advantages over hydrophobic (PC) having a wider industrial utilization., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The aim of this work is to try to substitute some synthetic additives by a natural extract from red prickly pear (Opuntia stricta) which known by its richness on bioactive polysaccharides mainly consisting of galactose, rhamnose and galacturonic acid. This natural fruit has a high content of carbohydrates above 18.81% FM. It contains also a high level of polyphenols 152.25 ± 0.26 μg QE/mg PPE and flavonoids about 370.60 ± 0.12 μg GAE/mg of PPE. In addition, prickly pear extract (PPE) displayed a strong antioxidant and antimicrobial activities. These activities are likely due to its phenolic, flavonoid and carbohydrate contents. Moreover, the addition of 2.5% of PPE, as a natural colorant and antimicrobial agent in salami formulation, causes a decrease in hardness and chewiness of the formulated salami. Interestingly, PPE inhibited bacterial growth in salami stored at 4 °C over 30 days. Sensorial analysis shows that the color, taste and texture of salami prepared with 2.5% of PPE are markedly more appreciated by panelists. Our results suggest that the betalain pigment, carbohydrate and phenolic compounds present in PPE could be used as a natural colorant, antioxidant and antimicrobial agent without change of the sensory characteristics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sorghum (Sorghum bicolor) extract is traditionally used as red biocolorant in West Africa to colour foods, among which wagashi, a soft cheese. This biocolorant is a source of the phytoalexin apigeninidin and phenolic acids, and users claim that it has preservative effects next to its colouring properties. If such a claim can be scientifically substantiated, it adds a valuable functional property to this natural red colorant, thereby increasing its potential applications in the food industry. Hence, the present study evaluated the antimicrobial properties of dye sorghum extracts using challenge tests in broth and wagashi as a model of a popular food application. The alkaline extract and hot aqueous extract were used for dyeing wagashi by 87.7% and 12.3% of the traders, respectively. The dyeing procedure is perceived as a preservation strategy, and is also a means to maximise the revenues. However, results demonstrated that the application of sorghum biocolorant on wagashi had no inhibitory effect on the growth of fungi (Penicillium chrysogenum, Cladosporium macrocarpum) and Escherichia coli O157:H7. Furthermore, sorghum biocolorant in broth had no effect on growth of Listeria monocytogenes and Escherichia coli O157:H7. Consequently, the commonly used extracts for colouring soft West-African cheese did not show a preservative effect. In addition, dyeing did not affect the physico-chemical properties of wagashi. Still, the red colour hampered visual detection of microbial growth, thus clarifying the preservative effect reported by users.

Planarians have become widely recognized as one of the major animal models for regeneration studies in invertebrates. To induce RNA interference (RNAi) by feeding in planarians, the widely accepted protocol is one in which animals undergo two or three feedings of food containing double-stranded RNA (dsRNA) plus visible food coloring (e.g., blood) for confirmation of feeding by individual animals. However, one possible problem is that incorporated food coloring is often retained within the gut for several days, which makes it difficult to confirm the success of each round of dsRNA feeding based on the difference of the color density within the gut before and after feeding. As a consequence, the difference of appetite levels among individuals undergoing dsRNA feeding leads to phenotypic variability among them due to insufficient knockdown. In our attempts to overcome this problem, we have developed a novel method for achieving robust confirmation of the success of dsRNA feeding in individuals fed multiple times by means of including a combination of three different colored chalks (pink, yellow and blue) as food coloring. Notably, we found that this method is superior to the conventional method for positively marking individuals that actively consumed the dsRNA-containing food during four times of once-daily feeding. Using these selected animals, we obtained stable and sufficiently strong RNAi-induced phenotypes. We termed this improved multi-colored chalk-spiked method of feeding RNAi "Candi" and propose its benefits for gene function analysis in planarians., (© 2017 Japanese Society of Developmental Biologists.)

The chemical amaranth (AM) is permitted as a colouring agent in a variety of foods. Safety was established based on chronic rodent studies. AM and its metabolite naphthionic acid (NA) can be absorbed through the intestine, exposing circulating immune cells including splenocytes. An AM feeding study in rats demonstrated an increase in blood lymphocytes. Yet, in contrast, AM inhibited the delayed-type hypersensitivity reaction to antigen. DO11.10 mice express a T Cell Receptor specific for ovalbumin 323-339 peptide (OVAp) presented by I-A d MHCII. DO11.10 splenocytes were cultured to evaluate mechanisms by which AM and NA modulate immune cell function in vitro. Exposure to OVAp alone for 72 h induced cell proliferation, and combination with 2 or 20 μg/mL AM increased IFN-γ. Cytotoxicity was evident at higher concentrations of AM (200 and 2000 μg/mL) and NA (2000 μg/mL) in combination with OVAp, as both cell number and cytokine secretion decreased. At 200 μg/mL AM with OVAp, immunotoxicity gene expression was modified and OVAp-specific KJ1-26 + CD28 + cells became enriched. The equivalent dose of NA did not modify those parameters. Using an antigen-specific model in vitro, lower concentrations of AM potentiated pro-inflammatory cytokine production, and higher concentrations of AM and NA demonstrated cytotoxicity., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Previous research has shown that bleaching affects flavor and functionality of whey proteins. The role of different bleaching agents on vitamin and carotenoid degradation is unknown. The objective of this study was to determine the effects of bleaching whey with traditional annatto (norbixin) by hydrogen peroxide (HP), benzoyl peroxide (BP), or native lactoperoxidase (LP) on vitamin and carotenoid degradation in spray-dried whey protein concentrate 80% protein (WPC80). An alternative colorant was also evaluated. Cheddar whey colored with annatto (15 mL/454 L of milk) was manufactured, pasteurized, and fat separated and then assigned to bleaching treatments of 250 mg/kg HP, 50 mg/kg BP, or 20 mg/kg HP (LP system) at 50°C for 1 h. In addition to a control (whey with norbixin, whey from cheese milk with an alternative colorant (AltC) was evaluated. The control and AltC wheys were also heated to 50°C for 1 h. Wheys were concentrated to 80% protein by ultrafiltration and spray dried. The experiment was replicated in triplicate. Samples were taken after initial milk pasteurization, initial whey formation, after fat separation, after whey pasteurization, after bleaching, and after spray drying for vitamin and carotenoid analyses. Concentrations of retinol, a-tocopherol, water-soluble vitamins, norbixin, and other carotenoids were determined by HPLC, and volatile compounds were measured by gas chromatography-mass spectrometry. Sensory attributes of the rehydrated WPC80 were documented by a trained panel. After chemical or enzymatic bleaching, WPC80 displayed 7.0 to 33.3% reductions in retinol, β-carotene, ascorbic acid, thiamin, α-carotene, and α-tocopherol. The WPC80 bleached with BP contained significantly less of these compounds than the HP- or LP-bleached WPC80. Riboflavin, pantothenic acid, pyridoxine, nicotinic acid, and cobalamin concentrations in fluid whey were not affected by bleaching. Fat-soluble vitamins were reduced in all wheys by more than 90% following curd formation and fat separation. With the exception of cobalamin and ascorbic acid, water-soluble vitamins were reduced by less than 20% throughout processing. Norbixin destruction, volatile compound, and sensory results were consistent with previous studies on bleached WPC80. The WPC80 colored with AltC had a similar sensory profile, volatile compound profile, and vitamin concentration as the control WPC80., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Allura Red AC is an approved food color additive internationally with INS number 129, in the United States as food color subject to batch certification "Food, Drug, and Cosmetic" (FD&C) Red No. 40, and in Europe as food color additive with E number 129. In their evaluation of the color (2013), the European Food Safety Authority (EFSA) expressed concerns of potential genotoxicity, based primarily on one genotoxicity study that was not conducted according to Guidelines. The present in vivo genotoxicity study was conducted according to OECD Guidelines in response to EFSA's request for additional data. The animal species and strain, and the tissues examined were selected specifically to address the previously reported findings. The results show clear absence of genotoxic activity for Allura Red AC, in the bone marrow micronucleus assay and the Comet assay in the liver, stomach, and colon. These data addressed EFSA's concerns for genotoxicity. The Joint WHO/FAO Committee on Food Additives (JECFA) (2016) also reviewed the study and concluded that there is no genotoxicity concern for Allura Red AC. Negative findings in parallel genotoxicity studies on Tartrazine and Ponceau 4R (published separately) are consistent with lack of genotoxicity for azo dyes used as food colors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Tartrazine is approved as a food color additive internationally with INS number 102, in the United States as food color subject to batch certification "Food, Drug, and Cosmetic" (FD&C) Yellow No. 5, and in Europe as food color additive with E number 102. In their evaluation of the color (2013), the European Food Safety Authority (EFSA) expressed concerns of potential genotoxicity, based primarily on one genotoxicity study that was not conducted according to Guidelines. The present in vivo genotoxicity study was conducted according to OECD Guidelines in response to EFSA's request for additional data. The animal species and strain, and the tissues examined were selected specifically to address the previously reported findings. The results of this study show clear absence of genotoxic activity for Tartrazine, in the bone marrow micronucleus assay and the Comet assay in the liver, stomach, and colon. These data addressed EFSA's concerns for genotoxicity. The Joint WHO/FAO Committee on Food Additives (JECFA) (2016) also reviewed these data and concluded that there is no genotoxicity concern for Tartrazine. Negative findings in parallel genotoxicity studies on Allura Red AC and Ponceau 4R (published separately) are consistent with lack of genotoxicity for azo dyes used as food colors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Protein aggregation, a characteristic of several neurodegenerative diseases, displays vast conformational diversity from amorphous to amyloid-like aggregates. In this study, we have explored the interaction of tartrazine with myoglobin protein at two different pHs (7.4 and 2.0). We have utilized various spectroscopic techniques (turbidity, Rayleigh light scattering (RLS), intrinsic fluorescence, Congo Red and far-UV CD) along with microscopy techniques i.e. atomic force microscopy (AFM) and transmission electron microscopy (TEM) to characterize the tartrazine-induced aggregation in myoglobin. The results showed that higher concentrations of tartrazine (2.0-10.0mM) induced amorphous aggregation in myoglobin at pH 2.0 via electrostatic interactions. However, tartrazine was not able to induce aggregation in myoglobin at pH 7.4; because of strong electrostatic repulsion between myoglobin and tartrazine at this pH. The tartrazine-induced amorphous aggregation process is kinetically very fast, and aggregation occurred without the formation of a nucleus. These results proposed that the electrostatic interaction is responsible for tartrazine-induced amorphous aggregation. This study may help in the understanding of mechanistic insight of aggregation by tartrazine., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Interaction of two food colorant dyes, amaranth and tartrazine, with lysozyme was studied employing multiple biophysical techniques. The dyes exhibited hypochromic changes in the presence of lysozyme. The intrinsic fluorescence of lysozyme was quenched by both dyes; amaranth was a more efficient quencher than tartrazine. The equilibrium constant of amaranth was higher than that of tartarzine. From FRET analysis, the binding distances for amaranth and tartrazine were calculated to be 4.51 and 3.93 nm, respectively. The binding was found to be dominated by non-polyelectrolytic forces. Both dyes induced alterations in the microenvironment surrounding the tryptophan and tyrosine residues of the protein, with the alterations being comparatively higher for the tryptophans than the tyrosines. The interaction caused significant loss in the helicity of lysozyme, the change being higher with amaranth. The binding of both dyes was exothermic. The binding of amaranth was enthalpy driven, while that of tartrazine was predominantly entropy driven. Amaranth delayed lysozyme fibrillation at 25 μM, while tartrazine had no effect even at 100 μM. Nevertheless, both dyes had a significant inhibitory effect on fibrillogenesis. The present study explores the potential antiamyloidogenic property of these azo dyes used as food colorants.

Betalains are important pigments for the food, pharmaceutical, and cosmetics industry. In the yellow Stenocereus pruinosus fruits (pitayas), total betalain concentration, Folin-Ciocalteu reduction capacity, and antiradical capacity per dry weight were 2345.9μgg -1 , 7.3mg gallic acid equivalentsg -1 , and 48.8μmol Trolox equivalentg -1 , respectively. The stability of betaxanthins, which represent 89% of total betalains in yellow pitayas, was evaluated over a range of pH, temperature, as well as in the presence of food additives. Maximum stability was observed at pH6.6, and addition of ascorbic acid increased the half-life 1.8 times. Thermal stability at pH6.48±0.05 was also evaluated from 50°C to 80°C, over which the activation energy for betaxanthin degradation was determined to be 66.2kJmol -1 . Model gelatin gummies and beverages were then prepared with pitaya juice or pulp, and pigment retention and color parameters were investigated during storage under various conditions. To match the yellow color of commercial products, gummies were supplemented with 4.6% w/w juice or pulp, and beverages were supplemented with 5% w/v juice, achieving H° values of 69.0-86.2° and 64.6-87.1°, respectively. Results indicate that betaxanthins were more stable in gummies than in beverages, and that pigment retention increased when products were stored in the dark or at low temperatures. Also, different changes in color during storage were observed between gummies and beverages., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Allura red is a widely used food colorant, but there is debate on its potential security risk. In the present study, we found that degradation products of the dye were more potent agents with higher carbonic anhydrase inhibitory action than the parent dye. The mechanism by which the compounds inhibit the enzyme activity has been determined as competitive mode. In addition, the enzyme binding properties of the compounds were investigated employing different spectroscopic techniques and molecular docking. The analyses of fluorescence quenching data revealed the existence of the same binding site for the compounds on the enzyme molecule. The thermodynamic parameters of ligand binding were not similar, which indicates that different interactions are responsible in binding of the parent dye and degradation products to the enzyme. It appears that enzyme inhibition should be considered, more seriously, as a new opened dimension in food safety., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

It has been reported that some of the food additives may cause sensitization, inflammation of tissues, and potentially risk factors in the development of several chronic diseases. Thus, we hypothesized that expressions of common inflammatory molecules - known to be involved in the development of various inflammatory conditions and cancers - are affected by these food additives. We investigated the effects of commonly used food preservatives and artificial food colorants based on the expressions of NFκB, GADD45α, and MAPK8 (JNK1) from the tissues of liver. RNA was isolated based on Trizol protocol and the activation levels were compared between the treated and the control groups. Tartrazine alone could elicit effects on the expressions of NFκB (p = 0.013) and MAPK8 (p = 0.022). Azorubine also resulted in apoptosis according to MAPK8 expression (p = 0.009). Preservatives were anti-apoptotic in high dose. Sodium benzoate (from low to high doses) dose-dependently silenced MAPK8 expression (p = 0.004 to p = 0.002). Addition of the two preservatives together elicited significantly greater expression of MAPK8 at half-fold dose (p = 0.002) and at fivefold dose (p = 0.008). This study suggests that some of the food preservatives and colorants can contribute to the activation of inflammatory pathways.

Flesh of Basella alba L. mature fruits bearing deep-violet juice provides a novel and potential source of natural colorant. To minimize the pigment purification process and warrant safety acceptability, B. alba colorant powder (BACP) was prepared using mature fruits through a practical batch preparation and subjected to fundamental pigment characterization, food safety assessment and bio-function evaluation. Yield of the dehydrated B. alba colorant powder (BACP) was 37 g/kg fresh fruits. Reconstituted aqueous solution of the BACP exhibited an identical visible spectrum (400-700 nm) as that of fresh juice. Color of the solution (absorbance at 540 nm) was stable in a broad pH ranged from 3 to 8 and enhanced by co-presence of calcium and magnesium ions, while was rapidly bleached by ferrous and ferric ions. For in vivo food safety evaluation, ICR mice were daily gavage administered with BACP up to 1000 mg/kg body weight for 28 days. Organ weight determination, serum biochemical analysis and histopathological examination of hearts, livers, lungs and kidneys revealed no obvious health hazard. In vitro anti-inflammatory activity of BACP was characterized in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. BACP exerted potent anti-inflammatory activity by down-regulation of inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α, IL-1β, IL-6 and IL-12 and the blockage of IκB kinase (IKK)/IκB/nuclear factor-κ B (NFκB) activation cascade. These results supported that BACP may serve as a beneficial alternative of natural food colorant.

Interaction of the food colorant acid red 27 with double stranded DNA was investigated using spectroscopic and calorimetric methods. Absorbance and fluorescence studies suggested an intimate binding interaction between the dye and DNA. The quantum efficiency value testified an effective energy transfer from the DNA base pairs to the dye molecules. Minor groove displacement assay with Hoechst 33258 revealed that the binding occurs in the minor groove of DNA. Circular dichroism studies revealed that acid red 27 induces moderate conformational perturbations in DNA. Results of calorimetric studies suggested that the complexation process was driven largely by positive entropic contribution with a smaller favorable enthalpy contribution. The equilibrium constant of the binding was calculated to be (3.04 ± 0.09) × 10(4)  M(-1) at 298.15 K. Negative heat capacity value along with the enthalpy-entropy compensation phenomenon established the involvement of dominant hydrophobic forces in the binding process. Differential scanning calorimetry studies presented evidence for an increased thermal stability of DNA on binding of acid red 27. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Caramel color is widely used in the food industry, and its many variations are generally considered to be safe. It has been known for a long time that THI (2-acetyl-4-(tetrahydroxybutyl)imidazole), a component of caramel color III, causes lymphopenia in animals through sphingosine 1-phosphate (S1P) lyase (S1PL) inhibition. However, this mechanism of action has not been fully validated because THI does not inhibit S1PL in vitro. To reconcile this situation, we examined molecular details of THI mechanism of action using "smaller" THI derivatives. We identified a bioactive derivative, A6770, which has the same lymphopenic effect as THI via S1PL inhibition. In the case of A6770 we observe this effect both in vitro and in vivo, and demonstrate that A6770 is phosphorylated and inhibits S1PL in the same way as 4-deoxypyridoxine. In addition, A6770 was detected in rat plasma following oral administration of THI, suggesting that A6770 is a key metabolic intermediate of THI., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chestnut shell melanin can be used as a colorant and antioxidant, and fractionated into three fractions (Fr. 1, Fr. 2, and Fr. 3) with different physicochemical properties. Antioxidant activities of the fractions were comparatively evaluated for the first time. The fractions exhibited different antioxidative potential in different evaluation systems. Fr. 1, which is only soluble in alkaline water, had the strongest peroxidation inhibition and superoxide anion scavenging activity; Fr. 2, which is soluble in alkaline water and hydrophilic organic solvents but insoluble in neutral and acidic water, had the greatest power to chelate ferrous ions; and Fr. 3, which is soluble both in hydrophilic organic solvents and in water at any pH conditions, had the greatest hydroxyl (·OH) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH·) radicals scavenging abilities, reducing power, and phenolic content. The pigment fractions were superior to butylated hydroxytolune (BHT) in ·OH and DPPH· scavenging and to ethylene diamine tetraacetic acid (EDTA) in the Fe(2+)-chelation. They were inferior to BHT in peroxidation inhibition and O₂·(-) scavenging and reducing power. However, BHT is a synthetic antioxidant and cannot play the colorant role. The melanin fractions might be used as effective biological antioxidant colorants.

2-Acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI) is observed as a minor contaminant in caramel food colourings (E 150c). Feeding experiments with rodents have revealed a significant lymphopenic effect that has been linked to the presence of THI in these food colourings. Pyridoxal kinase inhibition by THI has been suggested, but not demonstrated, as a mode of action as it leads to lowered levels of pyridoxal-5'-phosphate, which are known to cause lymphopenia. Recently, THI was also shown to inhibit sphingosine-1-phosphate lyase causing comparable immunosuppressive effects and derivatives of THI are being developed for the treatment of rheumatoid arthritis in humans. Interestingly, sphingosine-1-phosphate lyase activity depends on pyridoxal-5'-phosphate, which in turn is provided by pyridoxal kinase. This report shows that THI does inhibit pyridoxal kinase with competitive and mixed-type non-competitive behaviour towards its two substrates, pyridoxal and ATP, respectively. The corresponding inhibition constants are in the low millimolar range.

Background: Anthocyanins and other polyphenols from flowers and bracts of Thymus sp. are studied. An anthocyanin-rich food colourant with interesting high antioxidant activity from Thymus moroderi has been obtained, and applied to colour foods., Results: Anthocyanins and other polyphenols from T. moroderi and another five Thymus sp. were extracted in methanol/hydrochloric acid 0.1 mol L(-1) (50/50, v/v) 2 h stirring at 50 °C. They were identified and quantified by HPLC-PDA-MS and UHPLC-PDA-fluorescence, as total individual polyphenols. Total polyphenols were also determined. Flowers had higher anthocyanins and other polyphenols concentrations than bracts; for example, total polyphenols content of T. moroderi were 131.58 and 61.98 g GAE kg(-1) vegetal tissue, respectively. A liquid concentrated colourant was obtained from T. moroderi using water/citric acid as solvent. It was characterised and compared with other two commercial anthocyanin-rich food colourants from red grape skin and red carrot (colour strength of 1.7 and 3.6 AU, respectively). T. moroderi colourant had 1.2 AU colour strength, and high storage stability (>97.1% remaining colour after 110 days at 4 °C). It showed a higher polyphenols content than commercial colourants. Its antioxidant activity was 0.707 mmol Trolox eq. g(-1) plant dry weight, 69.5 times higher than red carrot. The three colourants were applied to colour yogurts, giving pinky tonalities. The colour did not change evidently (ΔE*(ab)  < 3) when stored under refrigeration during 1 month., Conclusions: T. moroderi can be a source of anthocyanin-rich food colourant (E-163) with both high polyphenols content and high antioxidant activity. This colourant gives a stable colour to a yogurt during 1 month. These results expand the use of natural colourants., (© 2014 Society of Chemical Industry.)

The aim of this study was to investigate the phenolic composition of a natural food colourant (G8000™) as well as its effects on plasma markers after 28-day consumption by healthy individuals at a dietary dose (70 g). Parameters of total cholesterol and its fractions, triglycerides and plasma enzymes biomarkers of muscle injury were measured. Major compounds identified in G8000™ by ESI-MS showed the presence of anthocyanins, organic acids, phenolic acids as well as monosaccharides. HDL levels significantly increased from 43 ± 10.2 mg/dL to 95 ± 16.9 mg/dL. LDL levels significantly decreased from 110 ± 40.9 mg/dL to 69 ± 39 mg/dL (p < 0.001). No significant statistical differences (p > 0.05) were observed for total cholesterol, triglycerides and VLDL. After the intake, plasma enzyme CK-MB decreased from 20 ± 12.1 U/L to 10 ± 1.9 U/L while LDH levels increased from 275 ± 124.4 U/L to 317 ± 114.7 U/L (p < 0.005). No significant differences were observed for CK levels. Taken together, dietary intake of natural colourant G8000™ was able to exert beneficial effects on atherosclerosis biomarkers.

The use of anthocyanins in food products as colorants has been limited because of their instability toward alkaline pH and high temperature. This study aimed to determine color stability and mutagenicity of the anthocyanin-based pigment extract from bulb cultures of Hippeastrum (Hippeastrum reticulatum). The pigment extract retained its reddish-orange color under alkaline conditions (⩽pH 11) and was stable up to 6 h at 95 °C. The mutagenicity of the extract was evaluated in vitro and in vivo. Hippeastrum pigment extract up to 1.25 mg plate(-1) was found non-mutagenic in Ames test using Salmonella typhimurium strain TA98 and TA100. Chromosome aberrations were observed when human lymphocytes were treated with the extract up to 1.5 mg ml(-1). However, the extract up to 1.4 mg ml(-1) was found to exhibit relatively low or no mutagenicity in in vitro comet assays with human lymphocytes. In in vivo micronucleated reticulocyte assay, mice were treated orally with the extract up to 1 g kg(-1). No significant increase of the percentage of micronucleated peripheral reticulocytes compared to the negative control groups was found. Taken together, our study indicates that Hippeastrum pigment extract is potentially applicable as an additive colorant in the diet and related products., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Bulk- and nano-scale titanium dioxide (TiO2) has found use in human food products for controlling color, texture, and moisture. Once ingested, and because of their small size, nano-scale TiO2 can interact with a number of epithelia that line the human gastrointestinal tract. One such epithelium responsible for nutrient absorption is the small intestine, whose constituent cells contain microvilli to increase the total surface area of the gut. Using a combination of scanning and transmission electron microscopy it was found that food grade TiO2 (E171 food additive coded) included ∼25% of the TiO2 as nanoparticles (NPs; <100 nm), and disrupted the normal organization of the microvilli as a consequence of TiO2 sedimentation. It was found that TiO2 isolated from the candy coating of chewing gum and a commercially available TiO2 food grade additive samples were of the anatase crystal structure. Exposure to food grade TiO2 additives, containing nanoparticles, at the lowest concentration tested within this experimental paradigm to date at 350 ng/mL (i.e., 100 ng/cm(2) cell surface area) resulted in disruption of the brush border. Through the use of two independent techniques to remove the effects of gravity, and subsequent TiO2 sedimentation, it was found that disruption of the microvilli was independent of sedimentation. These data indicate that food grade TiO2 exposure resulted in the loss of microvilli from the Caco-2BBe1 cell system due to a biological response, and not simply a physical artifact of in vitro exposure.

The aim of this study was to investigate the possible influence of halogenated compounds on thyroid hormone metabolism via inhibition of iodotyrosine deiodinase (IYD) activity. The structure-activity relationships of 44 halogenated compounds for IYD-inhibitory activity were examined in vitro using microsomes of HEK-293 T cells expressing recombinant human IYD. The compounds examined were 17 polychlorinated biphenyls (PCBs), 15 polybrominated diphenyl ethers (PBDEs), two agrichemicals, five antiparasitics, two pharmaceuticals and three food colorants. Among them, 25 halogenated phenolic compounds inhibited IYD activity at the concentration of 1×10(-4)M or 6×10(-4)M. Rose bengal was the most potent inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4'-hydroxy-2,2',4-tribromodiphenyl ether, 4-hydroxy-2,3',3,4'-tetrabromodiphenyl ether, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl, 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether, triclosan, and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. However, among PCBs and PBDEs without a hydroxyl group, including their methoxylated metabolites, none inhibited IYD activity. These results suggest that halogenated compounds may disturb thyroid hormone homeostasis via inhibition of IYD, and that the structural requirements for IYD-inhibitory activity include halogen atom and hydroxyl group substitution on a phenyl ring., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Preoperative cleansing of a patient's skin with chlorhexidine gluconate (CHG) in alcohol is superior to cleansing with povidone-iodine for preventing surgical site infection (SSI) after clean-contaminated surgery (Darouilche et al 2010). However, 2% CHG in 70% alcohol, tinted pink, is colourless when applied to limbs for surgery and complete coverage cannot be assured. The purpose of the study was to evaluate the efficacy of food colouring added to CHG in preoperative skin preparation. Two hundred and eight subjects were randomly selected from a population of healthy young adults and were given a questionnaire. They were excluded if they had a known allergy to CHG or food dye, a current infection at the preparation site, or previous preparation with CHG at the site. CHG with food dye additive was applied on the subject's left foot while CHD without the additive was applied on the right. Skin swabs were then taken of both feet and plated on blood agar plates and incubated for 48 hours. Assessment of growth was compared. Patients treated with tinted CHG had around 3.4 times (95% CI: 1.5, 7.8) the risk of a positive bacterial swab compared with those treated with untinted CHG. The efficacy of CHG significantly decreased with food colouring additive. This is consistent with previous studies conducted on similar incompatible substances. In order to have the full efficacy of CHG as a preparation, much thought and care needs to be taken to prevent contamination of the site and substance.

Objectives: To test the individual effect of artificial food colorings (AFCs) and a preservative on the behavior of the general Chinese population., Method: One hundred thirty children (70 boys and 60 girls) in Hong Kong with a mean age of 8.64 years were enlisted to the study with a within-subject crossover between AFCs, a preservative (sodium benzoate), and a placebo capsule. Two behavior scores were used including the strengths and weaknesses of attention deficit hyperactivity disorder and normal behavior rating scale and the child behavior checklist-teacher report form., Results: Capsule A containing AFCs and Capsule B containing sodium benzoate had no significant adverse effect compared with placebo in both behavior scores. This result persisted when analysis was restricted to children with 85% consumption of capsule (per protocol analysis)., Conclusion: There seem to be no significant associations between AFCs and a preservative on Chinese children's behavior at the age of 8 to 9 years. Future directions and implications of this research are discussed.

Prodigiosin (PG) has been reported to have various biological activities. With the aim of increasing Serratia marcescens TKU011 PG production on squid pen powder (SPP)-containing medium, the effects of phosphate and ferrous ion supplementation, autoclave treatment, and aeration were studied. Autoclave treatment showed positive results for PG productivity (2.48 mg/mL), which increased 2.5-fold when the organism was incubated in 50 mL of 40-min autoclaved medium in a baffle-based flask (250 mL) containing 1.5% SPP at 30 °C for 1 day and then at 25 °C for 2 additional days. Furthermore, the use of pigments including PG and the food colorants Allura Red AC (R40) and Tartrazine (Y4) as insecticides was also investigated. The lethal concentrations causing 50% Drosophila larval mortality (LC50) of PG, Y4, and R40 using a 5-d exposure period were 230, 449, and 30000 ppm, respectively. The results indicated that the biopigment PG and the food colorant Y4 were potentially toxic to Drosophila larvae., (© 2013 Institute of Food Technologists®)

Tocotrienols (T3), the lesser known isomers of vitamin E, have been reported to possess anticancer activity both in in vitro and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of dietary supplementation with annatto-T3 (90% δ-T3 and 10% γ-T3) on the spontaneous development of mammary tumors in HER-2/neu transgenic mice. Underlying mechanisms of the antitumor effect were evaluated by studying apoptosis, senescent-like growth arrest, immune modulation, oxidative effect and the expression of HER-2/neu in tumoral mammary glands of transgenic mice and in vitro in human and mice tumor cell lines. Annatto-T3 supplementation delayed the development of mammary tumors, reducing the number and size of mammary tumor masses and those of lung metastases. In annatto-T3-supplemented mice, both apoptosis and senescent-like growth arrest of tumor cells were increased in mammary glands while no immune modulation was observed. In vitro, a dose-dependent inhibition of cell growth, increased apoptosis and senescent-like growth arrest and a time-dependent accumulation of reactive oxygen species were observed in tumor cells treated with annatto-T3 or purified δ-T3. Annatto-T3 reduced both HER-2/neu mRNA and p185(HER-2/neu) protein in tumors and in tumor cell lines. The results show that the antitumor effect of annatto-T3 supplementation in HER-2/neu transgenic mice is mainly related to the direct induction of oxidative stress, senescent-like growth arrest and apoptosis of tumor cells rather than to an immune modulation.

The food dye FD&C Blue No. 1 (Brilliant Blue FCF [BB FCF]) is structurally similar to the purinergic receptor antagonist Brilliant Blue G (BBG), which is a well-known inhibitor of the ionotropic P2X7 receptor (P2X7R). The P2X7R functionally interacts with the membrane channel protein pannexin 1 (Panx1) in inflammasome signaling. Intriguingly, ligands to the P2X7R, regardless of whether they are acting as agonists or antagonists at the receptor, inhibit Panx1 channels. Thus, because both P2X7R and Panx1 are inhibited by BBG, the diagnostic value of the drug is limited. Here, we show that the food dye BB FCF is a selective inhibitor of Panx1 channels, with an IC50 of 0.27 µM. No significant effect was observed with concentrations as high as 100 µM of BB FCF on P2X7R. Differing by just one hydroxyl group from BB FCF, the food dye FD&C Green No. 3 exhibited similar selective inhibition of Panx1 channels. A reverse selectivity was observed for the P2X7R antagonist, oxidized ATP, which in contrast to other P2X7R antagonists had no significant inhibitory effect on Panx1 channels. Based on its selective action, BB FCF can be added to the repertoire of drugs to study the physiology of Panx1 channels. Furthermore, because Panx1 channels appear to be involved directly or indirectly through P2X7Rs in several disorders, BB FCF and derivatives of this "safe" food dye should be given serious consideration for pharmacological intervention of conditions such as acute Crohn's disease, stroke, and injuries to the central nervous system.

Purple corn color is a widely used food colorant that was reported to have attenuating effects on hypertension, diabetes, and to have anti-cancer effects on colon and breast cancer. Our study is the first on its possible chemoprevention effects against prostate cancer. For this purpose an androgen-dependent prostate cancer cell line, LNCaP, was used to examine effects in vitro. Purple corn color inhibited the proliferation of LNCaP cells by decreasing the expression of Cyclin D1 and inhibiting the G1 stage of the cell cycle. Thirty-six male transgenic rats for adenocarcinoma of prostate were fed basic diet or diet with purple corn color for 8 weeks. Purple corn color decreased the incidence of adenocarcinoma in the lateral prostate and slowed down the progression of prostate cancer. A lower Ki67 positive rate, a decrease of the expression of Cyclin D1, and downregulation of the activation of Erk1/2 and p38 MAPK were observed in the group consuming purple corn color in the diet. Since purple corn color is a mixture, determining its active component should help in the understanding and usage of purple corn color for prostate cancer chemoprevention. Therefore, the three major anthocyanins in purple corn color, cyanidin-3-glucoside, pelargonidin-3-glucoside and peonidin-3-glucoside, were tested with LNCaP cells. The results suggested that cyanidin-3-glucoside and pelargonidin-3-glucoside are the active compounds., (© 2012 Japanese Cancer Association.)

The genus Monascus, comprising nine species, can reproduce either vegetatively with filaments and conidia or sexually by the formation of ascospores. The most well-known species of genus Monascus, namely, M. purpureus, M. ruber and M. pilosus, are often used for rice fermentation to produce red yeast rice, a special product used either for food coloring or as a food supplement with positive effects on human health. The colored appearance (red, orange or yellow) of Monascus-fermented substrates is produced by a mixture of oligoketide pigments that are synthesized by a combination of polyketide and fatty acid synthases. The major pigments consist of pairs of yellow (ankaflavin and monascin), orange (rubropunctatin and monascorubrin) and red (rubropunctamine and monascorubramine) compounds; however, more than 20 other colored products have recently been isolated from fermented rice or culture media. In addition to pigments, a group of monacolin substances and the mycotoxin citrinin can be produced by Monascus. Various non-specific biological activities (antimicrobial, antitumor, immunomodulative and others) of these pigmented compounds are, at least partly, ascribed to their reaction with amino group-containing compounds, i.e. amino acids, proteins or nucleic acids. Monacolins, in the form of β-hydroxy acids, inhibit hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis in animals and humans.