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1.
J Pharm Biomed Anal ; 177: 112878, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31561062

RESUMO

Trans-crocin 4 (TC4) is an important carotenoid constituent of saffron showing potential activity against Alzheimer's Disease (AD) due to its antioxidant and antiamyloidogenic properties. Metabolomics is an emerging scientific field that enhances biomarker discovery and reveals underlying biochemical mechanisms aiming towards the early subclinical diagnosis of diseases. To date, there are no reports on the changes induced to mice plasma metabolome after TC4 administration. We report a novel untargeted UHPLC-ESI HRMS metabolomics strategy to determine the alteration of the metabolic fingerprint following i.p. administration of TC4 in male and female mice. Blood samples from fiftysix mice treated with TC4 as well as from control animals were analyzed with UHPLC-ESI HRMS. Statistical evaluation of the results was achieved by multivariate analysis (MVA), i.e., principal component analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA) in order to discover the variables that contributed to the discrimination between treated and untreated groups which were identified by online database searching (e.g., Metlin, HMDB, KEGG) aided by chemometric processing, e.g., covariance searching etc. Due to the high variability imposed by various factors, e.g., sex of the animals participating in the study, administration dose and time-points of sacrifice, multilevel sparse PLS-DA analysis, e.g., splitting variation to each individual component, has been employed as a more efficient approach for such designs. This methodology allowed the identification of the time sequence of metabolome changes due to the administration of TC4, whereas a sex-related effect on the metabolome is indicated, denoting that the administration in both sexes is indispensable in order to acquire safe conclusions as reliable metabolome pictures. The results demonstrated a number of annotated metabolites playing a potential role in neuroprotection while they are closely related to AD. Moreover, five additional annotated metabolites were involved in the steroid biosynthesis pathway while two of them may be considered as putative neuroprotective agents.


Assuntos
Carotenoides/farmacocinética , Crocus/química , Metabolômica/métodos , Fármacos Neuroprotetores/farmacocinética , Animais , Vias Biossintéticas/efeitos dos fármacos , Carotenoides/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Injeções Intraperitoneais , Masculino , Espectrometria de Massas/métodos , Camundongos , Modelos Animais , Fármacos Neuroprotetores/administração & dosagem , Fatores Sexuais , Esteroides/biossíntese
2.
Food Chem ; 300: 125232, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352286

RESUMO

The mechanisms of main tomato carotenes (phytoene, phytofluene, lycopene and ß-carotene) intestinal absorption are still only partly understood. We thus compared carotene bioavailability in mice after gavage with carotene-rich oil-in-water emulsions. We also determined each carotene absorption profile along the duodenal-ileal axis of the intestine to identify their respective absorption sites and compared these profiles with the gene expression sites of their identified transporters, i.e. SR-BI and CD36. Our data show that phytofluene presented a significantly higher bioavailability compared to lycopene and ß-carotene (areas under the curve of 0.76 ±â€¯0.09 vs. 0.30 ±â€¯0.05, 0.09 ±â€¯0.05 and 0.08 ±â€¯0.01 µmol/L·h for phytofluene, phytoene, lycopene and ß-carotene, respectively). ß-Carotene was mostly converted in the proximal and median intestine. Phytoene and phytofluene accumulation tended to be more important in the distal intestine, which did not correlate with the proximal expression of both Scarb1 and CD36. Overall, these results highlight the high bioavailability of phytofluene.


Assuntos
Carotenoides/farmacocinética , Absorção Intestinal , Licopeno/farmacocinética , beta Caroteno/farmacocinética , Animais , Disponibilidade Biológica , Antígenos CD36/genética , Intestinos/efeitos dos fármacos , Lycopersicon esculentum/química , Masculino , Camundongos Endogâmicos C57BL , Período Pós-Prandial , Receptores Depuradores Classe B/genética
3.
Food Chem ; 298: 125040, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31261008

RESUMO

The effects of co-digestion of red cabbage with carrot, baby spinach and/or cherry tomato on the bioaccessibility of anthocyanins and carotenoids such as α-carotene, ß-carotene, lutein and lycopene were examined using a simulated in vitro gastro-intestinal digestion model. The individual vegetables and their mixtures were digested with and without added a standardised salad dressing. Bioaccessibility of total anthocyanins was enhanced by 10-15% (p < 0.05) when red cabbage was co-digested with the carotenoid-rich vegetables, except with carrot. In contrast, the co-digestion of red cabbage with carrot decreased bioaccessibility of total carotenoids by 21-33% (p < 0.05), and with cherry tomato by 42-56% (p < 0.05). The bioaccessibility of a given carotenoid varied depending on the vegetable matrix. Among the tested vegetable mixtures, red cabbage and baby spinach when co-digested demonstrated that anthocyanins and carotenoids were equally bioaccessible (total anthocyanin bioaccessibility of 62-66% and total carotenoid bioaccessibility of 66%).


Assuntos
Antocianinas/farmacocinética , Brassica/química , Carotenoides/farmacocinética , Lycopersicon esculentum/química , Verduras/química , Disponibilidade Biológica , Brassica/metabolismo , Daucus carota/química , Digestão , Humanos , Lycopersicon esculentum/metabolismo , Saliva , Spinacia oleracea/química , Verduras/metabolismo
4.
Food Chem Toxicol ; 130: 44-60, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100302

RESUMO

Natural products with high pharmacological potential and low toxicity have been considered as the novel therapeutic agents. Crocetin is an active constituent of saffron (Crocus sativus L.) stigma, which in its free-acid form is insoluble in water and most organic solvents. Crocetin exhibits various health-promoting properties including anti-tumor, neuroprotective effects, anti-diabetics, anti-inflammatory, anti-hyperlipidemia, etc. These therapeutic effects can be achieved with different mechanisms such as improvement of oxygenation in hypoxic tissues, antioxidant effects, inhibition of pro-inflammatory mediators, anti-proliferative activity and stimulation of apoptosis in cancer cells. It is also worth considering that crocetin could be tolerated without major toxicity at therapeutic dosage in experimental models. In the present review, we discuss the biosynthesis, pharmacokinetic properties of crocetin and provide a comprehensive study on the biological activities and toxicity along with the mechanism of actions and clinical trials data of crocetin.


Assuntos
Carotenoides/farmacologia , Carotenoides/toxicidade , Animais , Carotenoides/química , Carotenoides/farmacocinética , Humanos
5.
Nutrients ; 11(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991720

RESUMO

Sofrito is a Mediterranean tomato-based sauce that typically also contains olive oil, onion, and garlic. The preparation of sofrito modifies the bioactive compounds (carotenoids and polyphenols) in the ingredients to more bioavailable forms, promoting cis-lycopene formation and polyphenol bioaccessibility. To evaluate the health benefits of this cooking technique, the effect of consuming an acute dose of sofrito on the inflammatory status was studied. In a clinical trial, 22 healthy male subjects consumed a single dose of sofrito (240 g/70 kg) after three days without ingesting any tomato products and following a low-antioxidant diet the day before the intervention. Plasma carotenoids and total polyphenol excretion (TPE) were evaluated, as well as the inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL-6), interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). After the sofrito intake, a significant decrease in CRP (p = 0.010) and TNF-α (p = 0.011) was observed, but only TNF-α was inversely correlated with an increase in TPE and plasma ß-carotene (not the major carotenoid, lycopene). The positive health effects of this tomato-based product may be attributed not only to lycopene, but to the bioactive compounds of all the ingredients.


Assuntos
Allium/química , Carotenoides/farmacologia , Culinária/métodos , Inflamação/sangue , Lycopersicon esculentum/química , Olea/química , Polifenóis/farmacologia , Adolescente , Adulto , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Disponibilidade Biológica , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Carotenoides/farmacocinética , Carotenoides/uso terapêutico , Citocinas/sangue , Dieta Mediterrânea , Voluntários Saudáveis , Humanos , Inflamação/prevenção & controle , Licopeno/farmacocinética , Licopeno/farmacologia , Licopeno/uso terapêutico , Masculino , Azeite de Oliva/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polifenóis/farmacocinética , Polifenóis/uso terapêutico , Adulto Jovem , beta Caroteno/farmacocinética , beta Caroteno/farmacologia , beta Caroteno/uso terapêutico
6.
Nutrients ; 11(4)2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-31013870

RESUMO

A growing literature is dedicated to the understanding of carotenoid beneficial health effects. However, the absorption process of this broad family of molecules is still poorly understood. These highly lipophilic plant metabolites are usually weakly absorbed. It was long believed that ß-carotene absorption (the principal provitamin A carotenoid in the human diet), and thus all other carotenoid absorption, was driven by passive diffusion through the brush border of the enterocytes. The identification of transporters able to facilitate carotenoid uptake by the enterocytes has challenged established statements. After a brief overview of carotenoid metabolism in the human upper gastrointestinal tract, a focus will be put on the identified proteins participating in the transport and the metabolism of carotenoids in intestinal cells and the regulation of these processes. Further progress in the understanding of the molecular mechanisms regulating carotenoid intestinal absorption is still required to optimize their bioavailability and, thus, their health effects.


Assuntos
Carotenoides/metabolismo , Absorção Intestinal/fisiologia , Disponibilidade Biológica , Transporte Biológico , Carotenoides/química , Carotenoides/farmacocinética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Enterócitos/fisiologia , Análise de Alimentos , Regulação da Expressão Gênica/fisiologia , Humanos , Intestinos/fisiologia
7.
Food Chem ; 286: 678-685, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30827663

RESUMO

The effects of co-digestion of a carotenoid-rich vegetable such as carrot, cherry tomato or baby spinach with an anthocyanin-rich vegetable such as red cabbage with and without salad dressing on the intestinal cellular bioaccessibility (cBAC) of carotenoids and the resultant cellular antioxidant and anti-inflammatory activities were investigated. The % cBAC of lutein from the tested vegetables was 0.23-1.42%, lycopene 0.07-0.39%, α-carotene 0.01-0.12% and ß-carotene 0.03-0.61% respectively. The % cBAC of each of these carotenoids from the co-digested vegetables was significantly higher (p < 0.05) than from carrot, cherry tomato or baby spinach digested alone. % cBAC of total carotenoids was significantly increased by 46-191% (p < 0.05) as a result of the co-digestion. The vegetable co-digestion did not result in any impairment on the resultant cellular anti-oxidation and anti-inflammation (NO, IL-8 secretion). Among the tested vegetables, baby spinach co-digested with red cabbage showed synergistic bioactivities in all tested assays.


Assuntos
Antocianinas/farmacocinética , Carotenoides/farmacocinética , Verduras/química , Antioxidantes/análise , Antioxidantes/farmacologia , Disponibilidade Biológica , Brassica/metabolismo , Células CACO-2 , Carotenoides/análise , Digestão , Humanos , Luteína/farmacocinética , Licopeno/farmacocinética , Lycopersicon esculentum/química , Spinacia oleracea/química , beta Caroteno/farmacocinética
8.
Yakugaku Zasshi ; 139(3): 341-347, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30828009

RESUMO

Preventive medicine and anti-aging medicine have received much attention recently due to an increase in the proportion of elderly people in the population, and to an increase in patients with lifestyle diseases. Oxidative stress is involved in the onset of lifestyle diseases, and various antioxidant supplements and antioxidant-fortified functional foods have recently become available. Many epidemiological studies have shown relationships between the consumption of polyphenol and carotenoid-rich foods and the prevention of lifestyle diseases. We have focused on the absorption mechanism of these food components that show low bioavailability, and have made efforts to improve their poor absorption based on their pharmacokinetic properties. In this report, as examples, we describe the enhancement of the absorption of coenzyme Q10 (CoQ10) and lutein. To improve the absorption of CoQ10, we focused on the component of emulsion. We found that a higher plasma concentration of CoQ10 could be obtained by creating an emulsion containing a surfactant with a higher hydrophile-lipophile balance (HLB) value. For the improvement of lutein absorption, we prepared a solid dispersion and self-emulsifying drug delivery system. It was shown that the plasma concentrations of lutein in these two formulation groups were increased compared with that in the powder group. The absorption of lutein was also evaluated by its cumulative amount in the lymph system. Our data showed that lutein is transferred from the small intestine into the lymph stream, rather than into the blood stream. Further investigations to improve the absorption of these components are in progress.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Suplementos Nutricionais , Alimento Funcional , Luteína/administração & dosagem , Luteína/farmacocinética , Ubiquinona/análogos & derivados , Animais , Disponibilidade Biológica , Carotenoides/administração & dosagem , Carotenoides/farmacocinética , Sistemas de Liberação de Medicamentos , Emulsões , Alimento Funcional/análise , Humanos , Interações Hidrofóbicas e Hidrofílicas , Absorção Intestinal , Estilo de Vida , Sistema Linfático/metabolismo , Estresse Oxidativo , Polifenóis/administração & dosagem , Polifenóis/farmacocinética , Ratos , Tensoativos , Ubiquinona/administração & dosagem , Ubiquinona/farmacocinética
9.
J AOAC Int ; 102(4): 1044-1058, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786954

RESUMO

Carotenoids are typically tetraterpenoid phytochemicals that cannot be synthesized by humans, some of which such as ß-carotene can be metabolized into vitamin A. Sufficient carotenoid intake and tissue levels have been associated with several health benefits including the reduction of cardiovascular diseases and some types of cancer and also the amelioration of age-related macular degeneration. Carotenoids and their metabolites have also been related to reduced inflammation and oxidative stress via interacting with transcription factors, such as NF-κB and Nrf-2, as well as with the nuclear receptors retinoic acid receptor/retinoid X receptor, implicated in immune functions and cellular differentiation. Therefore, carotenoids are important for growth and development. They could mark beneficial constituents in infant food formulas and adult nutritionals, the latter typically constituting protein-rich liquid foods targeting meal replacements. Carotenoids may be present by nature (typically below 20 µg/100 mL) or following fortification (up to 200 µg/100 mL), such as for lutein and ß-carotene. However, carotenoid bioavailability may be low and variable, especially in low-fat items. Although most infant foods and adult nutritionals are rich in lipids and proteins, facilitating absorption and availability of carotenoids, unfortunately, very little data is available. In addition, carotenoid detection for such lipid-rich matrices may be challenging as a result of low concentrations and matrix effects. This review aims to highlight considerations for carotenoid bioavailability from infant food formula and adult nutritionals as well as summarize detection methods for carotenoids from these items.


Assuntos
Carotenoides/análise , Disponibilidade Biológica , Carotenoides/metabolismo , Carotenoides/farmacocinética , Laticínios/análise , Humanos , Lactente , Alimentos Infantis/análise , Fórmulas Infantis/análise
10.
Food Chem ; 285: 282-289, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30797346

RESUMO

Carotenoids are lipophilic compounds that are digested and absorbed along with lipids. Emulsions based on a mixture of plum tomato and red sweet pepper, with 5% or 10% rapeseed oil, were obtained by high pressure homogenization, and the concentration of carotenoids in the emulsion oil droplets was quantified. The fraction of lycopene and beta-carotene released from the plant matrix into the oil droplets was highest in the 10% emulsion, which had larger oil droplets than the 5% emulsion. Xanthophylls were easily released into oil droplets in both 5% and 10% emulsions. The results suggest that the release of carotenoids made available for intestinal absorption depends on carotenoid type and can be significantly improved by increasing the homogenization pressure and oil content. However, in vitro gastrointestinal digestion indicated the presence of constituents or structures in the emulsions, originating from tomato, that reduced pancreatic activity, which may delay micellarization and uptake of carotenoids.


Assuntos
Capsicum/química , Carotenoides/farmacocinética , Emulsões/química , Lipídeos/farmacocinética , Lycopersicon esculentum/química , Carotenoides/análise , Carotenoides/química , Cromatografia Líquida de Alta Pressão , Digestão , Humanos , Absorção Intestinal , Lipídeos/química , Licopeno/análise , Licopeno/farmacocinética , Pressão , Óleo de Brassica napus/química , Análise Espectral Raman , Xantofilas/farmacocinética , beta Caroteno/análise , beta Caroteno/farmacocinética
11.
Mol Nutr Food Res ; 63(15): e1801046, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30698921

RESUMO

Vision depends on the delivery of vitamin A (retinol) to the retina. Retinol in blood is bound to retinol-binding protein (RBP). Retinal pigment epithelia (RPE) cells express the RBP receptor, STRA6, that facilitates uptake of retinol. The retinol is then converted to retinyl esters by the enzyme lecithin:retinol acyltransferase. The esters are the substrate for RPE65, an enzyme that produces 11-cis retinol, which is converted to 11-cis retinaldehyde for transport to the photoreceptors to form rhodopsin. The dietary xanthophylls, lutein (LUT) and zeaxanthin (ZEA), accumulate in the macula of the eye, providing protection against age-related macular degeneration. To reach the macula, carotenoids cross the RPE. In blood, xanthophylls and ß-carotene mostly associate with high-density lipoprotein (HDL) and low-density lipoprotein (LDL), respectively. Studies using a human RPE cell model evaluate the kinetics of cell uptake when carotenoids are delivered in LDL or HDL. For LUT and ß-carotene, LDL delivery result in the highest rate of uptake. HDL is more effective in delivering ZEA (and meso-ZEA). This selective HDL-mediated uptake of ZEA, via a scavenger receptor and LDL-mediated uptake of LUT and ß-carotene provides a mechanism for the selective accumulation of ZEA > LUT and xanthophylls over ß-carotene in the macula.


Assuntos
Carotenoides/farmacocinética , Epitélio Pigmentado da Retina/metabolismo , Vitamina A/farmacocinética , Animais , Carotenoides/metabolismo , Dieta , Humanos , Absorção Intestinal/efeitos dos fármacos , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Vitamina A/metabolismo
12.
Food Chem ; 279: 321-327, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30611497

RESUMO

With in-vitro digestion and human intestinal HepG2 cells, we analyzed the bioaccessibility and cell uptake of phytochemicals and determined the cellular antioxidant capacity (CAA) of fresh eating citrus fruits. The results showed that CAA of citrus fruits was higher in digesta than in extracts, and the CAA is strongly correlated with naringenin and beta-carotene uptake (p < 0.05). During in vitro digestion, vanillic acid and p-coumaric decreased, and ferulic acid increased in all citrus fruits significantly (p < 0.05); other phytochemicals varied among the fruits. During uptake, hydroxybenzoic acids, hesperidin, narirutin, naringenin and neohesperidin were detected in cells, Zeaxanthin, lutein, beta-cryptoxanthin and beta-carotene could be detected in the citrus varieties except for pummel, but hydroxycinnamic acids and hesperitin were not detected in cells. This work provides insights into the bioaccessibility and cell uptake of phytochemicals and cellular antioxidant activity of fresh eating citrus fruits.


Assuntos
Antioxidantes/análise , Carotenoides/análise , Citrus/química , Flavonoides/análise , Hidroxibenzoatos/análise , Disponibilidade Biológica , Carotenoides/farmacocinética , Digestão , Flavonoides/farmacocinética , Frutas/química , Células Hep G2 , Humanos , Hidroxibenzoatos/farmacocinética
13.
Nutr Res ; 61: 95-101, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683442

RESUMO

Carotenoids are phytochemicals with strong antioxidant activity against reactive oxygen species that are widely distributed in fruits and vegetables. The beneficial effects of carotenoids on human health have attracted considerable attention. The plasma carotenoid profile in humans is generally recognized to reflect the dietary carotenoid composition. Although carotenoid profile in plasma is believed to correlate well with that in other tissues, the data for tissue accumulation of carotenoids in humans is very limited and poorly understood. In order to test the hypothesis that blood carotenoids reflect tissue accumulation of dietary carotenoids, the cynomolgus monkey was used as a model to determine it's suitable for extrapolation of data on tissue accumulation of carotenoids to humans. Herein, plasma carotenoids were measured in cynomolgus monkeys given a dietary mixture of carotenoids. The findings indicate that cynomolgus monkeys and humans are similar with regard to preferential accumulation of ß-cryptoxanthin in the blood and brain. These results suggested that cynomolgus monkeys could be used to collect data on tissue accumulation of carotenoids for extrapolation to humans. The tissue accumulation of carotenoids in other tissues of cynomolgus monkeys that have not yet been evaluated in humans were also investigated, revealing marked differences in carotenoid levels and composition among plasma and various monkey tissues. These results suggest that accumulation of carotenoids in plasma does not reflect necessarily that in tissues, so that predicting the tissue accumulation of carotenoids from plasma carotenoid levels and profiles alone could lead to errors.


Assuntos
Encéfalo/metabolismo , Carotenoides/metabolismo , Dieta , Modelos Animais , Plasma/metabolismo , Projetos de Pesquisa/normas , Animais , beta-Criptoxantina/sangue , beta-Criptoxantina/metabolismo , Viés , Carotenoides/sangue , Carotenoides/farmacocinética , Humanos , Macaca fascicularis , Masculino , Distribuição Tecidual
14.
Planta Med ; 85(3): 258-265, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30206907

RESUMO

Crocin and crocetin are two interesting constituents of saffron (Crocus sativus) that possess important biological activities. Their use as therapeutic agents is strongly compromised by a scarce stability, poor absorption, and low bioavailability. Therefore, to improve these unfavorable features, the aim of the present work has been to apply a nanotechnological approach based on the formulation of solid lipid nanoparticles containing crocin and crocetin. Solid lipid nanoparticles were formulated according to crocin and crocetin chemical properties, using a variation of the quasi-emulsion solvent diffusion method to formulate crocin-solid lipid nanoparticles, while crocetin-solid lipid nanoparticles were prepared following the solvent diffusion method. Morphology and dimensional distribution of solid lipid nanoparticles have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively, while the effect of drug incorporation versus time has been studied by Turbiscan technology. In order to verify the role of the nanotechnological approach on the biological activities of crocin and crocetin, the antioxidant and antiproliferative effects of these carotenoids once incorporated in lipid nanoparticles have been evaluated. For this aim, the oxygen radical absorbance capacity assay and the MTT test were used, respectively.The results pointed out the formulation of nanometric dispersions endowed with high homogeneity and stability, with an encapsulation efficiency ranging from 80 (crocetin-solid lipid nanoparticles) to 94% (crocin-crocetin). The oxygen radical absorbance capacity assay evidenced an interesting and prolonged antioxidant activity of crocin and crocetin once encapsulated in solid lipid nanoparticles, while the nanoencapsulation strategy showed a different mechanism in ameliorating the cytotoxic effect of these two substances.


Assuntos
Antioxidantes/administração & dosagem , Carotenoides/administração & dosagem , Citotoxinas/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antioxidantes/farmacocinética , Disponibilidade Biológica , Carotenoides/farmacocinética , Linhagem Celular Tumoral , Citotoxinas/farmacocinética , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas
15.
Biomed Pharmacother ; 109: 1211-1220, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551371

RESUMO

The study was designed to determine the safety and pharmacokinetics of intraocular crocetin and examine whether crocetin inhibits the development of proliferative vitreoretinopathy (PVR) in a rabbit model. In the toxicity study, the right eyes of rabbits were injected with 0.2 µmol or 0.4 µmol crocetin. The left eyes were injected with 0.1 ml phosphate buffered saline (PBS) containing the same concentration of DMSO. Fundus photography, optical coherence tomography (OCT), and electroretinogram (ERG) were obtained at baseline and 14 days. Afterward, the eyes were enucleated for histopathological analysis and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay. In the pharmacokinetic study, the eyes received an intravitreous injection of 0.4 µmol crocetin to detect vitreous drug levels with HPLC at specific time points. In the efficacy study, PVR was induced with an intravitreal injection of ARPE-19 cells in rabbits. Then ten eyes were injected with 0.4 µmol crocetin, and the other 10 eyes received 0.1 ml PBS. Fundus photography, OCT and ERG were performed at days 3 and 7 and weekly for a total of 4 weeks after injection. Afterward, the eyes were enucleated and subjected to histological analysis and TUNEL staining. The results demonstrated no signs of retinal toxicity. Intravitreal injection of 0.4 µmol crocetin had a half-life of 4.231 h. Treatment with crocetin significantly inhibited the progression of PVR in parallel with a reduced expression of α-SMA, collagen fibers and Ki67. These results indicate that crocetin is an effective and safe inhibitor of PVR in rabbit models.


Assuntos
Carotenoides/efeitos adversos , Carotenoides/farmacocinética , Injeções Intravítreas/efeitos adversos , Vitreorretinopatia Proliferativa/tratamento farmacológico , Animais , Carotenoides/administração & dosagem , Linhagem Celular , Modelos Animais de Doenças , Eletrorretinografia/métodos , Humanos , Coelhos , Retina/efeitos dos fármacos
16.
J Pharm Pharmacol ; 71(5): 753-764, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30575029

RESUMO

OBJECTIVES: To prepare a lyophilized saffron aqueous extract (SFE) and determine its chemical profile and serum and tissue pharmacokinetics after intravenous and oral administration to C57/Bl6J mice. METHODS: Lyophilized SFE was prepared, characterized using semi-preparative HPLC and NMR analysis, and stability studies at room temperature, and was quantified for crocin content with an HPLC-PDA method. After intravenous and oral administration of SFE (60 mg/kg, reconstituted with water for injection) to C57/Bl6J mice, crocetin (derived from in vivo crocin hydrolysis) serum and tissue levels (unconjugated and total) were measured with an HPLC-PDA method and subjected to compartmental and non-compartmental PK analysis. KEY FINDINGS: Saffron aqueous extract was rich in all-trans-crocin (27.8 ± 0.1% w/w) and stable for more than 15 months. One-compartment PK model described crocetin's (unconjugated) kinetics after intravenous administration of SFE, while a first-order kinetic parameter described the rate of crocetin biotransformation to crocetin metabolite (conjugated). Α οne-compartment PK model with first-order absorption described crocetin and crocetin's metabolite kinetics after SFE oral administration. Relative oral bioavailability was calculated at 1.17 for total crocetin. Tissue NCA PK analysis revealed extensive crocetin distribution to liver and kidneys. CONCLUSIONS: SFE is a stable lyophilized extract rich in all-trans-crocin. The PK study allowed the estimation of basic PK parameters and the bioavailability of SFE's main bioactive component, crocetin, after peros administration.


Assuntos
Carotenoides/química , Carotenoides/farmacocinética , Administração Intravenosa , Administração Oral , Animais , Disponibilidade Biológica , Carotenoides/administração & dosagem , Carotenoides/sangue , Crocus/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Distribuição Aleatória
17.
Mar Drugs ; 16(10)2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30360450

RESUMO

The benefit of carotenoids to human health is undeniable and consequently, their use for this purpose is growing rapidly. Additionally, the nutraceutical properties of carotenoids have attracted attention of the food industry, especially in a new market area, the 'cosmeceuticals.' Marine organisms (microalgae, seaweeds, animals, etc.) are a rich source of carotenoids, with optimal properties for industrial production and biotechnological manipulation. Consequently, several papers have reviewed the analysis, characterization, extraction and determination methods, biological functions and industrial applications. But, now, the bioaccessibility and bioactivity of marine carotenoids has not been focused of any review, although important achievements have been published. The specific and diverse characteristic of the marine matrix determines the bioavailability of carotenoids, some of them unique in the nature. Considering the importance of the bioavailability not just from the health and nutritional point of view but also to the food and pharmaceutical industry, we consider that the present review responds to an actual demand.


Assuntos
Organismos Aquáticos/química , Carotenoides/química , Carotenoides/farmacocinética , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Disponibilidade Biológica , Carotenoides/farmacologia , Humanos , Xantofilas/química , Xantofilas/farmacocinética , Xantofilas/farmacologia
18.
Curr Opin Clin Nutr Metab Care ; 21(6): 489-497, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30277929

RESUMO

PURPOSE OF REVIEW: To provide an update on the genetic factors recently associated with the interindividual variability of tomato carotenoid bioavailability. RECENT FINDINGS: Several clinical studies have demonstrated that the main carotenoids found in tomatoes (lycopene, phytoene, phytofluene, ß-carotene, lutein) all display relatively large interindividual variabilities of their bioavailability, with coefficients of variations more than 70%. The bioavailability of the parent molecules, and the blood/tissue appearance of their metabolites, is modulated by numerous proteins, involved in intestinal absorption and metabolism, blood lipoprotein transport or tissue uptake. Several single nucleotide polymorphisms (SNPs) have been associated with the interindividual variability of lycopene, lutein and ß-carotene bioavailability, with six genes consistently shared between the three carotenoids, and in particular one SNP in ELOVL fatty acid elongase 2. The effects of the genetic variants taken separately are relatively low, that is each variant is usually associated with only a few percentage of the variability but multivariate analyses suggest that the additive effect of several genetic variants can explain a significant fraction of tomato carotenoid bioavailability. SUMMARY: Additional studies are needed to improve our knowledge of the genetic determinants of tomato carotenoid bioavailability but progress in this field could one day allow nutritionists to provide more personalized dietary recommendations.


Assuntos
Carotenoides/farmacocinética , Absorção Intestinal/genética , Lycopersicon esculentum/química , Polimorfismo de Nucleotídeo Único , Disponibilidade Biológica , Humanos , Licopeno/farmacocinética , beta Caroteno/farmacocinética
19.
Mol Nutr Food Res ; 62(22): e1800703, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30192047

RESUMO

SCOPE: Absorption mechanisms of phytoene (PT) and phytofluene (PTF) are poorly known. The main objectives of the study are to measure their micellization and intestinal cell uptake efficiencies and to compare them to those of commonly consumed carotenoids. Other objectives are to assess the involvement of protein(s) in their cellular uptake and whether they compete with other carotenoids for micellization and cellular uptake. METHODS AND RESULTS: Tomato-extract-purified PT and PTF, mainly present as cis-isomers, are much better incorporated in synthetic mixed micelles than pure all-trans lycopene. PT impairs lycopene micellization (-56%, P < 0.05) while PT and PTF do not significantly affect the micellization of other carotenoids, and vice versa. At low concentration, Caco-2 PTF uptake is higher (P < 0.05) than that of PT and lycopene (29%, 21%, and not detectable). SR-BI, but not CD36 neither NPC1L1, is involved in PT and PTF uptake. PT and PTF impair (p < 0.05) ß-carotene uptake (-13 and -22%, respectively). CONCLUSIONS: The high bioaccessibility of PT and PTF can be partly explained by their high micellization efficiency, which is likely due to their natural cis isomerization and/or to their high molecular flexibility. SR-BI is involved in their cellular uptake, which can explain competitions with other carotenoids.


Assuntos
Carotenoides/farmacocinética , Lycopersicon esculentum/química , Receptores Depuradores Classe B/metabolismo , Azetidinas/farmacologia , Disponibilidade Biológica , Células CACO-2 , Carotenoides/química , Carotenoides/isolamento & purificação , Glucuronídeos/farmacologia , Humanos , Licopeno/isolamento & purificação , Licopeno/farmacocinética , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Micelas , Extratos Vegetais/química , Receptores Depuradores Classe B/antagonistas & inibidores
20.
Adv Nutr ; 9(5): 625-636, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239582

RESUMO

The ability of nutrition scientists to measure the status, bioavailability, and bioefficacy of micronutrients is affected by lack of access to the parts of the body through which a nutrient may travel before appearing in accessible body compartments (typically blood or urine). Stable isotope-labeled tracers function as safe, nonradioactive tools to follow micronutrients in a quantitative manner because the absorption, distribution, metabolism, and excretion of the tracer are assumed to be similar to the unlabeled vitamin or mineral. The International Atomic Energy Agency (IAEA) supports research on the safe use of stable isotopes in global health and nutrition. This review focuses on IAEA's contributions to vitamin A, iron, and zinc research. These micronutrients are specifically targeted by the WHO because of their importance in health and worldwide prevalence of deficiency. These 3 micronutrients are included in food fortification and biofortification efforts in low- and middle-income regions of the world. Vitamin A isotopic techniques can be used to evaluate the efficacy and effectiveness of interventions. For example, total body retinol stores were estimated by using 13C2-retinol isotope dilution before and after feeding Zambian children maize biofortified with ß-carotene to determine if vitamin A reserves were improved by the intervention. Stable isotopes of iron and zinc have been used to determine mineral bioavailability. In Thailand, ferrous sulfate was better absorbed from fish sauce than was ferrous lactate or ferric ammonium citrate, determined with the use of different iron isotopes in each compound. Comparisons of one zinc isotope injected intravenously with another isotope taken orally from a micronutrient powder proved that the powder increased total absorbed zinc from a meal in Pakistani infants. Capacity building by the IAEA with appropriate collaborations in low- and middle-income countries to use stable isotopes has resulted in many advancements in human nutrition.


Assuntos
Marcação por Isótopo/métodos , Micronutrientes/farmacocinética , Avaliação Nutricional , Ciências da Nutrição/métodos , Adulto , Disponibilidade Biológica , Carotenoides/farmacocinética , Criança , Feminino , Humanos , Ferro/farmacocinética , Isótopos/farmacocinética , Masculino , Estado Nutricional , Vitamina A/farmacocinética , Zinco/farmacocinética
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