RESUMEN
Coenzyme Q10 (CoQ10) exerts its functions in the body through the ability of its benzoquinone head group to accept and donate electrons. The primary functions are to relay electrons for ATP production in the electron transport chain and to act as an important lipophilic antioxidant. Ubiquinone, the oxidized form of CoQ10, is commonly formulated in commercial supplements, and it must be reduced to ubiquinol to exert CoQ10's functions after consumption. Thus, we aimed to examine whether as compared to ubiquinone, ubiquinol would be more effective to enhance the CoQ10 status in older men. We conducted a double-blind, randomized, crossover trial with two 2-week intervention phases and a 2-week washout between crossovers. Ten eligible older men were randomized to consume either the ubiquinol or ubiquinone supplement at a dose of 200 mg d-1 with one of the main meals. A total of 4 blood samples were collected after an overnight fast for the determination of ubiquinone and ubiquinol in plasma and PBMC and the assessment of FRAP, total thiol, and malondialdehyde (MDA) in plasma and ATP in PBMC. After 2 weeks of the supplementation, the ubiquinol supplement significantly increased plasma ubiquinone 1.7 fold from 0.2 to 0.6 µmol L-1 and total CoQ10 (the sum of 2 forms) 1.5 fold from 1.3 to 3.4 µmol L-1 (p < 0.05) and tended to increase the plasma ubiquinol status 1.5 fold from 1.1 to 2.8 µmol L-1, but did not alter the ratio of ubiquinol to total CoQ10. The ubiquinone supplement insignificantly increases plasma ubiquinol, ubiquinone, and total CoQ10 and did not affect the ratio. Of 10 subjects, six were more responsive to the ubiquinol supplement and 2 were more so to the ubiquinone. The supplementation of both CoQ10 forms did not alter the CoQ10 status in PBMC. FRAP, total thiol, and MDA in plasma and ATP in PBMC were not changed during the intervention. The significant increase in plasma CoQ10 status observed after the 2-week supplementation suggested that ubiquinol appeared to be a better supplemental form to enhance the CoQ10 status than ubiquinone in older men. Neither ubiquinol nor ubiquinone supplement affected the measured biomarkers of oxidative stress.
Asunto(s)
Suplementos Dietéticos , Ubiquinona/análogos & derivados , Ubiquinona/administración & dosificación , Anciano , Antioxidantes/farmacología , Biomarcadores/sangre , Índice de Masa Corporal , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Ubiquinona/sangreRESUMEN
The dietary phenol tyrosol has been reported to be endogenously transformed into hydroxytyrosol, a potent antioxidant with multiple health benefits. In this work, we evaluated whether tyrosine hydroxylase (TH) and cytochrome P450s (CYPs) catalyzed this process. To assess TH involvement, Wistar rats were treated with α-methyl-L-tyrosine and tyrosol. Tyrosol was converted into hydroxytyrosol whilst α-methyl-L-tyrosine did not inhibit the biotransformation. The role of CYP was assessed in human liver microsomes (HLM) and tyrosol-to-hydroxytyrosol conversion was observed. Screening with selective enzymatic CYP inhibitors identified CYP2A6 as the major isoform involved in this process. Studies with baculosomes further demonstrated that CYP2D6 and CYP3A4 could transform tyrosol into hydroxytyrosol. Experiments using human genotyped livers showed an interindividual variability in hydroxytyrosol formation and supported findings that CYP2D6 and CYP2A6 mediated this reaction. The dietary health benefits of tyrosol-containing foods remain to be evaluated in light of CYP pharmacogenetics.
Asunto(s)
Citocromo P-450 CYP2A6/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Alcohol Feniletílico/análogos & derivados , Animales , Antioxidantes/metabolismo , Biotransformación , Humanos , Masculino , Microsomas Hepáticos/metabolismo , Alcohol Feniletílico/metabolismo , Ratas , Ratas Wistar , Tirosina/metabolismoRESUMEN
The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein uptake and secretion was also assessed in Caco-2 cells. Compared to free lutein, PLGA-NP increased the maximal plasma concentration (Cmax) and area under the time-concentration curve in rats by 54.5- and 77.6-fold, respectively, while promoting tissue accumulation in the mesenteric fat and spleen. In comparison with micellized lutein, PLGA-NP lutein improved the Cmax in rat plasma by 15.6-fold and in selected tissues by ⩾ 3.8-fold. In contrast, PLGA-NP lutein had a lower uptake and secretion of lutein in Caco-2 cells by 10.0- and 50.5-fold, respectively, compared to micellized lutein. In conclusion, delivery of lutein with polymeric NP may be an approach to improve the bioavailability of lutein in vivo.
Asunto(s)
Disponibilidad Biológica , Células CACO-2/química , Luteína/química , Nanopartículas/química , Distribución Tisular/fisiología , Animales , Humanos , Masculino , RatasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium aurantiacum var. denneanumis widespread in southern China, locally known as "Shihu", "Huangcao" or "Fengdou", has long been used in traditional Chinese medicine for antipyretic, immunomodulatory, anti-aging effects and eye benefiting. AIM OF THIS STUDY: To investigate the effects of gigantol extracted from the stem of D. aurantiacum var. denneanum on the formation of galactose-induced cataractogenesis and the potential mechanisms underlying these effects. MATERIALS AND METHODS: Cataract lens models were induced by d-galactose both in vitro and in vivo. The transparency of the rat lenses in vitro and in vivo was observed with an anatomical microscope and a slit lamp microscope. The differential protein and action targets of gigantol were determined and compared among the control group, model group, and gigantol group using two-dimensional electrophoresis and mass spectrometry (MS). Enzyme kinetics was used to show the ability of gigantol to respress aldose reductase (AR) and inducible nitric oxide synthase (iNOS). Quantitative real-time PCR (RT-qPCR). was used to detect repression of the expression of AR and iNOS genes. Molecular docking and dynamic simulation were used to predict the interaction points and combination patterns between gigantol, AR, and iNOS. RESULTS: Gigantol was found to prevent galactose-induced damage to the rat lenses both in vitro and in vivo, to delay lens turbidity, and to keep the lenses transparent. Differential proteomes, MS, and RT-qPCR showed AR and iNOS to be the target proteins of gigantol. Gigantol reduced the galactose-induced AR and iNOS mRNA expression by 51.2% and 60.9%, respectively. The IC50 of gigantol for inhibition of AR and iNOS activities were 65.67 µg/mL and 8.768 µg/mL, respectively. Gigantol-AR binding sites were Trp111, His110, Tyr48, and Trp20, and gigantol-iNOS binding sites were Ile195 and Gln257. The main forms of interaction were hydrophobic forces, hydrogen bonds, and van der Waals forces. CONCLUSION: Gigantol extracted from D. aurantiacum var. denneanum was found to inhibit galactose-induced formation of cataracts through repression of the gene expression and activity of AR and iNOS.
Asunto(s)
Antioxidantes/farmacología , Bibencilos/farmacología , Catarata/prevención & control , Dendrobium/química , Guayacol/análogos & derivados , Animales , Antioxidantes/aislamiento & purificación , Bibencilos/aislamiento & purificación , Catarata/etiología , Medicamentos Herbarios Chinos , Galactosemias/complicaciones , Guayacol/aislamiento & purificación , Guayacol/farmacología , Cristalino/efectos de los fármacos , Cristalino/patología , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Presión Osmótica/efectos de los fármacos , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
UV exposure causes oxidative stress, inflammation, erythema, and skin cancer. α-Tocopherol (AT) and polyphenols (AP) present in almonds may serve as photoprotectants. Our objectives were to assess the feasibility of using a 3D human skin equivalent (HSE) in photoprotectant research and to determine photoprotection of AT and AP against UVA radiation. AT or AP was applied to medium (25 and 5µmol/L, respectively) or topically (1mg/cm(2) and 14µg/cm(2)), followed by UVA. Photodamage assessed 96h post UVA included HSE morphology, keratinocyte proliferation, apoptosis, and differentiation. UVA induced disorganization of basal layer, alteration of epidermal development, and fibroblast loss which were alleviated by all nutrient pretreatments. UVA significantly decreased keratinocyte proliferation compared to controls, and all pretreatments tended to negate the reduction though only the medium AT effect was statistically significant (p⩽0.05). UVA led to a significant 16-fold increase in apoptosis of fibroblasts compared to the control which was alleviated by topical AP pretreatment and completely negated by topical AT (p⩽0.05). In conclusion, we validated the feasibility of using HSE in evaluation of photoprotectants and found that AT and AP, applied to medium or topically, provided some degree of photoprotection against UVA.
Asunto(s)
Polifenoles/farmacología , Prunus/química , Protectores contra Radiación/farmacología , Piel/efectos de los fármacos , Piel/efectos de la radiación , alfa-Tocoferol/farmacología , Absorción , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Bovinos , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Dieta , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Proyectos Piloto , Polifenoles/metabolismo , Protectores contra Radiación/metabolismo , Piel/citología , Rayos Ultravioleta/efectos adversos , alfa-Tocoferol/metabolismoRESUMEN
UNLABELLED: The extent to which sample dilution factor (DF) affects total antioxidant capacity (TAC) values is poorly understood. Thus, we examined the impact of DF on the ORAC, FRAP, DPPH, and total phenols (TP) assays using pomegranate juice (PJ), grape juice (GJ), selected flavonoids, ascorbic acid, and ellagic acid. For ORAC, GJ was comparable to PJ at DF 750, but at DF 2000, the ORAC value of GJ was 40% more than PJ. Increasing DF increased GJ and PJ, DPPH, TP, and FRAP values 11% and 14%, respectively. Increased test concentrations of quercetin and catechin resulted in 51% and 126% greater ORAC values, but decreased naringenin by 68%. Flavonoids, but not ellagic acid or ascorbic acid, may contribute to the dilution effect on the variation of final TAC values. Thus, reporting TAC or TP using a single DF may introduce uncertainty about the confidence of TAC assay values, especially when comparing different juices. These results underscore the importance of using compatible test standards for reporting TAC values. PRACTICAL APPLICATION: Total antioxidant capacity (TAC) values such as the ORAC assay are increasingly used for comparison of polyphenol-rich foods and beverages. Choice of standards and test concentrations, even within the linear range of standards, may introduce variation probably due to synergy/antagonism between antioxidant and thereby, confound final TAC values. Thus, test concentration or dilution factors of samples should be considered in the design of TAC assays and interpretation of their results.
Asunto(s)
Antioxidantes/análisis , Bebidas/análisis , Bioensayo/métodos , Frutas/química , Polifenoles/análisis , Ácido Ascórbico/análisis , Catequina/análisis , Ácido Elágico/análisis , Modelos Lineales , Lythraceae/química , Quercetina/análisis , Especies Reactivas de Oxígeno/metabolismo , Vitis/químicaRESUMEN
Reverse phase HPLC coupled to negative mode electrospray ionization (ESI) mass spectrometry (MS) was used to quantify 16 flavonoids and 2 phenolic acids from almond skin extracts. Calibration curves of standard compounds were run daily and daidzein was used as an internal standard. The inter-day relative standard deviation (RSD) of standard curve slopes ranged from 13% to 25% of the mean. On column (OC) limits of detection (LOD) for polyphenols ranged from 0.013 to 1.4 pmol, and flavonoid glycosides had a 7-fold greater sensitivity than aglycones. Limits of quantification were 0.043 to 2.7 pmol OC, with a mean of 0.58 pmol flavonoid OC. Mean inter-day RSD of polyphenols in almond skin extract was 6.8% with a range of 4% to 11%, and intra-day RSD was 2.4%. Liquid nitrogen (LN(2)) or hot water (HW) blanching was used to facilitate removal of the almond skins prior to extraction using assisted solvent extraction (ASE) or steeping with acidified aqueous methanol. Recovery of polyphenols was greatest in HW blanched almond extracts with a mean value of 2.1 mg/g skin. ASE and steeping extracted equivalent polyphenols, although ASE of LN(2) blanched skins yielded 52% more aglycones and 23% less flavonoid glycosides. However, the extraction methods did not alter flavonoid profile of HW blanched almond skins. The recovery of polyphenolic components that were spiked into almond skins before the steeping extraction was 97% on a mass basis. This LC-MS method presents a reliable means of quantifying almond polyphenols.
Asunto(s)
Cromatografía Líquida de Alta Presión , Flavonoides/análisis , Fenoles/análisis , Prunus/química , Semillas/química , Espectrometría de Masa por Ionización de Electrospray , Polifenoles , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIM: Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals. METHODS: Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F(2alpha) (8-epi PGF(2alpha)) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention. RESULTS: Urinary 8-epi PGF(2alpha) decreased (-22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females. CONCLUSIONS: Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress.