Dietary Intake of Fructooligosaccharides Protects against Metabolic Derangements Evoked by Chronic Exposure to Fructose or Galactose in Rats.

SCOPE: Diets rich in fat and sugars evoke chronic low-grade inflammation, leading to metabolic derangements. This study investigates the impact of fructose and galactose, two commonly consumed simple sugars, on exacerbation of the harmful effects caused by high fat intake. Additionally, the potential efficacy of fructooligosaccharides (FOS), a fermentable dietary fiber, in counteracting these effects is examined. METHODS AND RESULTS: Male Sprague-Dawley rats (six/group) are fed 8 weeks as follows: control 5% fat diet (CNT), 20% fat diet (FAT), FAT+10% FOS diet (FAT+FOS), FAT+25% galactose diet (FAT+GAL), FAT+GAL+10% FOS diet (FAT+GAL+FOS), FAT+25% fructose diet (FAT+FRU), FAT+FRU+10% FOS diet (FAT+FRU+FOS). The dietary manipulations tested do not affect body weight gain, blood glucose, or markers of systemic inflammation whereas significant increases in plasma concentrations of triacylglycerols, cholesterol, aspartate aminotransferase, and alanine aminotrasferase are detected in both FAT+FRU and FAT+GAL compared to CNT. In the liver and skeletal muscle, both sugars induce significant accumulation of lipids and advanced glycation end-products (AGEs). FOS supplementation prevents these impairments. CONCLUSION: This study extends the understanding of the deleterious effects of a chronic intake of simple sugars and demonstrates the beneficial role of the prebiotic FOS in dampening the sugar-induced metabolic impairments by prevention of lipid and AGEs accumulation.

The Pharmacokinetics of Individual Conjugated Xanthohumol Metabolites Show Efficient Glucuronidation and Higher Bioavailability of Micellar than Native Xanthohumol in a Randomized, Double-Blind, Crossover Trial in Healthy Humans.

SCOPE: Prenylated chalcones and flavonoids are found in many plants and are believed to have beneficial effects on health when consumed. Xanthohumol is present in beer and likely the most consumed prenylated chalcone, but poorly absorbed and rapidly metabolized and excreted, thus limiting its bioavailability. Micellar formulations of phytochemicals have been shown to improve bioavailability. METHODS AND RESULTS: In a randomized, double-blind, crossover trial with five healthy (three males and two females) volunteers, a single dose of 43 mg was orally administered as a native or micellar formulation. The major human xanthohumol metabolites are quantified in plasma. Unmetabolized free xanthohumol makes 1% or less of total plasma xanthohumol. The area under the plasma concentration-time curve of xanthohumol-7-O-glucuronide following the ingestion of the micellular formulation is 5-fold higher and its maximum plasma concentration is more than 20-fold higher compared to native xanthohumol. CONCLUSION: Metabolism of orally ingested xanthohumol is complex and efficiently converts the parent compound to predominantly glucuronic acid and to a lesser extent sulfate conjugates. The oral bioavailability of micellar xanthohumol is superior to native xanthohumol, making it a useful delivery form for future human trials.

Prumnopitys Andina Fruit Extract Activates Liver X Receptors after In Vitro Digestion.

SCOPE: 20-Hydroxyecdysone (20E) is the main phytochemical present in the fresh arils of Prumnopitys andina. 20E is reported to have anabolic effects by modulation of gene transcription by interaction with nuclear receptors. Our aim is to evaluate the in vitro bioaccessibility, transepithelial transport of 20E, and the capacity of P. andina fruit extract and 20E to activate selected mammalian nuclear receptors in transiently transfected human cells after simulated gastrointestinal digestion. RESULTS: 20E shows good stability, solubility, and micellization after in vitro digestion. 20E is taken up by Caco-2 cells, but poorly transported through the epithelial cell membrane, possibly due to P-glycoprotein-mediated efflux. In transiently transfected HepG2 cells, the fruit extract significantly induces the signal intensity for the liver X receptor (LXR)-α and -ß by 1.6 and 1.4-fold, respectively. In contrast, the treatment with 20E, irrespective of its concentration, did not change the activity of both LXR receptors. No effects are observed for the pregnane X receptor or the constitutive androstane receptor. CONCLUSION: Our findings show that components of the digested P. andina extract other than 20E are responsible for the effects on LXR-α and -ß. Our findings open new perspectives on the potential role of P. andina fruits in cholesterol metabolism and inflammatory diseases.

Micellar Curcumin: Pharmacokinetics and Effects on Inflammation Markers and PCSK-9 Concentrations in Healthy Subjects in a Double-Blind, Randomized, Active-Controlled, Crossover Trial.

SCOPE: Preclinical models have demonstrated the anti-inflammatory and lipid-lowering effects of curcumin. Innovative formulations have been developed to overcome the poor bioavailability of native curcumin. The study hypothesizes that the bioavailability of micellar curcumin is superior to native curcumin and investigates the potential anti-inflammatory and proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration lowering effects. METHODS AND RESULTS: In this double-blind, randomized, crossover trial, 15 healthy volunteers receive micellar or native curcumin (105 mg day-1 ) for 7 days with a ≥7 days washout period. Curcumin and metabolite concentrations are quantified by high-performance liquid chromatography with fluorescence detection (HPLC-FD), and pharmacokinetics are calculated. To analyze anti-inflammatory effects, blood samples (baseline, 2 h, 7 days) are stimulated with 50 ng mL-1 lipopolysaccharides (LPS). Interleukin (IL)-6, tumor-necrosis factor (TNF-α), and PCSK9 concentrations are quantified. Micellar curcumin demonstrates improved bioavailability (≈39-fold higher maximum concentrations, ≈14-fold higher area-under-the-time-concentration curve, p < 0.001) but does not reduce pro-inflammatory cytokines in the chosen model. Subjects receiving micellar curcumin have significantly lower PCSK9 concentrations (≈10% reduction) after 7 days compared to baseline (p = 0.038). CONCLUSION: Micellar curcumin demonstrates an improved oral bioavailability but does not show anti-inflammatory effects in this model. Potential effects on PCSK9 concentrations warrant further investigation.

Vitamin E and carotenoid profiles in leaves, stems, petioles and flowers of stinging nettle (Urtica leptophylla Kunth) from Costa Rica.

BACKGROUND: Local leafy vegetables are gaining attention as affordable sources of micronutrients, including vitamins, pro-vitamin carotenoids and other bioactive compounds. Stinging nettles (Urtica spp.) are used as source of fibers, herbal medicine and food. However, despite the relatively wide geographical spread of Urtica leptophylla on the American continent, little is known about its content of vitamin E congeners and carotenoids. We therefore investigated the particular nutritional potential of different plant structures of wild Costa Rican U. leptophylla by focusing on their vitamin E and carotenoid profiles. RESULTS: Young, mature and herbivore-damaged leaves, flowers, stems and petioles were collected and freeze-dried. Vitamin E and carotenoids were determined by high-performance liquid chromatography after liquid/liquid extraction with hexane. α-Tocopherol was the major vitamin E congener in all structures. Flowers had a high content of γ-tocopherol. Herbivore-damaged leaves had higher contents of vitamin E than undamaged leaves. Lutein was the major and ß-carotene the second most abundant carotenoid in U. leptophylla. No differences in carotenoid profiles were observed between damaged and undamaged leaves. CONCLUSION: The leaves of U. leptophylla had the highest nutritional value of all analyzed structures; therefore, they might represent a potential source of α-tocopherol, lutein and ß-carotene. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Walnut Oil Reduces Aß Levels and Increases Neurite Length in a Cellular Model of Early Alzheimer Disease.

(1) Background: Mitochondria are the cells' main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer's disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aß) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aß1-40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aß1-40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.

Synthesis of Human Phase I and Phase II Metabolites of Hop (Humulus lupulus) Prenylated Flavonoids.

Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous cyclisation into isoxanthohumol, and subsequently demethylated by gut bacteria. Further combinations of metabolism by hydroxylation, sulfation, and glucuronidation result in an unknown number of isomers. Most investigations involving the analysis of prenylated flavonoids used surrogate or untargeted approaches in metabolite identification, which is prone to errors in absolute identification. Here, we present a synthetic approach to obtaining reference standards for the identification of human xanthohumol metabolites. The synthesised metabolites were subsequently analysed by qTOF LC-MS/MS, and some were matched to a human blood sample obtained after the consumption of 43 mg of micellarised xanthohumol. Additionally, isomers of the reference standards were identified due to their having the same mass fragmentation pattern and different retention times. Overall, the methods unequivocally identified the metabolites of xanthohumol that are present in the blood circulatory system. Lastly, in vitro bioactive testing should be applied using metabolites and not original compounds, as free compounds are scarcely found in human blood.

Effect of two postharvest technologies on the micronutrient profile of cashew kernels from Mozambique.

The economics involved in processing cashew nuts (Anacardium occidentale) might alter micronutrient profiles and concentrations. We analyzed and evaluated carotenoids, tocopherols, tocotrienols, minerals, fatty acids, and amino acids in (1) cashew kernels with testa recovered from nuts dried with and without the apple, and (2) testa-free industrial grade baby butts, splits, and white whole kernels using HPLC, ICP-OES, and GC-MS techniques. The results indicated that drying cashews with the respective apple slightly decreased the concentration of some carotenoids and total fatty and amino acids, but increased the concentration of iron, magnesium, and total tocotrienols compared with the conventionally (sun-) dried kernels. We also found high concentrations of carotenoids in the testa-containing kernels. Among the industrially processed kernel, baby butt grade was associated with lower content of ß-carotene, total tocopherols, and tocotrienols, but with significantly higher concentrations in minerals, fatty acids, and amino acids than in white wholes and split grades. Conventional sun drying of cashew nuts revealed results similar to drying with apples regarding micronutrient concentrations. The high micronutrient content of industrial grade BB is reflected in widespread human consumption and better market value.

Iridoids and polyphenols from chilean Gaultheria spp. berries decrease the glucose uptake in Caco-2 cells after simulated gastrointestinal digestion.

Berries are rich food sources of potentially health-beneficial (poly)phenols. However, they may undergo chemical modifications during gastrointestinal digestion. The effect of simulated gastrointestinal digestion on the content and composition of secondary metabolites from Gaultheria phillyreifolia and G. poeppigii berries was studied. The influence of the digested extracts on the in vitro metabolism and absorption of carbohydrates was evaluated. After simulated digestion, 31 compounds were detected by UHPLC-DAD-MS. The total content of anthocyanins decreased by 98-100%, flavonols by 44-56%, phenylpropanoids by 49-75% and iridoids by 33-45%, the latter showing the highest stability during digestion. Digested extracts inhibited α-glucosidase (IC50 2.8-24.9 µg/mL) and decreased the glucose uptake in Caco-2 cells by 17-28%. Moreover, a decrease in the mRNA expression of glucose transporters SGLT1 (38-92%), GLUT2 (45-96%), GLUT5 (28-89%) and the enzyme sucrase-isomaltase (82-97%) was observed. These results show the effect of simulated gastrointestinal digestion on the content and composition of Gaultheria berries.

Cytotoxicity, cellular uptake, and metabolism to short-chain metabolites of 11'-α-tocomonoenol is similar to RRR-α-tocopherol in HepG2 cells.

Contrary to the major vitamin E congener α-tocopherol, which carries a saturated sidechain, and α-tocotrienol, with a threefold unsaturated sidechain, little is known about the intracellular fate of α-tocomonoenol, a minor vitamin E derivative with a single double bond in C11'-position of the sidechain. We hypothesized that, due to structural similarities, the uptake and metabolism of α-tocomonoenol will resemble that of α-tocopherol. Cytotoxicity, cellular uptake of α-tocomonoenol, α-tocopherol and α-tocotrienol and conversion into the short-chain metabolites αCEHC and αCMBHC were studied in HepG2 cells. α-Tocomonoenol did not show significant effects on cell viability and its uptake was similar to that observed for α-tocopherol and significantly lower than for α-tocotrienol. α-Tocomonoenol was mainly metabolized to αCMBHC in liver cells, but to a lower extent than α-tocotrienol, while α-tocopherol was not metabolized in quantifiable amounts at all. In summary, the similarities in the cytotoxicity, uptake and metabolism of α-tocomonoenol and α-tocopherol suggest that this minor vitamin E congener deserves more attention in future research with regard to its potential vitamin E activity.

Increasing Post-Digestive Solubility of Curcumin Is the Most Successful Strategy to Improve its Oral Bioavailability: A Randomized Cross-Over Trial in Healthy Adults and In Vitro Bioaccessibility Experiments.

SCOPE: Different mechanistic approaches to improve the low oral bioavailability of curcumin have been developed, but not yet directly compared in humans. METHODS AND RESULTS: In a randomized, double-blind, cross-over trial with 12 healthy adults, the 24 h pharmacokinetics of a single dose of 207 mg curcumin is compared from the following formulations: native, liposomes, with turmeric oils, with adjuvants (including piperine), submicron-particles, phytosomes, γ-cyclodextrin complexes, and micelles. No free, but only conjugated curcumin is detected in all subjects. Compared to native curcumin, a significant increase in the area under the plasma concentration-time curve is observed for micellar curcumin (57-fold) and the curcumin-γ-cyclodextrin complex (30-fold) only. In vitro digestive stability, solubility, and micellization efficiency of micellar curcumin (100%, 80%, and 55%) and curcumin-γ-cyclodextrin complex (73%, 33%, and 23%) are higher compared to all other formulations (<72%, <8%, and <4%). The transport efficiencies through Caco-2 cell monolayers of curcumin from the digested mixed-micellar fractions did not differ significantly. CONCLUSION: The improved oral bioavailability of micellar curcumin, and to a lesser extent of γ-cyclodextrin curcumin complexes, appears to be facilitated by increased post-digestive stability and solubility, whereas strategies targeting post-absorptive processes, including inhibition of biotransformation, appear ineffective.

α-Tocomonoenol Is Bioavailable in Mice and May Partly Be Regulated by the Function of the Hepatic α­Tocopherol Transfer Protein.

Tocomonoenols are vitamin E derivatives present in foods with a single double bond at carbon 11' in the sidechain. The α-tocopherol transfer protein (TTP) is required for the maintenance of normal α-tocopherol (αT) concentrations. Its role in the tissue distribution of α-11'-tocomonoenol (αT1) is unknown. We investigated the tissue distribution of αT1 and αT in wild-type (TTP+/+) and TTP knockout (TTP-/-) mice fed diets with either αT or αT1 for two weeks. αT1 was only found in blood, not tissues. αT concentrations in TTP+/+ mice were in the order of adipose tissue > brain > heart > spleen > lungs > kidneys > small intestine > liver. Loss of TTP function depleted αT in all tissues. αT1, contrary to αT, was still present in the blood of TTP-/- mice (16% of αT1 in TTP+/+). Autoclaving and storage at room temperature reduced αT and αT1 in experimental diets. In conclusion, αT1 is bioavailable, reaches the blood in mice, and may not entirely depend on TTP function for secretion into the systemic circulation. However, due to instability of the test compounds in the experimental diets, further in vivo experiments are required to clarify the role of TTP in αT1 secretion. Future research should consider compound stability during autoclaving of rodent feed.

Ascorbic acid, sucrose and olive oil lipids mitigate the inhibitory effects of pectin on the bioaccessibility and Caco-2 cellular uptake of ferulic acid and naringenin.

Whole fruit and vegetable consumption is universally promoted as healthy, to a large extent due to their high contents of phytochemicals, including phenolics and dietary fibre. The major fibre in fruits and vegetables, pectin, however also decreases the bioavailability of phenolics and carotenoids. While ascorbic acid, sucrose and olive oil lipids may increase the bioavailability of various phenolics, their effects in the presence of pectin have not been investigated. This study aimed to evaluate the modulating effects of sucrose (5.0%), ascorbic acid (0.1%) and olive oil (2.5%) on the inhibition by pectin (2.0%) of ferulic acid and naringenin bioaccessibility and Caco-2 cellular uptake. Pectin reduced the bioaccessbility of ferulic acid and naringenin, by 45 and 65%, respectively. Sucrose mitigated the inhibitory effect of pectin and increased naringenin bioaccessbility from 7.9 to 15.0%. When added to digestions with ferulic acid and pectin, sucrose and olive oil totally negated pectin's bioaccessibility inhibition. The Caco-2 cellular uptake of bioaccessible ferulic acid was high (58.3%) and pectin and ascorbic acid together increased it to 85.6%. The Caco-2 cellular uptake of bioaccessible naringenin was also high (47.0%) and pectin increased it to 95.0%. Sucrose and olive oil for ferulic acid and only sucrose for naringenin totally negated the inhibitory effect of pectin on the overall in vitro availability (cellular uptake as percentage of amount of phenolic initially digested). The ameliorating effects of sucrose and olive oil are due to substantially increased bioaccessibility of the phenolics, probably due reduced encapsulation of the phenolics in pectin.

Pharmacokinetics of vitamin E, γ-oryzanol, and ferulic acid in healthy humans after the ingestion of a rice bran-enriched porridge prepared with water or with milk.

PURPOSE: In this study, we investigated the absorption and excretion kinetics of antioxidant dietary phytochemicals (vitamin E, γ-oryzanol, and ferulic acid) in healthy humans after the ingestion of an oatmeal porridge supplemented with rice bran extract (RBE) prepared with water or with whole milk, and we compared it with the intake of an equivalent dose of the rice bran content, in the form of RBE oil. METHODS: Twelve healthy volunteers (6 men and 6 women) orally ingested RBE oil (2 g) or RBE-enriched porridge (35 g, including 2-g RBE) with water or with milk, in a three-armed, crossover trial. Blood and urine samples were collected at baseline and up to 24 h after intake. Vitamin E (α-, ß-, γ-, and δ-tocopherols and tocotrienols), ferulic acid (FA), and γ-oryzanol (ORY) were quantified by HPLC. RESULTS: The ingestion of RBE-fortified oatmeal porridge and RBE oil significantly increased FA concentrations in plasma, showing faster absorption and higher maximum plasma concentrations after the intake of the porridges, irrespective of the addition of water or milk. At least part of the FA could have been hydrolyzed from ORY. However, plasma vitamin E concentrations did not increase from baseline, and no intact FA esters (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, campesteryl ferulate, and ß-sitosteryl ferulate) were detected in plasma or urine with any of the meal treatments. CONCLUSIONS: Rice bran extract-enriched porridge and, to a lesser extent, RBE oil, provide relevant sources of bioaccessible and bioavailable ferulic acid, and could be further developed into functional foods with health potential.

Development and validation of a rapid reversed-phase liquid chromatography method for CnAMP1 peptide quantification in human intestinal cell lines.

Plant foods are rich sources of biologically active peptides that may have a role in the prevention of diseases. Coconut water is a valuable beverage due to its nutrient composition and the presence of bioactive compounds, such as the peptide CnAMP1. It is unknown if CnAMP1 can be absorbed into intestinal cells. We, therefore, aimed to develop and validate a simple reversed-phase liquid chromatographic method to quantify the peptide in Caco-2 and LS180 cell lysates. CnAMP1 standards (1-200 µmol/L) and spiked cell lysates were injected onto a Reprosil-Pur 120 C18-AQ column (4.6 × 250 mm) using acetonitrile:water:trifluoroacetic acid (14.0:85.9:0.1, by volume) as mobile phase in isocratic mode at flow rate of 1 mL/min. The method achieved rapid separation (total run time of 6 min), with linear response, good sensitivity (limit of detection, 8.2 ng; lower limit of quantification, 30.6 ng) and no interfering peaks. Best recoveries (84-96%), accuracies (7.6-14.8%) and precision (1.5-8%) were found for LS180 cell lysates spiked with medium (50 µmol/L) and high (100 µmol/L) amounts of the peptide. Uptake assays detected no peptides in the cell lysates; however, after the first 15-min incubation CnAMP1 underwent partial hydrolysis upon incubation with LS180 cells (29%) and extensive hydrolysis with Caco-2 cells (93%).

α-Tocopherol transfer protein does not regulate the cellular uptake and intracellular distribution of α- and γ-tocopherols and -tocotrienols in cultured liver cells.

Liver cells express a cytosolic α-tocopherol transfer protein (αTTP) with high binding affinity for α-tocopherol (αT) and much lower affinities for the non-αT congeners. The role of αTTP in the intracellular distribution of the different vitamin E forms is currently unknown. We therefore investigated the intracellular localization of αT, γ-tocopherol (γT), α-tocotrienol (αT3), and γ-tocotrienol (γT3) in cultured hepatic cells with and without stable expression of αTTP. We first determined cellular uptake of the four congeners and found the methylation of the chromanol ring and saturation of the sidechain to be important factors, with tocotrienols being taken up more efficiently than tocopherols and the γ-congeners more than the α-congeners, irrespective of the expression of αTTP. This, however, could perhaps also be due to an observed higher stability of tocotrienols, compared to tocopherols, in culture media rather than a higher absorption. We then incubated HepG2 cells and αTTP-expressing HepG2 cells with αT, γT, αT3, or γT3, isolated organelle fractions by density gradient centrifugation, and determined the concentrations of the congeners in the subcellular fractions. All four congeners were primarily associated with the lysosomes, endoplasmic reticulum, and plasma membrane, whereas only αT correlated with mitochondria. Neither the chromanol ring methylation or sidechain saturation, nor the expression of αTTP were important factors for the intracellular distribution of vitamin E. In conclusion, αTTP does not appear to regulate the uptake and intracellular localization of different vitamin E congeners in cultured liver cells.

The Oral Bioavailability of Trans-Resveratrol from a Grapevine-Shoot Extract in Healthy Humans is Significantly Increased by Micellar Solubilization.

SCOPE: Grapevine-shoot extract Vineatrol30 contains abundant resveratrol monomers and oligomers with health-promoting potential. However, the oral bioavailability of these compounds in humans is low (˂1-2%). The aim of this study was to improve the oral bioavailability of resveratrol from vineatrol by micellar solubilization. METHODS AND RESULTS: Twelve healthy volunteers (six women, six men) randomly ingested a single dose of 500 mg vineatrol (30 mg trans-resveratrol, 75 mg trans-ε-viniferin) as native powder or liquid micelles. Plasma and urine were collected at baseline and over 24 h after intake. Resveratrol and viniferin were analyzed by HPLC. The area under the plasma concentration-time curve (AUC) and mean maximum plasma trans-resveratrol concentrations were 5.0-fold and 10.6-fold higher, respectively, after micellar supplementation relative to the native powder. However, no detectable amounts of trans-ε-viniferin were found in either plasma or urine. The transepithelial permeability of trans-resveratrol and trans-ε-viniferin across differentiated Caco-2 monolayers was consistent to the absorbed fractions in vivo. CONCLUSION: The oral bioavailability of trans-resveratrol from the grapevine-shoot extract Vineatrol30 was significantly increased using a liquid micellar formulation, without any treatment-related adverse effects, making it a suitable system for improved supplementation of trans-resveratrol.

The Oral Bioavailability of 8-Prenylnaringenin from Hops (Humulus Lupulus L.) in Healthy Women and Men is Significantly Higher than that of its Positional Isomer 6-Prenylnaringenin in a Randomized Crossover Trial.

SCOPE: Prenylated chalcones and flavonoids from hop (Humulus lupulus L.), such as 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), are investigated for their health beneficial and anticancer activities. We, thus, compare the oral bioavailability and safety of 6-PN and 8-PN in healthy young women and men, and investigated their effects on peripheral blood mononuclear cells (PBMC). METHODS AND RESULTS: A double-blind, placebo-controlled, crossover trial is conducted with 16 healthy volunteers (eight women, eight men) given a single oral dose of 500 mg 6-PN, 8-PN, or placebo in random order. Maximum total concentrations of 6-PN and 8-PN in plasma (Cmax ; 543 and 2834 nmol L-1 ) and their respective area under the plasma concentration-time curve (AUC; 3635 and 15801 nmol L-1 × h) are significantly (5.2- and 4.3-fold) higher for 8-PN than for 6-PN (p Ë‚ 0.05). PBMC for ex vivo experiments are isolated from blood sampled before and 6 h after intake of 6-PN, 8-PN, or placebo. Despite the single-treatment regime and low blood concentrations, both 6-PN and 8-PN increase the survival of PBMC relative to control. CONCLUSION: 8-PN is significantly more bioavailable in healthy humans than its isomer 6-PN. Interestingly, 6-PN, despite being less bioavailable, is similarly effective as 8-PN in enhancing PBMC viability.

Tocopherols, Tocomonoenols, and Tocotrienols in Oils of Costa Rican Palm Fruits: A Comparison between Six Varieties and Chemical versus Mechanical Extraction.

Palm oil is one of the richest sources of tocotrienols and may contain other non-tocopherol vitamin E congeners. The vitamin E profiles of fully ripened fruit mesocarp of three Elaeis guineensis, two Elaeis oleifera, and one hybrid O × G palm fruit genotypes from Costa Rica were analyzed by high-performance liquid chromatography with fluorescence detection and gas chromatography-mass spectrometry after mechanical extraction by a screw press and chemical extraction with hexane. γ-Tocotrienol, α-tocotrienol, and α-tocopherol were the most abundant tocochromanols, while other tocopherols (ß-tocopherol, γ-tocopherol, and δ-tocopherol) and α-tocomonoenol were detected at minor concentrations. Significant differences in vitamin E profiles between genotypes were observed, and the variety E. oleifera Quepos (CB9204) had by far the highest content of total tocotrienols (890 µg/g of oil) and total vitamin E (892 µg/g of oil). Chemical extraction with hexane afforded up to 2.5-fold higher vitamin E yields than screw press extraction. α-Tocomonoenol co-eluted with γ-tocopherol in reversed-phase high-performance liquid chromatography analyses and is a possible source of error in the quantification of γ-tocopherol in foods.

Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice.

Aging represents a major risk factor for the development of neurodegenerative diseases like Alzheimer's disease (AD). As mitochondrial dysfunction plays an important role in brain aging and occurs early in the development of AD, the prevention of mitochondrial dysfunction might help to slow brain aging and the development of neurodegenerative diseases. Rice bran extract (RBE) contains high concentrations of vitamin E congeners and γ-oryzanol. We have previously shown that RBE increased mitochondrial function and protected from mitochondrial dysfunction in vitro and in short-term in vivo feeding studies. To mimic the use of RBE as food additive, we have now investigated the effects of a long-term (6 months) feeding of RBE on survival, behavior and brain mitochondrial function in aged NMRI mice. RBE administration significantly increased survival and performance of aged NMRI mice in the passive avoidance and Y-maze test. Brain mitochondrial dysfunction found in aged mice was ameliorated after RBE administration. Furthermore, data from mRNA and protein expression studies revealed an up-regulation of mitochondrial proteins in RBE-fed mice, suggesting an increase in mitochondrial content which is mediated by a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)-dependent mechanism. Our findings suggest that a long-term treatment with a nutraceutical containing RBE could be useful for slowing down brain aging and thereby delaying or even preventing AD.