Bioaccessibility of carotenoids, tocochromanols, and iron from common bean (Phaseolus vulgaris L.) landraces.

Common beans (Phaseolus vulgaris L.) are among the most important legumes for human nutrition. The aim of the present study was to characterize the composition and in vitro bioaccessibility of tocochromanols, carotenoids, and iron from 14 different landraces and 2 commercial common bean varieties. Phytic acid, dietary fiber, and total (poly)phenolic content were determined as factors that can modify the bioaccessibility of the studied compounds. Two carotenoids were identified, namely lutein (4.6-315 ng/g) and zeaxanthin (12.2-363 ng/g), while two tocochromanols were identified, namely γ-tocopherol (2.62-18.01 µg/g), and δ-tocopherol (0.143-1.44 µg/g). The iron content in the studied samples was in the range of 58.7-144.2 µg/g. The contents of carotenoids, tocochromanols, and iron differed significantly among the studied samples but were within the ranges reported for commercial beans. After simulated gastrointestinal digestion, the average bioaccessibility of carotenoids was 30 %, for tocochromanols 50 %, and 17 % for iron. High variability in the bioaccessible content yielded by the bean varieties was observed. Dietary fiber, phytic acid and total (poly)phenol contents were negatively correlated with the bioaccessibility of carotenoids, while iron bioaccessibility was negatively correlated with the total (poly)phenol content. The principal component analysis indicated that the bioaccessibility of lutein was the main variable involved in class separations. The composition of the food matrix plays an important role in the bioaccessibility of carotenoids, tocochromanols and iron from cooked beans.

Stability and Bioaccessibility of Carotenoids from Sea Buckthorn Pomace Encapsulated in Alginate Hydrogel Beads.

Carotenoids, the natural pigments that confer the bright orange color of sea buckthorn berries, are also associated with several health benefits, such as antioxidant activity and skin and eye protection. Due to their lipophilic nature and localization, carotenoids are largely retained in the sea buckthorn pomace (SBP) resulting from juice production. Carotenoids from SBP (70.03 mg/100 g DW), extracted and characterized by HPLC-PDA, contained zeaxanthin (free and esterified) and beta-carotene as major compounds. The SBP carotenoids-enriched sunflower oil was further encapsulated in Ca-alginate hydrogel beads (98.4% encapsulation efficiency) using ionotropic gelation. The hydrogel beads were characterized by confocal laser scanning microscopy and scanning electron microscopy. Fairly good stability (>64%) of the encapsulated carotenoids in the alginate hydrogel beads during storage (30 days, 4 °C and 25 °C) was found, with zeaxanthin esters being the most stable compounds, for all the experimental conditions. The bioaccessibility of the total carotenoids (INFOGEST protocol) was 42.1 ± 4.6% from hydrated, and, respectively, 40.8 ± 4% from dehydrated SBP alginate hydrogel beads. The addition of yogurt to the dehydrated hydrogel beads had a positive effect on the bioaccessibility of free and esterified zeaxanthin, but not on that of the carotenes. In conclusion, SBP is a valuable source of carotenoids which can be protected by encapsulation in alginate hydrogel beads, thus still retaining a good bioaccessibility.

Bioactivity and Bioavailability of Carotenoids Applied in Human Health: Technological Advances and Innovation.

This article presents a groundbreaking perspective on carotenoids, focusing on their innovative applications and transformative potential in human health and medicine. Research jointly delves deeper into the bioactivity and bioavailability of carotenoids, revealing therapeutic uses and technological advances that have the potential to revolutionize medical treatments. We explore pioneering therapeutic applications in which carotenoids are used to treat chronic diseases such as cancer, cardiovascular disease, and age-related macular degeneration, offering novel protective mechanisms and innovative therapeutic benefits. Our study also shows cutting-edge technological innovations in carotenoid extraction and bioavailability, including the development of supramolecular carriers and advanced nanotechnology, which dramatically improve the absorption and efficacy of these compounds. These technological advances not only ensure consistent quality but also tailor carotenoid therapies to each patient's health needs, paving the way for personalized medicine. By integrating the latest scientific discoveries and innovative techniques, this research provides a prospective perspective on the clinical applications of carotenoids, establishing a new benchmark for future studies in this field. Our findings underscore the importance of optimizing carotenoid extraction, administration, bioactivity, and bioavailability methods to develop more effective, targeted, and personalized treatments, thus offering visionary insight into their potential in modern medical practices.

Comparative pharmacokinetic investigation on crocetin in hyperlipidemia and normal rats after oral administration.

Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication.

Enhancement of dissolution and oral bioavailability by adjusting microenvironment pH in crocetin ternary solid dispersions: Optimization, characterization, in vitro evaluation, and pharmacokinetics.

The most promising active ingredient of Crocus sativus L., crocetin (CCT), has been demonstrated to possess many biological activities. However, only a few studies have been conducted on CCT formulation, especially in oral formulation, mainly due to its insolubility in water, which limits its application for oral administration. This article reports an equilibrium saturation solubility and single-pass intestinal perfusion studies conducted to classify the biopharmaceutics classification system (BCS) of CCT. To enhance in vitro dissolution and in vivo oral bioavailability, ternary solid dispersions of CCT (CCT-SDs) with soluplus (SOL) as hydrophilic carrier and meglumine (MEG) as alkalizer were optimized using response surface methodology (RSM) with central composite design (CCD) experiments. Four different preparation methods were evaluated using the optimal formulation, including solvent evaporation, ball milling, spray drying, and freeze-drying. Prepared formulations were characterized by TG-DSC, FTIR, X-RPD, and SEM; the pharmacokinetic studies were performed in rats after oral administration. The cumulative dissolution rate of CCT-SDs containing SOL and MEG prepared by the ball milling method was 97.1% at 15 min and remained at 95.6% at 480 min, which was significantly higher than that of untreated CCT. The lower crystallinity, smaller particle size, and higher microenvironment pH (pHM) were observed in CCT-SDs prepared by the ball milling method. In vivo absorption of CCT-SDs (Cmax = 52.789 ± 12.441 µg/mL and AUC0-12 = 191.748 ± 35.043 µg/mL·h) was greater than untreated CCT (Cmax = 5.918 ± 1.388 µg/mL and AUC0-12 = 44.309 ± 7.264 µg/mL·h). In conclusion, the current study provides ternary solid dispersion formulation of CCT to increase the in vitro dissolution and in vivo bioavailability, which will benefit the commercial production and future clinical applications of CCT.

Application of E/Z-Isomerization Technology for Enhancing Processing Efficiency, Health-Promoting Effects, and Usability of Carotenoids: A Review and Future Perspectives.

Carotenoids are naturally occurring pigments whose presence in the diet is beneficial to human health. Moreover, they have a wide range of applications in the food, cosmetic, and animal feed industries. As carotenoids contain multiple conjugated double bonds in the molecule, a large number of geometric (E/Z, trans/cis) isomers are theoretically possible. In general, (all-E)-carotenoids are the most predominant geometric isomer in nature, and they have high crystallinity and low solubility in various mediums, resulting in their low processing efficiency and bioavailability. Technological developments for improving the processing efficiency and bioavailability of carotenoids utilizing the Z-isomerization have recently been gaining traction. Namely, Z-isomerization of carotenoids induces a significant change in their physicochemical properties (e.g., solubility and crystallinity), leading to improved processing efficiency and bioavailability as well as several biological activities. For the practical use of isomerization technology for carotenoids, the development of efficient isomerization methods and an acute understanding of the changes in biological activity are required. This review highlights the recent advancements in various conventional and unconventional methods for carotenoid isomerization, such as thermal treatment, light irradiation, microwave irradiation, and catalytic treatment, as well as environment-friendly isomerization methods. Current progress in the improvement of processing efficiency and biological activity utilizing isomerization technology and an application development of carotenoid Z-isomers for the feed industry are also described. In addition, future research challenges in the context of carotenoid isomerization have been elaborated upon.

Effect of an Emulsified Formulation on Vegetable Carotenoid Bioaccessibility.

We investigated the effect of neutral lipids, polar lipids, and an emulsified formulation (EMF) on carotenoid bioaccessibility in an in vitro digestion assay of vegetables. These reagents enhanced carotenoid bioaccessibility. Contrary to our previous report, they also exhibited effects on lutein. Bile extracts/pancreatin concentrations also participated in the bioaccessibility. The EMF, which consisted of lower amounts of oil, had the same effect on lutein as rapeseed oil. These reagents also showed effects in the aging model, with more reduced bile extract/pancreatin concentrations, suggesting that lipids and EMF contributed to carotenoid bioaccessibility in bile/pancreatic juice secretions due to aging and disease.

Oral Bioavailability of Omega-3 Fatty Acids and Carotenoids from the Microalgae Phaeodactylum tricornutum in Healthy Young Adults.

The microalgae Phaeodactylum tricornutum (PT) contains valuable nutrients such as proteins, polyunsaturated omega-3 fatty acids (n-3 PUFA), particularly eicosapentaenoic acid (EPA) and some docosahexaenoic acid (DHA), carotenoids such as fucoxanthin (FX), and beta-glucans, which may confer health benefits. In a randomized intervention trial involving 22 healthy individuals, we administered for two weeks in a crossover manner the whole biomass of PT (5.3 g/day), or fish oil (FO) containing equal amounts of EPA and DHA (together 300 mg/day). In an additional experiment, sea fish at 185 g/week resulting in a similar EPA and DHA intake was administered in nine individuals. We determined the bioavailability of fatty acids and carotenoids and assessed safety parameters. The intake of PT resulted in a similar increase in the n-3 PUFA and EPA content and a decrease in the PUFA n-6:n-3 ratio in plasma. PT intake caused an uptake of FX that is metabolized to fucoxanthinol (FXOH) and amarouciaxanthin A (AxA). No relevant adverse effects occurred following PT consumption. The study shows that PT is a safe and effective source of EPA and FX-and likely other nutrients-and therefore should be considered as a future sustainable food item.

The impact of the physical form of torularhodin on its metabolic fate in the gastrointestinal tract.

Torularhodin is a fungal carotenoid with multiple health benefits. However, the relationship between its physical form and metabolic fate in the gastrointestinal tract (GIT), which is essential to its bioavailability and health efficacy, has rarely been studied. Thus, physical forms of torularhodin including nanoemulsion powder (T-EP), capsules of the T-EP by alginate (T-EPA), and solution in MCT oil (T-oil) were used in the study. T-EP was produced through OSA-starch-mediated torularhodin emulsification and spray drying whereas the T-EPA was alginate-based capsules of the T-EP particles that were entrapped in the network structure of the alginate matrix as observed by scanning electron microscopy (SEM). The oil digestibility in the simulated small intestine was decreased from T-EP (100%), T-oil (60%) to T-EPA (40%), and the bioaccessibilities were 27%, 15% and 12%, respectively. The in vivo study using mice revealed that the content of torularhodin gradually decreased along with the digestion time in both the stomach and small intestine while a significantly higher colonic accumulation was observed in T-EPA compared to T-oil and T-EP. In vitro fecal fermentation showed that propionate (32 mM) was the predominant metabolite produced by torularhodin in the physical form of T-EPA. Thus, the physical form of torularhodin is a significant contributing factor to its GIT metabolic fate, and a health outcome-oriented design of the physical form of torularhodin or other nutraceuticals is beneficial for the development of functional foods with enhanced health benefits.

Bioaccessibility and Cellular Uptake of Carotenoids Extracted from Bactris gasipaes Fruit: Differences between Conventional and Ionic Liquid-Mediated Extraction.

Currently, on an industrial scale, synthetic colorants are used in many fields, as well as those extracted with conventional organic solvents (COSs), leading to several environmental issues. Therefore, we developed a sustainable extraction and purification method mediated by ionic liquids (IL), which is considered an alternative high-performance replacement for COSs. Carotenoids are natural pigments with low bioaccessibility (BCT) and bioavailability (BV) but with huge importance to health. To investigate if the BCT and cellular uptake of the carotenoids are modified by the extraction method, we conducted a comparison assay between both extraction procedures (IL vs. COS). For this, we used the Amazonian fruit Bactris gasipaes, a rich source of pro-vitamin A carotenoids, to obtain the extract, which was emulsified and subjected to an in vitro digestion model followed by the Caco-2 cell absorption assay. The bioaccessibility of carotenoids using IL was better than those using COS (33.25%, and 26.84%, respectively). The cellular uptake of the carotenoids extracted with IL was 1.4-fold higher than those extracted using COS. Thus, IL may be a feasible alternative as extraction solvent in the food industry, replacing COS, since, in this study, no IL was present in the final extract.

Influence of simulated food and oral processing on carotenoid and chlorophyll in vitro bioaccessibility among six spinach genotypes.

Increasing the density of micronutrients and phytochemicals in vegetable foods through plant breeding and processing is of value for consumers. However, the extent to which interactions between genetics and processing (G × P) can be leveraged for green leafy vegetables to improve the delivery of such compounds is unknown. Using spinach as a model, a three-phase in vitro digestion method with and without simulated oral processing (mastication) and coupling to a Caco-2 human intestinal cell culture model was used to determine whether bioaccessibility and intestinal uptake of carotenoids and chlorophylls can be modified from six spinach genotypes, fresh or processed as blanched, sterilized, and juiced products. Carotenoid and chlorophyll bioaccessibility varied significantly with the genotype (p < 0.001) and processing treatment (p < 0.001), with processing having a more profound influence on the bioaccessibility, decreasing micellarization of phytochemicals from juiced (25.8-29.3%), to fresh (19.5-27.9%), to blanched (14.9-20.5%), and sterilized spinach (10.4-13.0%). Oral mastication had a significant influence on the carotenoid bioaccessible content of sterilized spinach (0.3-0.5 µmoles per g DW) as compared to fresh spinach (0.1-0.3 µmoles per g DW), most likely due to the additive effect of thermal processing and mastication on facilitating digestive breakdown of the spinach matrix. Caco-2 accumulation of carotenoid and chlorophyll was modestly but significantly (<0.001) lower in fresh spinach (2.4%) compared to other treatment samples (3.7-4.8%). These results suggest that the genotype, processing treatment, and genotype × processing (G × P) interaction may affect carotenoid and chlorophyll bioaccessibility in spinach and that food processing remains a dominant factor in modulating the bioavailability of these phytochemicals.

Crocins: A comprehensive review of structural characteristics, pharmacokinetics and therapeutic effects.

Crocins, as a kind of water-soluble carotenoid pigment, are a series of ester compounds formed from crocetin and gentibiose or glucose, and mainly distributed among Crocus sativus L. (CSL), Gardenia jasminoides Ellis. (GJE). Crocins exhibit a wide range of pharmacological effects on neurodegeneration, cardiovascular disease, cerebrovascular disease, depression, liver disease, arthritis, tumor, diabetes, etc. This review systematically discussed the pharmacologic study of crocins in the aspect of structural characteristic and pharmacokinetics, and summarized the mechanism of treating disease. It summarized the abundant research of crocins from 1984 to 2020 based on the above aspects, which provide a reference for the deeply development and application of crocins.

Bioanalytical Method Development and Validation Study of Neuroprotective Extract of Kashmiri Saffron Using Ultra-Fast Liquid Chromatography-Tandem Mass Spectrometry (UFLC-MS/MS): In Vivo Pharmacokinetics of Apocarotenoids and Carotenoids.

Kashmir saffron (Crocus sativus L.), also known as Indian saffron, is an important Asian medicinal plant with protective therapeutic applications in brain health. The main bioactive in Kashmir or Indian Saffron (KCS) and its extract (CSE) are apocarotenoids picrocrocin (PIC) and safranal (SAF) with carotenoids, crocetin esters (crocins), and crocetins. The ultra-fast liquid chromatography(UFLC)- photodiode array standardization confirmed the presence of biomarkers PIC, trans-4-GG-crocin (T4C), trans-3-Gg-crocin (T3C), cis-4-GG-crocin (C4C), trans-2-gg-crocin (T2C), trans-crocetin (TCT), and SAF in CSE. This study's objectives were to develop and validate a sensitive and rapid UFLC-tandem mass spectrometry method for PIC and SAF along T4C and TCT in rat plasma with internal standards (IS). The calibration curves were linear (R2 > 0.990), with the lower limit of quantification (LLOQ) as 10 ng/mL. The UFLC-MS/MS assay-based precision (RSD, <15%) and accuracy (RE, -11.03-9.96) on analytical quality control (QC) levels were well within the acceptance criteria with excellent recoveries (91.18-106.86%) in plasma samples. The method was applied to investigate the in vivo pharmacokinetic parameters after oral administration of 40 mg/kg CSE in the rats (n = 6). The active metabolite TCT and T4C, PIC, SAF were quantified for the first time with T3C, C4C, T2C by this validated bioanalytical method, which will be useful for preclinical/clinical trials of CSE as a potential neuroprotective dietary supplement.

Lactucaxanthin protects retinal pigment epithelium from hyperglycemia-regulated hypoxia/ER stress/VEGF pathway mediated angiogenesis in ARPE-19 cell and rat model.

Hyperglycemia mediated perturbations in biochemical pathways induce angiogenesis in diabetic retinopathy (DR) pathogenesis. The present study aimed to investigate the protective effects of lactucaxanthin, a predominant lettuce carotenoid, on hyperglycemia-mediated activation of angiogenesis in vitro and in vivo diabetic model. ARPE-19 cells cultured in 30 mM glucose concentration were treated with lactucaxanthin (5 µM and 10 µM) for 48 h. They were assessed for antioxidant enzyme activity, mitochondrial membrane potential, reactive oxygen species, and cell migration. In the animal experiment, streptozotocin-induced diabetic male Wistar rats were gavaged with lactucaxanthin (200 µM) for 8 weeks. Parameters like animal weight gain, feed intake, water intake, urine output, and fasting blood glucose level were monitored. In both models, lutein-treated groups were considered as a positive control. Hyperglycemia-mediated angiogenic marker expressions in ARPE-19 and retina of diabetic rats were quantified through the western blot technique. Expression of hypoxia, endoplasmic reticulum stress markers, and vascular endothelial growth factor were found to be augmented in the hyperglycemia group compared to control (P < 0.05). Hyperglycemia plays a crucial role in increasing cellular migration and reactive oxygen species besides disrupting tight junction protein. Compared to lutein, lactucaxanthin aids retinal pigment epithelium (RPE) function from hyperglycemia-induced stress conditions via downregulating angiogenesis markers expression. Lactucaxanthin potentiality observed in protecting tight junction protein expression via modulating reactive oxygen species found to conserve RPE integrity. Results demonstrate that lactucaxanthin exhibits robust anti-angiogenic activity for the first time and, therefore, would be useful as an alternative therapy to prevent or delay DR progression.

Modified-release of encapsulated bioactive compounds from annatto seeds produced by optimized ionic gelation techniques.

To compare the encapsulation of annatto extract by external gelation (EG) and internal gelation (IG) and to maximize process yield (% Y), two central composite designs were proposed. Calcium chloride (CaCl2) concentration (0.3-3.5%), alginate to gelling solution ratio (1:2-1:6); acetic acid (CH3COOH) concentration (0.2-5.0%) and alginate to gelling solution ratio (1:2-1:6) were taken as independent variables for EG and IG respectively. Release studies were conducted under different conditions; morphology, particle size, the encapsulation efficiency (EE), and release mechanism were evaluated under optimized conditions. The optimized EG conditions were 0.3% CaCl2 and 1:1.2 alginate to gelling solution ratio, whereas a 0.3% CH3COOH and 1:5 alginate to gelling solution ratio were optimized conditions for IG. When 20% extract was employed, the highest EE was achieved, and the largest release was obtained at a pH 6.5 buffer. The Peppas-Sahlin model presented the best fit to experimental data. Polyphenol release was driven by diffusion, whereas bixin showed anomalous release. These results are promising for application as modulated release agents in food matrices.

Bioaccessibility and cellular uptake by Caco-2 cells of carotenoids and chlorophylls from orange peels: A comparison between conventional and ionic liquid mediated extractions.

Native extracts from orange peels were obtained by a conventional method using acetone and, an alternative method using ionic liquid (1-butyl-3-methylimidazolium chloride ([C4mim]Cl)). The bioaccessibilities and cellular uptakes of carotenoids, esters and chlorophylls were evaluated, since the influence of esterification on bioaccessibility and bioavailability is not well established. For this, the extracts were emulsified, submitted to in vitro simulated digestion model according to the INFOGEST protocol, followed by uptake by Caco-2 cells. Compounds were separated, identified and quantified by HPLC-PDA-MS/MS. After digestion, 22.0% and 26.2% of the total carotenoids and 45.9% and 68.7% of the chlorophylls were bioaccessible from the acetone and [C4mim]Cl extracts, respectively. The bioaccessibilities of xanthophylls and carotenes were significantly higher than those of the mono- and diesters. The uptake by Caco-2 cells varied from 130.2 to 131.9 ng/mg cell protein for total carotenoids and from 243.8 to 234.2 ng/mg cell protein for chlorophylls in the acetone and [C4mim]Cl extracts, respectively. In general, xanthophylls and esters were better absorbed than carotenes.

Synergistic antioxidant effects of phenolic acids and carotenes on H2O2-induced H9c2 cells: Role of cell membrane transporters.

Phenolic acids (caffeic acid, p-coumaric acid,) and carotenes (ß-carotene, lycopene) were mixed in different ratios to investigate antioxidant interactions on H2O2-induced H9c2 cells with ezetimibe (inhibitor of carotenes membrane transporters). Cellular uptake of carotenes, expression of membrane transporters, reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase quinone1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) were analyzed. Results revealed that phenolic acids increased cellular uptake of carotenes and expression of their membrane transporters. Combination groups contained more phenolic acids showed synergistic effects. For example, ß-carotene: caffeic acid = 1:2 significantly suppressed the intracellular ROS (+EZT, 66.34 ±â€¯51.53%) and enhanced the accumulation of nucleus-Nrf2 (+EZT, 30.23 ±â€¯5.30) compared to the groups contained more ß-carotene (+EZT, ROS: 75.48 ±â€¯2.55%, nucleus-Nrf2: 19.48 ±â€¯4.22). This study provided an implication of functional foods formulation and demonstrated that antioxidant synergism may due to the up-regulation of carotenes membrane transporters by phenolic acids.

Bioaccessibility of carotenoids and antioxidant capacity of seed-used pumpkin byproducts powders as affected by particle size and corn oil during in vitro digestion process.

Powders made from seed-used pumpkin flesh (SUPF) are potential sources of carotenoids. In this study, unexplored effects of particle size and corn oil on bioaccessible amounts of carotenoids and antioxidant capacity of SUPF powders during in vitro digestion process were investigated. Overall, total carotenoid relative bioaccessibility (TCRB) of 100 mesh-sized powder (100 MP, 15.46%) was higher than that of 18 mesh-sized powder (18 MP, 12.94%). With the addition of 2% corn oil, TCRB increased 108.35% (18 MP) and 88.55% (100 MP), respectively. Lutein (≥27160 µg/100 g) and ß-carotene (≥5192 µg/100 g) were main carotenoid monomers in SUPF and significantly correlated with DPPH radical scavenging activity of digestive supernatant (p < 0.05). Notably, DPPH radical scavenging activity of 18 MP increased 96.54% with corn oil. These results implied that smaller particle size and oil addition could improve bioaccessible amounts of carotenoids and antioxidant capacity of SUPF powders.

Central Nervous System Migration of Astaxanthin and Adonixanthin Following Their Oral Administration in Cynomolgus Monkeys.

Astaxanthin, which has been shown to have significant antioxidant activity, is rapidly spreading as a health functioning ingredient in the health food and cosmetics sectors worldwide. It is well known that astaxanthin acts on the brain; however, there is little evidence of brain translocation due to the difficulty in identifying astaxanthin in tissues. Therefore, in this study, we investigated the concentrations of astaxanthin and adonixanthin, the latter being a biosynthetic intermediate from ß-carotene to astaxanthin, in the brain after oral administration in primates. Cynomolgus monkeys were orally administered astaxanthin or adonixanthin at a dose of 50 mg/kg for 10 d, through a disposable catheter inserted into the stomach via the nasal passage. Following euthanization, the monkeys' brains and various other organs were collected. The carotenoid content in serum and individual organs was analyzed by high-performance liquid chromatography. Adonixanthin was found to accumulate at a higher concentration than astaxanthin in monkey brain tissues. Also, both astaxanthin and adonixanthin were found to be distributed in the heart, spleen, liver, and kidneys. These findings indicate that astaxanthin and adonixanthin can enter the central nervous system of primates following their oral administration. This provides important evidence for the activity of astaxanthin and adonixanthin on the central nervous system.

Antidementia effects, metabolic profiles and pharmacokinetics of GJ-4, a crocin-rich botanical candidate from Gardeniae fructus.

Crocins, a series of hydrophilic carotenoids that are either mono- or di-glycosyl polyene esters of crocetin extracted from dried saffron stigma or fruits of gardenia, are attracting much attention due to their wide range of pharmacological effects. In our previous study, GJ-4, a mixture of crocin analogues, was obtained and derived from gardenia fruits. Mainly 18 crocin analogues were identified from GJ-4 and found to exhibit neuroprotective effects in in vitro and in vivo models. In this present study, we continue to investigate the therapeutic effects of GJ-4 on learning and memory impairments in a 2VO-induced VaD model, and the potential mechanism. In addition, the metabolic profiles and pharmacokinetic properties of GJ-4 were determined using liquid chromatography-electrospray ionization-mass spectrometry after single and multiple oral doses. All these findings presented here will serve as a solid basis to develop GJ-4 as a new therapeutic agent for dementia.