Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood-retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA-PEG-biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA-PEG-biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA-PEG-biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA-PEG-biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA-PEG-biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.

The ability of nanoparticles from the plant protein zein to protect lutein from light degradation was studied under various conditions. Lutein-zein nanoparticles were synthesized, after zein purification, by anti-solvent precipitation. Particle sizes, ranging from 25 to 75 nm, measured by dynamic light scattering, were tuned by varying zein concentrations in the solvent phase (before anti-solvent precipitation), which was linked to the encapsulation efficiency. However, changes in particle sizes did not result in significant changes in photo-stability. Zein-lutein nanoparticles showed increased photo-stability of lutein when compared to lutein dispersions in water. To further promote the lutein stability, ascorbic acid was used as an antioxidant in the aqueous dispersion. The addition of ascorbic acid to lutein-zein particles resulted in dispersions with similar properties. However, the photo-stability of lutein in dispersions stabilized with ascorbic acid improved significantly compared to samples without ascorbic acid or to pure lutein dispersions (about 25% increased relative stability).

Lutein is a challenging compound to incorporate into food, as it is poorly soluble and unstable in aqueous solutions. In this study, the aim was to prepare stable encapsulates of lutein and lutein esters using feasible and straightforward techniques. Fine suspensions based on polyoxyethylene sorbitan monooleate and medium-chain triglyceride oil micelle-like units with 3.45% lutein esters or 1.9% lutein equivalents provided high encapsulation efficiencies of 79% and 83%, respectively. Lutein encapsulated in fine suspensions showed superior stability, as 86% was retained within the formulation over 250 days at 25 °C in the dark. Under the same storage conditions, only 38% of lutein remained in corresponding formulations. Higher encapsulation efficiencies were achieved with lecithin emulsions, at up to 99.3% for formulations with lutein, and up to 91.4% with lutein esters. In lecithin emulsions that were stored for 250 days, 17% and 80% of lutein and lutein esters, respectively, were retained within the formulations.

Lutein is a kind of vital carotenoid with high safety and significant advantages in biological functions. However, poor water solubility and stability of lutein have limited its application. This study selected different weight ratios of sodium caseinate to acetylated mung bean starch (10:0, 9:1, 7:3, 5:5, 3:7, 1:9, and 0:10) to prepare lutein emulsions, and the microcapsules were produced by spray drying technology. The microstructure, physicochemical properties, and storage stability of microcapsules were investigated. The results show that the emulsion systems were typical non-Newtonian fluids. Lutein microcapsules were light yellow fine powder with smooth and relatively complete particle surface. The increase of sodium caseinate content led to the enhanced emulsion effect of the emulsion and the yield and solubility of microcapsules increased, and wettability and the average particle size became smaller. The encapsulation efficiency of lutein microcapsules ranged from 69.72% to 89.44%. The thermal characteristics analysis showed that the endothermic transition of lutein microcapsules occurred at about 125 °C. The microcapsules with sodium caseinate as single wall material had the worst stability. Thus, it provides a reference for expanding the application of lutein in food, biological, pharmaceutical, and other industries and improving the stability and water dispersion of other lipid-soluble active ingredients.

Lutein is a carotenoid that reduces the risk of some chronic diseases, possibly by altering physical activity behavior. The objective of this study was to conduct a systematic review of studies examining the relationship between lutein status (dietary intake/blood concentration) and physical activity. Peer-reviewed studies published in Medline, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Embase were included if they reported a measure of association between lutein status and physical activity. Seventeen studies met the inclusion criteria. Eleven reported positive associations, three reported mixed results, and three reported no association. Two studies used objective measures of lutein status (blood concentration) and physical activity (accelerometry) and reported positive associations, with correlations of ≥0.36 and differences of ≥57% in physical activity between upper and lower tertiles. Studies using self-report measures reported weaker correlations (r = 0.06 to 0.25), but still more physical activity (18% to ≥600% higher) in those with the highest compared with the lowest lutein status. Higher lutein status may be associated with higher levels of physical activity, which may contribute to a reduced risk of chronic disease.

Epigallocatechin gallate, a major component of green tea polyphenols, protects against the oxidation of fat-soluble antioxidants including lutein. The current study determined the effect of a relatively high but a dietary achievable dose of lutein or lutein plus green tea extract on antioxidant status. Healthy subjects (50-70 years) were randomly assigned to one of two groups (n=20 in each group): (1) a lutein (12 mg/day) supplemented group or (2) a lutein (12 mg/day) plus green tea extract (200 mg/day) supplemented group. After 2 weeks of run-in period consuming less than two servings of lightly colored fruits and vegetables in their diet, each group was treated for 112 days while on their customary regular diets. Plasma carotenoids including lutein, tocopherols, flavanols and ascorbic acid were analyzed by HPLC-UVD and HPLC-electrochemical detector systems; total antioxidant capacity by fluorometry; lipid peroxidation by malondialdehyde using a HPLC system with a fluorescent detector and by total hydroxyoctadecadienoic acids using a GC/MS. Plasma lutein, total carotenoids and ascorbic acid concentrations of subjects in either the lutein group or the lutein plus green tea extract group were significantly increased (P<.05) at 4 weeks and throughout the 16-week study period. However, no significant changes from baseline in any biomarker of overall antioxidant activity or lipid peroxidation of the subjects were seen in either group. Our results indicate that an increase of antioxidant concentrations within a range that could readily be achieved in a healthful diet does not affect in vivo antioxidant status in normal healthy subjects when sufficient amounts of antioxidants already exist.

During the course of proliferative vitreoretinopathy (PVR), the retinal pigment epithelium (RPE) cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF) can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation.

This study was conducted to compare the efficacy of diet supplemented with non-microencapsulated lutein (NL) and microencapsulated lutein (ML) in laying hens. A total of 270 Hy-line Brown laying hens (54 weeks old) were allocated to three groups with six replicates of 15 hens and were adapted to a wheat-soybean meal basal diet for two weeks. Next, the control birds were fed the basal diet, and the test birds were fed the basal diet supplemented with 600 mg/kg NL (12 mg/kg available lutein) or 90.1 mg/kg ML (10 mg/kg available lutein) for 35 days. Supplementation of lutein did not affect the productive performance of laying hens, but improved (P<0.05) the yolk color and red/green value (a*), with eggs from the ML group displaying improved color and a* values from the 15th day of the experimental period. The blue/yellow value (b*) for the yolk showed an increase (P<0.05) through both NL and ML supplements. The yolk color of fried and boiled eggs and a* value of the yolk in fried eggs were improved (P<0.05) only through ML supplemented diet. Both NL and ML supplements resulted in lower (P<0.05) lightness and higher (P<0.05) a* values of yolk in boiled eggs, as well as higher (P<0.05) b* values in fried and boiled eggs. Yolk lutein content in fresh, fried, and boiled eggs was increased (P<0.05) in NL and ML groups with the latter being higher. In conclusion, ML improved yolk pigmentation and lutein retention in laying hens better than NL.

Oxidative stress-induced cell damage and death of the retinal pigmented epithelium (RPE), a polarized monolayer that maintains retinal health and homeostasis, lead to the development of age-related macular degeneration (AMD). Several studies show that the naturally occurring antioxidant Lutein (Lut) can protect RPE cells from oxidative stress. However, the poor solubility and low oral bioavailability limit the potential of Lut as a therapeutic agent. In this study, lutein diglutaric acid (Lut-DG), a prodrug of Lut, was synthesized and its ability to protect human ARPE-19 cells from oxidative stress was tested compared to Lut. Both Lut and Lut-DG significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Moreover, the immunoblotting analysis indicated that both drugs exerted their protective effects by modulating phosphorylated MAPKs (p38, ERK1/2 and SAPK/JNK) and downstream molecules Bax, Bcl-2 and Cytochrome c. In addition, the enzymatic antioxidants glutathione peroxidase (GPx) and catalase (CAT) and non-enzymatic antioxidant glutathione (GSH) were enhanced in cells treated with Lut and Lut-DG. In all cases, Lut-DG was more effective than its parent drug against oxidative stress-induced damage to RPE cells. These findings highlight Lut-DG as a more potent compound than Lut with the protective effects against oxidative stress in RPE cells through the modulation of key MAPKs, apoptotic and antioxidant molecular pathways.

Dietary carotenoids, plant pigments with anti-oxidant properties, accumulate in neural tissue and are often found in lower concentrations among individuals with obesity. Given previous evidence of negative associations between excess adiposity and memory, it is possible that greater carotenoid status may confer neuroprotective effects among persons with overweight or obesity. This study aimed to elucidate relationships between carotenoids assessed in diet, serum, and the macula (macular pigment optical density (MPOD)) and relational memory among adults who are overweight or obese. Adults aged 25-45 years (N = 94) completed a spatial reconstruction task. Task performance was evaluated for accuracy of item placement during reconstruction relative to the location of the item during the study phase. Dietary carotenoids were assessed using 7-day diet records. Serum carotenoids were measured using high-performance liquid chromatography. Hierarchical linear regression analyses were used to determine the relationship between carotenoids and task performance. Although initial correlations indicated that dietary lutein, beta-carotene, and serum beta-carotene were positively associated with memory performance, these relationships were not sustained following adjustment for age, sex, and BMI. Serum lutein remained positively associated with accuracy in object binding and inversely related to misplacement error after controlling for covariates. Macular carotenoids were not related to memory performance. Findings from this study indicate that among the carotenoids evaluated, lutein may play an important role in hippocampal function among adults who are overweight or obese.

Lutein (LUT) is a bioactive food compound found in various vegetables and plays a critical role in the promotion of health and well-being. However, lutein is an unstable molecule which has a very low bioavailability caused by its poor solubility in aqueous media, and is poorly absorbed when administered orally. To enhance the stability, release and bioactivity of lutein, poly-l-lysine (PLL) decorated nanoliposomes (PLL-LUT-NLP) were developed as novel delivery systems for lutein. The mean particle size of PLL-LUT-NLP was found to be in the range 264-367 nm with a low polydispersity index (PDI < 0.4). The zeta potential changed from -38.6 mV in undecorated nanoliposomes to -27.9 mV in PLL-decorated nanoliposomes. Furthermore, the lutein entrapment efficiency (EE%) of PLL-LUT-NLP was found to be highest in nanoliposomes decorated with 0.06% (w/v) PLL. PLL could protect lutein in nanoliposomes from degradation and promote the lutein release from the nanoliposomes in gastrointestinal fluid conditions. Additionally, the PLL-decorated nanoliposomes maintained the antioxidant activity of the lutein, and the antiproliferative activity was more significant than that of undecorated nanoliposomes in inhibiting the proliferation of human tumor cells. These results suggest that PLL-decorated nanoliposomes have potential to be used for efficient delivery of lutein and further improve its bioavailability.

The purpose of this meta-analysis was to evaluate the effects of lutein supplementation on macular pigment optical density (MPOD) in randomized controlled trials involving patients with age-related macular degeneration (AMD). A comprehensive search of the literature was performed in PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan Fang database through December 2018. Nine randomized controlled trials involving 920 eyes (855 with AMD) were included. Meta-analysis suggested that lutein supplementation (10 or 20 mg per day) was associated with an increase in MPOD (mean difference (MD) 0.07; 95% confidence interval (CI) 0.03 to 0.10), visual acuity (MD 0.28; 95%CI 0.06 to 0.50) and contrast sensitivity (MD 0.26; 95%CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment. The available evidence suggests that dietary lutein may be beneficial to AMD patients and the higher dose could make MPOD increase in a shorter time.

Retinal ischemia and oxidative stress lead to neuronal death in many ocular pathologies. Recently, we found that lutein, an oxy-carotenoid, protected the inner retina from ischemia/reperfusion injury. However, it is uncertain whether lutein directly protects retinal ganglion cells (RGCs). Here, an in vitro model of hypoxia and oxidative stress was used to further investigate the neuroprotective role of lutein in RGCs. Cobalt chloride (CoCl(2)) and hydrogen peroxide (H(2)O(2)) were added to a transformed RGC cell line, RGC-5, to induce chemical hypoxia and oxidative stress, respectively. Either lutein or vehicle was added to cultured cells. A higher cell count was observed in the lutein-treated cells compared with the vehicle-treated cells. Our data from this in vitro model revealed that lutein might protect RGC-5 cells from damage when exposed to either CoCl(2)-induced chemical hypoxia or H(2)O(2)-induced oxidative stress. These results suggest that lutein may play a role as a neuroprotectant.

Lutein is a dietary carotenoid of particular nutritional interest as it is preferentially taken up by neural tissues. Often linked with beneficial effects on vision, a broader role for lutein in neuronal differentiation has emerged recently, although the underlying mechanisms for these effects are not yet clear. The purpose of this study was to investigate the effect of lutein on neuronal differentiation and explore the associated underpinning mechanisms. We found that lutein treatment enhanced the differentiation of SH-SY5Y cells, specifically increasing neuronal arborization and expression of the neuronal process filament protein microtubule-associated protein 2. This effect was mediated by the intracellular phosphoinositide-3-kinase (PI3K) signaling pathway. While PI3K activity is a known trigger of neuronal differentiation, more recently it has also been shown to modulate the metabolic state of cells. Our analysis of bioenergetics found that lutein treatment increased glucose consumption, rates of glycolysis and enhanced respiratory activity of mitochondrial complexes. Concomitantly, the generation of reactive oxygen species was increased (consistent with previous reports that reactive oxygen species promote neuronal differentiation), as well as the production of the key metabolic intermediate acetyl-CoA, an essential determinant of epigenetic status in the cell. We suggest that lutein-stimulated neuronal differentiation is mediated by PI3K-dependent modulation of mitochondrial respiration and signaling, and that the consequential metabolic shifts initiate epigenetically dependent transcriptomic reprogramming in support of this morphogenesis. These observations support the potential importance of micronutrients supplementation to neurogenesis, both during normal development and in regenerative repair.

We investigated the antihypertensive effect of lutein on N(G) -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Daily oral administration of L-NAME (40 mg/kg)-induced a rapid progressive increase in mean arterial pressure (MAP). L-NAME significantly increased MAP from the first week compared to that in the control and reached 193.3±9.6 mmHg at the end of treatment. MAP in the lutein groups was dose-dependently lower than that in the L-NAME group. Similar results were observed for systolic and diastolic blood pressure of L-NAME-induced hypertensive rats. The control group showed little change in heart rate for 3 weeks, whereas L-NAME significantly reduced heart rate from 434±26 to 376±33 beats/min. Lutein (2 mg/kg) significantly prevented the reduced heart rate induced by L-NAME. L-NAME caused hypertrophy of heart and kidney, and increased plasma lipid peroxidation four-fold but significantly reduced plasma nitrite and glutathione concentrations, which were significantly prevented by lutein in a dose-dependent manner. These findings suggest that lutein affords significant antihypertensive and antioxidant effects against L-NAME-induced hypertension in rats.

To test the hypothesis that neonatal supplementation with lutein in the first hours of life reduces neonatal oxidative stress (OS) in the immediate postpartum period.

Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration. There is currently no effective treatment for retinitis pigmentosa. Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration, the role of lutein alone remains unclear. In this study, we administered intragastric lutein to Pde6brd10 model mice, which display degeneration of retinal photoreceptors, on postnatal days 17 (P17) to P25, when rod apoptosis reaches peak. Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control. Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells, in line with an increased survival rate of photoreceptors. Functionally, lutein improved visual behavior, visual acuity, and retinal electroretinogram responses in Pde6brd10 mice. Mechanistically, lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells. The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects. This study was approved by the Laboratory Animal Ethics Committee of Jinan University (approval No. LACUC-20181217-02) on December 17, 2018.

This study was conducted to investigate the effects of lutein alone or in combination with vitamin C on the antioxidant defense system in rats. A total of 18 eight-week-old male Sprague Dawley (SD) rats were randomly assigned to three groups for 4 weeks: control (CON), lutein (LUT, 50 mg lutein/kg BW) and lutein plus vitamin C (LVC, 50 mg lutein/kg BW+1,000 mg vitamin C/kg BW). No differences in body weight, relative live weight or plasma biochemical profiles were observed among treatment groups. In the hepatic antioxidant defense systems, the mRNA expression of superoxide dismutase (SOD) in the LUT and LVC groups was significantly (P<0.05) higher than that in the CON group, whereas the mRNA level of glutathione peroxidase (GPX), catalase (CAT) and glutathione S-transferase (GST) was not affected by the administration of antioxidants. SOD and GST activities in the LUT and LVC groups were significantly higher (P<0.05) than those in the CON group, whereas GPX, CAT and lipid peroxidation did not differ among groups. In addition, the LVC group showed a significant (P<0.05) increase in plasma and hepatic total antioxidant power (TAP) relative to the CON group. Overall, administration of lutein in combination with vitamin C improved the status of the total antioxidant defense system in SD rats.

Osteoarthritis is an inflammatory disorder associated with oxidative stress and apoptosis leading to cartilage destruction and impairment of cartilage formation. In the present study, we studied the protective effect of lutein against monosodium iodoacetate (MIA)-induced osteoarthritis in primary chondrocyte cells.

Declining immune function poses an important clinical challenge worldwide and supplementation with natural products that possessing immune enhancing properties is a promising approach for preventing or delaying immune function decline. Cocoons from yellow silkworms are a significant source of lutein, and this unexplored silk extract could be a viable alternative source for dietary lutein. This study assessed immunomodulatory activities of the silk lutein extract. Female BALB/c mice orally received lutein, either as silk or marigold extracts (10 or 20 mg/kg daily), or vehicle only (1% tween 80 in PBS pH 7.4) for 4 weeks. Natural killer (NK) cell activity, specific antibody production, lymphocyte subpopulations, mitogen-induced lymphocyte proliferation, and cytokine production were examined.