Lutein and Zeaxanthin Supplementation Improves Dynamic Visual and Cognitive Performance in Children: A Randomized, Double-Blind, Parallel, Placebo-Controlled Study.

INTRODUCTION: Supplementation with dietary neuro-pigments lutein (L) and zeaxanthin (Z) has been shown to improve many aspects of visual and cognitive function in adults. In this study, we tested whether a similar intervention could improve such outcomes in preadolescent children. METHODS: Sixty children (age range 5-12 years) were randomized in a 2:1 ratio in this double-blind, placebo-controlled clinical trial. Subjects were supplemented with gummies containing either a combination of 10 mg lutein and 2 mg zeaxanthin (LZ) or placebo for 180 days. Macular pigment optical density (MPOD) was the primary endpoint. The secondary endpoints included serum levels of L and Z, and brain-derived neurotrophic factor (BDNF), critical flicker fusion (CFF), eye strain and fatigue using visual analogue scales (VAS), Children's Sleep Habits Questionnaire-Abbreviated (CSHQ-A), and Creyos Health cognitive domains like attention, focus/concentration, episodic memory and learning, visuospatial working memory, and visuospatial processing speed. Safety was assessed throughout the study on the basis of physical examination, vital signs, clinical laboratory tests, and monitoring of adverse events. RESULTS: The LZ group showed significant increases in MPOD at all visits post-supplementation, with significant increases as early as day 42 compared to placebo. The LZ group showed significant increases in serum lutein levels, reduced eye strain and fatigue, and improved cognitive performance (focus, episodic memory and learning, visuospatial working memory) at days 90 and 180 compared to placebo. Further, the LZ group showed significant increases in processing speed (CFF), attention, visuospatial processing, and serum Z and BDNF levels on day 180 compared to placebo. No safety concerns were observed. CONCLUSIONS: Supplementing LZ resulted in increased MPOD levels, along with increased serum levels of L, Z, and BDNF. These changes were associated with improved visual and cognitive performances and reduction in eye strain and eye fatigue in the children receiving LZ gummies. The investigational product was safe and well tolerated. TRIAL REGISTRATION: http://ctri.nic.in/ Identifier CTRI/2022/05/042364.

Uteroovarian pathway for embryo-empowered maintenance of the corpus luteum in farm animals.

The first luteal response to pregnancy in farm animals at 12-18 days after ovulation involves maintenance of the corpus luteum (CL) if pregnancy has occurred. In most common farm species, regression of the CL results from production of a luteolysin (PGF2α) by the nongravid uterus, and maintenance of the CL involves the production of an antiluteolysin (PGE2) by the gravid uterus and conceptus. The proximal component of a unilateral pathway from a uterine horn to the adjacent CL for transport of PGF2α and PGE2 is the uterine venous and lymphatic vessels and the distal component is the ovarian artery. The mechanisms for venolymphatic arterial transport of PGF2α and PGE2 from a uterine horn to the adjacent CL ovary and transfer of each prostaglandin through the walls of the uteroovarian vein and ovarian artery occur by similar mechanisms probably as a consequence of similarities in molecular structure between the two prostaglandins. Reported conclusions or interpretations during the first luteal response to pregnancy in sows and ewes are that PGE2 increases in concentration in the uteroovarian vein and ovarian artery and counteracts the negative effect of PGF2α on the CL. In cows, treatment with PGE2 increases circulating progesterone concentrations and prevents spontaneous luteolysis and luteolysis induced by estradiol, an intrauterine device, or PGF2α. The prevailing acceptance that interferon tau is the primary factor for maintaining the CL during early pregnancy in ruminants will likely become tempered by the increasing reports on PGE2.

The presence of free palmitic acid modulates the effects of lutein on structural and dynamic properties of lipid membranes.

Free fatty acids, like palmitic acid (PA), and xanthophyll pigments, like lutein (LUT) are the natural membrane compounds in plants. To study the effect of PA on LUT and their organization, a model membrane of 1,2-dimyristoyl-sn-glycerol-3-phosphocholine (DMPC) enriched with 2 mol% PA and 1 mol% LUT was formed. Molecular mechanisms underlying the interaction between these two compounds were examined with application of molecular spectroscopy techniques, e.g., visible spectroscopy, electron paramagnetic resonance and Fourier transform infrared. We determined the monomeric/dimeric organization of LUT in the membrane. We proved that the presence of PA in the lipid phase facilitated and stabilized the formation of LUT structures in the membrane. Lutein with PA did not form strong molecular aggregates like H- and J-structures. We presented the simplified model membrane that could be a suitable representation of the physiological process of de-esterification of PA from LUT appearing in natural biomembranes in humans.

The role of carotenoids in bone health-A narrative review.

Osteoporosis constitutes a serious challenge for public health. Dietary patterns belong to important, modifiable risk factors of this disease. Therefore, what and in what quantities we consume on a daily basis are extremely relevant. It is commonly known that bone health is positively affected by vitamins (e.g., vitamin D and vitamin K) as well as mineral components (e.g., calcium and magnesium). However, the human diet consists of many other groups of compounds that exhibit a potential antiosteoporotic and supporting bone-building effect. These dietary components include carotenoids. This paper presents a broad review of studies on the influence of particular carotenoids (ß-carotene, lutein, zeaxanthin, ß-cryptoxanthin, and lycopene) on bones. The paper discusses up-to-date in vitro experiments and research on animal models and presents how the results translate into clinical effect in humans.

Luteal tissue characteristics of Morada Nova ewes with hCG application 7.5 days after the end of estrus synchronization protocol in the breeding season.

Results with the use of hCG after synchronization protocol are still inconsistent, which may vary according to breed, season, day of application and dose of the drug used. The aim of the present study was to evaluate the functionality of luteal tissue and ovarian perfusion after hCG treatment during early luteal phase. Estrus-synchronized ewes were randomly assigned to receive i.m. injection of 300 IU of hCG (G-hCG; n = 40) or 1 mL of saline (G-Control; n = 32) on Day 7.5 after progesterone withdrawal. Ultrasonographic evaluations of the ovaries and ovarian and iliac arteries were performed on Days 7.5, 10.5, 13.5, and 21.5. The accessory corpus luteum (aCL) formation rate was 52.5% for G-hCG. There was interaction (p > 0.05) for treatment (G-hCG and G-Control), days (7.5, 10.5, 13.5 and 21.5) and PD (Pregnant and Non-pregnant) for the variables of biometric characteristics of the corpus luteum B-Mode and Color Doppler on days 7.5, 10.5, 13.5 and 21.5. There was no difference (p > 0.05) for pregnancy rates and mean fetuses per ewe between the treatment groups. It is concluded that the application of hCG 7.5 days after the hormonal protocol in Morada Nova ewes in a breeding season is efficient in inducing aCL formation and increasing luteal tissue biometry. However, there was no effect on pregnancy rate.

MWCNTs Alleviated saline-alkali stress by optimizing photosynthesis and sucrose metabolism in rice seedling.

Saline and alkali stress affects the growth and development, survival rate, and final yield of rice, while new nano materials can have a positive effect on rice growth. In order to investing the effects of carboxymethyl multi walled carbon nanotubes (MWCNTs) on the growth and development of rice seedlings under salt alkali stress, rice seedlings were cultured using rice variety "Songjing 3" using nutrient solution water culture method. The effects of MWCNTs on water absorption capacity, leaf photosynthesis, and sucrose metabolism of rice seedlings under 50 mmol/L saline-alkali stress (1NaCl: 9Na2SO4: 9NaHCO3: 1Na2CO3) conditions were investigated. The results showed that MWCNTs can improve the water use ability of roots and leaves, especially the water absorption ability of roots, which provides a guarantee for the improvement of rice biomass and the enhancement of leaf photosynthetic capacity under adverse conditions. After treatment with MWCNTs, the photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (Tr) of leaves increased significantly, and the photochemical quenching value (qP), photochemical quantum efficiency value (Fv/Fm), and electron transfer rate value (ETR) of chlorophyll fluorescence parameters increased significantly, which is beneficial to the improvement of the PSII photosynthetic system. MWCNTs treatment promoted the increase of photosynthetic pigment content in leaves under salt and alkali stress, improved the ratio of Chla and Chlb parameters, increased the activities of key photosynthetic enzymes (RUBPCase and PEPCase) in leaves, increased the value of total lutein cycle pool (VAZ), and significantly enhanced the deepoxidation effect of lutein cycle (DEPS), which can effectively alleviate the stomatal and non stomatal constraints on leaf photosynthesis caused by salt and alkali stress. MWCNTs treatment significantly enhanced the activities of sucrose phosphate synthase (SPS) and sucrose synthase (SS) under salt and alkali stress, and decreased the activities of soluble acid invertase (SAInv) and alkaline/neutral invertase (A/N-Inv), indicating that MWCNTs promoted sucrose synthesis while inhibiting sucrose decomposition, thereby promoting sucrose accumulation in rice leaves. This study can provide theoretical and experimental basis for the application of MWCNTs to the production of rice under salt and alkali stress, and can find a new way for rice production in saline and alkaline lands.

The Antioxidant and Anti-Inflammatory Effects of the Main Carotenoids from Tomatoes via Nrf2 and NF-κB Signaling Pathways.

Oxidative stress and inflammation are crucial factors in the development of cardiovascular diseases. In previous research, the oxidative stress and inflammation models have frequently been explored independently. In the current study, we investigated the antioxidant and anti-inflammatory effects of tomato extract and its two main carotenoids (lutein and lycopene) with various concentrations using a rat cardiomyocyte model of co-existing oxidative stress and persistent chronic inflammation. It was discovered that the antioxidant effects of 0.5-5 µM lutein, 0.5-5 µM lycopene, and 50-200 µg/mL tomato extract increased in a dose-dependent manner. However, the pro-oxidation effects emerged by measuring the antioxidant-related indices, including the levels of ROS, SOD, and GPX in H9c2 cells as concentrations exceeded those mentioned above. The anti-inflammatory effects of lutein, lycopene, and tomato extract were simultaneously strengthened with higher concentrations, potentially due to the suppression of the NF-κB signaling pathway. Furthermore, high concentrations of lutein, lycopene, and tomato extract potentially regulated Nrf2/HO-1 and NF-κB signaling pathways dependent on TGF-1ß and IL-10 to demonstrate high concentrations of pro-oxidation and anti-inflammation effects. Our findings indicate that the dose-effect regulatory mechanisms of antioxidant and anti-inflammatory properties among lutein, lycopene, and tomato extract will be advantageous in developing more effective therapeutic strategies to prevent cardiovascular diseases.

Assessment of the therapeutic potential of lutein and beta-carotene nanodispersions in a rat model of fibromyalgia.

Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and cognitive impairment. Despite the availability of various treatment options, FM remains a challenging condition to manage. In the present study, we investigated the efficacy of formulated nanodispersions of lutein and beta-carotene in treating FM-related symptoms induced by reserpine in female Wistar rats. Several techniques have been implemented to assess this efficacy at various levels, including biochemical, bioelectrical, and behavioral. Namely, oxidative stress markers, monoamine levels, electrocorticography, pain threshold test, and open field test were conducted on control, FM-induced, and FM-treated groups of animals. Our results provided compelling evidence for the efficacy of carotenoid nanodispersions in treating FM-related symptoms. Specifically, we found that the dual action of the nanodispersion, as both antioxidant and antidepressant, accounted for their beneficial effects in treating FM. With further investigation, nano-carotenoids and particularly nano-lutein could potentially become an effective alternative treatment for patients with FM who do not respond to current treatment options.

Lutein suppresses ferroptosis of cardiac microvascular endothelial cells via positive regulation of IRF in cardiac hypertrophy.

Cardiac microvascular dysfunction contributes to cardiac hypertrophy (CH) and can progress to heart failure. Lutein is a carotenoid with various pharmacological properties, such as anti-apoptotic, anti-inflammatory, and antioxidant effects. Limited research has been conducted on the effects of lutein on pressure overload-induced CH. Studies have shown that CH is accompanied by ferroptosis in the cardiac microvascular endothelial cells (CMECs). This study aimed to investigate the effect of lutein on ferroptosis of CMECs in CH. The transcription factor interferon regulatory factor (IRF) is associated with immune system function, tumor suppression, and apoptosis. The results of this study suggested that pressure overload primarily inhibits IRF expression, resulting in endothelial ferroptosis. Administration of lutein increased the expression of IRF, providing protection to endothelial cells during pressure overload. IRF silencing downregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, leading to the induction of ferroptosis in CMECs. Lutein supplementation suppressed endothelial ferroptosis by upregulating IRF. These data suggest that IRF may function as a transcription factor for SLC7A11 and that lutein represses ferroptosis in CMECs by upregulating IRF expression. Therefore, targeting IRF may be a promising therapeutic strategy for effective cardioprotection in patients with CH and heart failure.

Biomimetic nanoparticles loaded lutein functionalized by macrophage membrane for targeted amelioration pressure overload-induced cardiac fibrosis.

Lutein is a strong antioxidant with anti-inflammatory, anti-oxidative and cardioprotective effects and could be a promising candidate for the treatment of hypertensive heart disease (HHD), but is not clinically appealing because of its low oral bioavailability and main distribution in the eyes. To address this, a biomimetic drug delivery system-MMLNPs was established by coating macrophage membranes (MMs) onto lutein-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (LNPs). This study characterized the physical properties of biomimetic nanoparticles and examined the targeting capability, therapeutic effects and mechanism, and biosecurity of administering them for cardiac fibrosis therapy in the transverse aortic constriction (TAC) model and in vitro. Transmission electron microscope mapping and dynamic light scattering analysis proved that MMLNPs were spherical nanoparticles camouflaged by a layer of cell membrane and had negative zeta potential. Confocal laser scanning microscopy and flow cytometry analysis showed that MMs on the biomimetic nanoparticles hindered the phagocytosis of macrophages and facilitated the targeting of activated endothelial cells. Ex vivo fluorescence imaging experiments demonstrated the targeting of biomimetic nanoparticles to the injured heart. EdU assay indicated that MMLNPs have the same potential to inhibit angiotensin (Ang) II-induced cardiac fibroblast proliferation as free lutein. Furthermore, echocardiography showed that MMLNPs improved cardiac function and structure, and Masson staining and western blotting showed that MMLNPs ameliorated cardiac fibrosis. We found MMLNPs inhibited the interleukin (IL)-11/ERK signaling pathway which was up-regulated in the TAC model compared to the sham-operated mouse. Biochemical testing and hematoxylin and eosin staining proved that the long-term use of MMLNPs lacked biological toxicity. Collectively, MMLNPs might be a promising nanodrug delivery approach to attenuate pressure overload (PO)-induced cardiac fibrosis.

Enhancing stability of liposomes using high molecular weight chitosan to promote antioxidative stress effects and lipid-lowering activity of encapsulated lutein in vivo and in vitro.

Lutein is an antioxidant with multiple beneficial functions. However, its therapeutic potential is hampered by its low water solubility and bioavailability. The goal of this study is to compare the stability of lutein-loaded liposomes (Lu-lip) and low (LC)/high molecular weight (HC) chitosan-coated Lu-lip, along with their antioxidant capacity using H2O2-induced HepG2 cells and their lipid-lowering activity using high-fat diet mice. Both LC and HC reduced the lutein degradation rate by 17.5 % and 26.72 % in a challenging environment at pH 6 and T = 4 °C. Compared to LC, the HC coating improved the size- and zeta-potential-stability of Lu-lip at 5 < pH < 7, with the best performance at pH 6. The HC coating prolonged the lutein release profile, increased the cellular uptake of Lu-lip, and reduced the reactive oxygen species (ROS) levels and the H2O2-induced necrotic cell ratios by increasing the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Animal experiments have shown that oral administration of LC and HC coated Lu-lip can significantly reduce body weight levels, total triglycerides (TG), total cholesterol (TC), and non-high-density lipoprotein (n-HDL-C) in high-fat diet mice while significantly increasing the levels of CAT, SOD and GSH-Px in the liver of mice. LC and HC coated Lu-lip can reduce fat accumulation in the liver and epididymal adipose tissue.

Lutein and zeaxanthin - radio- and chemoprotective properties. Mechanism and possible use.

Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum light absorbance, including UV. This property, and fact, that these xanthophylls are accumulated by human eye's macula, leads to eye's protective functions of them including protection from age-related macular degeneration (AMD). Also, antioxidative features of lutein and zeaxanthin are boosting overall health of human body. Numerous studies proves anti-inflammatory and protective attributes of these compounds, based on many, different mechanisms. One of them is regulating redox potential in cells, and impact on expression of linked genes. In preventing of eye diseases, an important gene that is regulated by lutein and zeaxanthin is the Nrf2 gene, whose increased activity leads to optimizing the cellular response to reactive oxygen species (ROS) and preventing related diseases. Other research confirms antiproliferative properties of mentioned compounds in case of certain human cancer cell lines. There are e.g.: HepG2 (hepatitis cancer), MCF-7 (breast cancer), which treated in vitro with lutein solution showed reduction of cell growth. Lutein alone, during in vivo studies conducted on mice, exhibited also radioprotective properties, positively affecting the vitality of animals. Lutein provides also increasing of tolerance to UV radiation, reducing inflammatory processes in the skin and preventing oncogenesis. Low intake of lutein and zeaxanthin, associated with "western diet", rich in simple carbohydrates and processed food, common in developed countries, including Poland, is linked with diabetes and obesity incidence. Assuming, lutein and zeaxanthin significantly affect the well-being of the human body, and their appropriate amount in diet can help reduce risk of many diseases. For supplementation, the optimized dosage of these xanthophylls includes doses of 10 mg for lutein and 2 mg for zeaxanthin, and it is recommended to consume along with fats or meals rich in fats.

Antioxidant, Antiviral, and Anti-Inflammatory Activities of Lutein-Enriched Extract of Tetraselmis Species.

Microalgae are proposed to have powerful applications for human health in the pharmaceutical and food industries. Tetraselmis species (sp.), which are green microalgae, were identified as a source of broad-spectrum health-promoting biological activities. However, the bioactivity of these species has not been elucidated. We aimed to confirm the antioxidant, antiviral, and anti-inflammatory effects of Tetraselmis sp. extract (TEE). TEE showed 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical and hydrogen peroxide scavenging activities and reduced plaque formation in Vero E6 cells infected with vaccinia virus. TEE treatment also significantly inhibited nitric oxide (NO) production and improved cell viability in lipopolysaccharide (LPS)-induced RAW264.7 cells. These anti-inflammatory effects were further analyzed in LPS-induced RAW 264.7 cells and the zebrafish model. Further, TEE reduced induced NO synthase expression and proinflammatory cytokine release, including tumor necrosis factor-α, interleukin-6, and interleukin-1ß, through MAPKs and NF-κB-dependent mechanisms. Further analysis revealed that TEE increased the survival rate and reduced cell death and NO production in an LPS-stimulated zebrafish model. Further, high-performance liquid chromatography revealed a strong presence of the carotenoid lutein in TEE. Overall, the results suggest that lutein-enriched TEE may be a potent antioxidant, antiviral, and anti-inflammatory agent that could be sustainably utilized in industrial applications.

Effects of Long-Chain Polyunsaturated Fatty Acids in Combination with Lutein and Zeaxanthin on Episodic Memory in Healthy Older Adults.

Arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), which are long-chain polyunsaturated fatty acids (LCPUFAs), as well as lutein (L) and zeaxanthin (Z), can potentially improve brain function. However, the effect of a combination of these components (LCPUFAs + LZ) on memory function in healthy older individuals remains unclear. This study aimed to determine if LCPUFAs + LZ-supplemented food could improve memory function. Exploratory and confirmatory trials (Trials 1 and 2, respectively) were conducted in healthy older Japanese individuals with memory complaints. We conducted randomized, double-blind, placebo-controlled, parallel-group trials. Participants were randomly allocated to two groups: placebo or LCPUFAs + LZ. LCPUFAs + LZ participants were provided with supplements containing ARA, DHA, EPA, L, and Z for 24 weeks in Trial 1 and 12 weeks in Trial 2. Memory functions were evaluated using Cognitrax before and after each trial. Combined analyses were performed for subgroups of participants with cognitive decline in Trials 1 and 2. The results showed that supplementation with LCPUFAs + LZ did not significantly affect memory function in healthy, non-demented, older individuals with memory complaints whereas it improved memory function in healthy, non-demented, older individuals with cognitive decline.

Xanthophyll-Rich Extract of Phaeodactylum tricornutum Bohlin as New Photoprotective Cosmeceutical Agent: Safety and Efficacy Assessment on In Vitro Reconstructed Human Epidermis Model.

The nutritional and health properties of algae make them perfect functional ingredients for nutraceutical and cosmeceutical applications. In this study, the Phaeodactylum tricornutum Bohlin (Phaeodactylaceae), a pleiomorphic diatom commonly found in marine ecosystems, was investigated. The in vitro culture conditions used favoured the fusiform morphotype, characterized by a high accumulation of neutral lipids, as detected by fluorescence microscopy after BODIPY staining. These data were confirmed by HPLC-DAD-APCI-MS/MS analyses carried out on the ethanolic extract (PTE), which showed a high content of xanthophylls (98.99%), and in particular of fucoxanthin (Fx, 6.67 g/100 g PTE). The antioxidant activity (ORAC, FRAP, TEAC and ß-carotene bleaching) and photostability of PTE and Fx against UVA and UVB rays were firstly evaluated by in vitro cell-free assays. After this, phototoxicity and photoprotective studies were carried out on in vitro reconstructed human epidermidis models. Results demonstrated that PTE (0.1% Fx) and 0.1% Fx, both photostable, significantly (p < 0.05) reduce oxidative and inflammatory stress markers (ROS, NO and IL-1α), as well as cytotoxicity and sunburn cells induced by UVA and UVB doses simulating the solar radiation, with an excellent safety profile. However, PTE proved to be more effective than Fx, suggesting its effective and safe use in broad-spectrum sunscreens.

Lutein targeting orbital fibroblasts attenuates fibrotic and inflammatory effects in thyroid-associated ophthalmopathy.

Lutein (LU) is a carotenoid that has recently been implicated in multiple roles in fibrosis, inflammation, and oxidative stress. Thyroid-associated ophthalmopathy (TAO) is particularly relevant to these pathological changes. We thus aim to probe the potential therapeutic effects of TAO in an in vitro model. We used LU pre-treating OFs derived from patients with TAO or not, then treated with TGF-ß1(or IL-1ß)to induce fibrosis (or inflammation). We analyzed the different expressions of related genes and proteins, and the molecular mechanism pathway on TAO OFs was screened by RNA sequencing, which is identified in vitro. We found that LU attenuates fibrotic and inflammatory effects in TAO. LU inhibited ACTA2, COL1A1, FN1, and CTGF mRNA expression and suppressed α-SMA, and FN1 protein expression induced by TGF-ß1. Besides, LU suppressed OFs migration. Besides, it is shown that LU suppressed inflammation-related genes, such as IL-6, IL-8, CXCL1, and MCP-1. Moreover, LU inhibited oxidative stress induced by IL-1ß, which is analyzed by DHE fluorescent probe staining. RNA sequencing suggested ERK/AP-1 pathway may be the molecular mechanism of LU protective effect on TAO, which is identified by RT-qPCR and western-blot. In summary, this study provides the first evidence that LU significantly attenuates the pathogenic manifestations of TAO by inhibiting the expression of fibrotic and inflammation-related genes and ROS produced by OFs. These data suggested that LU may be a potential medicine for TAO.

Consumption of Nutritionally Enriched Hen Eggs Enhances Endothelium-Dependent Vasodilation via Cyclooxygenase Metabolites in Healthy Young People-A Randomized Study.

OBJECTIVE: The present study aimed to evaluate the effects of enriched hen egg consumption on endothelium-dependent vasodilation (EDV) and the role of cyclooxygenases in EDV in the microcirculation of young healthy individuals. This study hypothesizes that Nutri4 eggs will improve endothelial function, which will be manifested by changes in microcirculatory flow measured by a laser Doppler flowmeter (LDF) during reactive hyperemia in response to vascular occlusion, in which n-3 PUFA plays an important role as well as its degradation pathway by cyclooxygenases. MATERIALS AND METHODS: Participants consumed three eggs per day for three weeks: The control group (CTRL, n = 14) consumed regular hen eggs (approximately 0.330 mg of lutein, 1.785 mg of vitamin E, 0.054 mg of selenium and 438 mg of n-3 PUFAs daily) and Nutri4 group (n = 20) consumed enriched eggs (approximately 1.85 mg of lutein, 0.06 mg of selenium, 3.29 mg of vitamin E, and 1026 mg of n-3 PUFAs daily). Skin microvascular blood flow in response to EDV (post-occlusive reactive hyperemia (PORH) and iontophoresis of acetylcholine (AChID)) and sodium nitroprusside (SNPID; endothelium-independent) was assessed by laser Doppler flowmetry before and after dietary protocol and in a separate group of participants who were administered perorally 100 mg of indomethacin before microvascular response assessment. Arterial blood pressure, heart rate, serum lipid, and liver enzymes, anthropometric measurements, protein expression of cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), neuronal nitric oxide synthases (nNOS), inducible nitric oxide synthases (iNOS), and endothelial nitric oxide synthases (eNOS) were measured before and after dietary protocol. RESULTS: PORH and AChID were significantly enhanced, and SNPID remained unchanged in the Nutri4 group, while none was changed in the CTRL following a respective diet. PORH decreased after administration of indomethacin in Nutri4 after dietary protocol. Protein expression of COX-2 was significantly higher in the Nutri4 group compared to the CTRL after the dietary protocol. CONCLUSION: Consumption of enriched eggs improves microvascular EDV in healthy young subjects. Results suggest an element of n-3 PUFAs metabolites via the cyclooxygenases pathway in enhanced reactive hyperemia.

Lutein inhibits tumor progression through the ATR/Chk1/p53 signaling pathway in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related death. In particular, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Due to tumor resistance and the toxicity of chemotherapeutic agents, it is increasingly critical to discover novel, potent antitumorigenic drugs for treating NSCLC. Lutein, a carotenoid, has been reported to exert toxic effects on cells in several tumor types. However, the detailed functions and underlying mechanisms of lutein in NSCLC remain elusive. The present study showed that lutein significantly and dose-dependently inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in NSCLC cells. RNA-sequencing analysis revealed that the p53 signaling pathway was the most significantly upregulated in lutein-treated A549 cells. Mechanistically, lutein exerted antitumorigenic effects by inducing DNA damage and subsequently activating the ATR/Chk1/p53 signaling pathway in A549 cells. In vivo, lutein impeded tumor growth in mice and prolonged their survival. In conclusion, our findings demonstrate the antitumorigenic potential of lutein and reveal its molecular mechanism of action, suggesting that lutein is a promising candidate for clinical NSCLC treatment.

The anti-inflammatory effect of lutein in broilers is mediated by regulating Toll-like receptor 4/myeloid-differentiation-factor 88 signaling pathway.

The anti-inflammatory role of lutein has been widely recognized, however, the underlying mechanism is still not fully elucidated. Hence, the effects of lutein on the intestinal health and growth performance of broilers and the action of mechanism were investigated. 288 male yellow-feathered broilers (1-day old) were randomly allocated to 3 treatment groups with 8 replicates of 12 birds each, and the control group was fed a broken rice-soybean basal diet, while the test groups were fed a basal diet added with 20 mg/kg and 40 mg/kg of lutein (LU20, LU40), respectively. The feeding trial lasted for 21 d. The results showed that 40 mg/kg lutein supplementation tended to increase ADFI (P = 0.10) and ADG (P = 0.08) of broilers. Moreover, the addition of lutein caused a decreasing trend of gene expression and concentration of proinflammatory cytokines IL-1ß (P = 0.08, P = 0.10, respectively) and IL-6 (P = 0.06, P = 0.06, respectively) and also tended to decrease the gene expression of TLR4 (P = 0.09) and MyD88 (P = 0.07) while increasing gene expression and concentration of anti-inflammatory cytokines IL-4 and IL-10 (P < 0.05) in the jejunum mucosa of broilers. Additionally, lutein supplementation increased the jejunal villi height of broilers (P < 0.05) and reduced villi damage. The experiment in vitro showed that lutein treatment reduced the gene expression of IL-1ß, IL-6, and IFN-γ in chicken intestinal epithelial cells (P < 0.05). However, this effect was diminished after knock-down of TLR4 or MyD88 genes using RNAi technology. In conclusion, lutein can inhibit the expression and secretion of proinflammatory cytokines in the jejunum mucosa and promote intestinal development of broilers, and the anti-inflammatory effect may be achieved by regulating TLR4/MyD88 signaling pathway.

Lutein attenuates Propionibacterium acnes-induced inflammation by inhibiting pyroptosis of human keratinocyte cells via TLR4/NLRP3/Caspase-1 pathway.

BACKGROUND: Previous studies found Propionibacterium acnes (P. acnes) has a strong association with acne inflammation and cell pyroptosis. Because of the various side effects of current acne medicines, it is important to explore alternative drugs with anti-inflammatory activity against P. acnes. we explored the effect of Lutein on P. acnes-induced cell pyroptosis and accelerated the recovery of acne inflammation in vitro and vivo. METHODS: Lutein was utilized to expose HaCaT keratinocytes, then we reassessed the effect of Lutein on the cell apoptosis, pyroptotic-associated inflammatory factors and catabolic enzymes in heat-killed P. acnes-treated HaCaT cells. Next, living P. acnes was intradermally injected into the right ears of ICR mice to induce mice with acne inflammation, and the effect of Lutein on living P. acnes-induced inflammation was investigated. Moreover, we explored the mechanism of Lutein on TLR4/NLRP3/Caspase-1 pathways by ELISA, immunofluorescence microscopy, and western blot assay. RESULTS: Heat-killed P. acnes triggered remarkable cell pyroptosis, pyroptotic inflammatory factors and catabolic enzymes in HaCaT cells, including up-regulating interleukin (IL)-1ß, IL-18, TNF-α, MMP3, MMP13, ADAMTS4, and ADAMTS5, TLR4, NLRP3, caspase-1, and the ratio of gasdermin D to cleaved gasdermin D, whereas these effects were suppressed by Lutein. In addition, Lutein effectively improved ear redness, swelling, and the expression of TLR4, IL-1ß and TNF-α in vivo. Finally, NLRP3 activator (nigericin) increased caspase-1, IL-1ß and IL-18 level, while TLR4 inhibitor (TAK-242) significantly blocked this effect in heat-killed P. acnes-treated cells. CONCLUSIONS: Lutein attenuated P. acnes-caused pyroptosis of HaCaTs and the subsequent acne inflammation via the TLR4/NLRP3/Caspase-1 pathway.