Lutein is a tetraterpene carotenoid, which has been reported as an important antioxidant and it is widely used as a supplement. Oxidative stress participates in many human diseases, including different types of neurodegenerative disorders. Microglia, the primary immune effector cells in the central nervous system, are implicated in these disorders by producing harmful substances such as reactive oxygen species (ROS). The protective mechanisms which scavenge ROS include enzymes and antioxidant substances. The protective effects of different carotenoids against oxidative stress have been described previously. Our study focuses on the effects of lutein on antioxidant enzymes, cytokines and iron metabolism under stress conditions in BV-2 microglia. We performed cell culture experiments: BV-2 cells were treated with lutein and/or with H₂O₂; the latter was used for inducing oxidative stress in microglial cells. Real-time PCR was performed for gene expression analyses of antioxidant enzymes, and ELISA was used for the detection of pro- and anti-inflammatory cytokines. Our results show that the application of lutein suppressed the H₂O₂-induced ROS (10′: 7.5 ng + 10 µM H₂O₂, p = 0.0002; 10 ng/µL + 10 µM H₂O₂, p = 0.0007), influenced iron utilization and changed the anti-inflammatory and pro-inflammatory cytokine secretions in BV-2 cells. Lutein increased the IL-10 secretions compared to control (24 h: 7.5 ng/µL p = 0.0274; 10 ng/µL p = 0.0008) and to 10 µM H₂O₂-treated cells (24 h: 7.5 ng/µL + H₂O₂, p = 0.0003; 10 ng/µL + H₂O₂, p = 0.0003), while it decreased the TNFα secretions compared to H₂O₂ treated cells (24 h: 7.5 ng/µL + H₂O₂, p < 0.0001; 10 ng/µL + H₂O₂, p < 0.0001). These results contribute to understanding the effects of lutein, which may help in preventing or suppressing ROS-mediated microglia activation, which is related to neuronal degeneration in oxidative stress scenario.

The xanthophyll carotenoid lutein has been widely used as supplementation due to its protective effects in light-induced oxidative stress. Its antioxidant and anti-inflammatory features suggest that it has a neuroprotective role as well. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), which plays a key role in regulating brain function. Excess accumulation of intracellular glutamate accelerates an increase in the concentration of reactive oxygen species (ROS) in neurons leading to glutamate neurotoxicity. In this study, we focused on the effects of glutamate on SH-SY5Y neuroblastoma cells to identify the possible alterations in oxidative stress, inflammation, and iron metabolism that affect the neurological function itself and in the presence of antioxidant lutein. First, ROS measurements were performed, and then catalase (CAT) and Superoxide Dismutase (SOD) enzyme activity were determined by enzyme activity assay kits. The ELISA technique was used to detect proinflammatory TNFα, IL-6, and IL-8 cytokine secretions. Alterations in iron uptake, storage, and release were followed by gene expression measurements and Western blotting. Total iron level detections were performed by a ferrozine-based iron detection method, and a heme assay kit was used for heme measurements. The gene expression toward lipid-peroxidation was determined by RT-PCR. Our results show glutamate changes ROS, inflammation, and antioxidant enzyme activity, modulate iron accumulation, and may initiate lipid peroxidation in SH-SY5Y cells. Meanwhile, lutein attenuates the glutamate-induced effects on ROS, inflammation, iron metabolism, and lipid peroxidation. According to our findings, lutein could be a beneficial, supportive treatment in neurodegenerative disorders.

Carotenoids are substantially hydrophobic antioxidants. Hydrophobicity is this context is rather a disadvantage, because their utilization in medicine as antioxidants or in food chemistry as colorants would require some water dispersibility for their effective uptake or use in many other ways. In the past 15 years several attempts were made to synthetize partially hydrophilic carotenoids. This review compiles the recently synthetized hydrophilic carotenoid derivatives.

The protracted global COVID-19 pandemic urges the development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone. Their antiviral effect was tested against SARS-CoV-2 in Vero E6 cells, using a cell viability assay and quantitative PCR of the viral RNA, confirming their micromolar inhibitory activity against viral replication. Interestingly, two of the parent apocarotenoids, bixin and β-apo-8′carotenoic acid, exerted remarkable anti-SARS-CoV-2 activity. Mechanistic studies involved cathepsin L and B, as well as the main protease 3CLPro, and the results were rationalized by computational studies. Glycopeptide conjugates show dual inhibitory action, while apocarotenoids have mostly cathepsin B and L affinity. Since teicoplanin is a marketed antibiotic and the natural bixin is an approved, cheap and widely used red colorant food additive, these readily available compounds and their conjugates as potential antivirals are worthy of further exploration.

Flavonoids and carotenoids possess beneficial physiological effects, such as high antioxidant capacity, anticarcinogenic, immunomodulatory, and anti-inflammatory properties, as well as protective effects against UV light. The covalent coupling of hydrophobic carotenoids with hydrophilic flavonoids, such as daidzein and chrysin, was achieved, resulting in new amphipathic structures. 7-Azidohexyl ethers of daidzein and chrysin were prepared in five steps, and their azide-alkyne [4 + 2] cycloaddition with pentynoates of 8′-apo-β-carotenol, zeaxanthin, and capsanthin afforded carotenoid–flavonoid conjugates. The trolox-equivalent antioxidant capacity against ABTS^•+ radical cation and self-assembly of the final products were examined. The 1:1 flavonoid–carotenoid hybrids generally showed higher antioxidant activity than their parent flavonoids but lower than that of the corresponding carotenoids. The diflavonoid hybrids of zeaxanthin and capsanthin, however, were found to exhibit a synergistic enhancement in antioxidant capacities. ECD (electronic circular dichroism) and UV-vis analysis of zeaxanthin–flavonoid conjugates revealed that they form different optically active J-aggregates in acetone/water and tetrahydrofuran/water mixtures depending on the solvent ratio and type of the applied aprotic polar solvent, while the capsanthin derivatives showed no self-assembly. The zeaxanthin bis-triazole conjugates with daidzein and with chrysin, differing only in the position of a phenolic hydroxyl group, showed significantly different aggregation profile upon the addition of water.

Lutein and its cis-isomers occur in a lot of plants, including a variety of flowers. In this study, lutein isomers were produced via iodine-catalyzed isomerization, and four cis-isomers (9Z-, 9′Z-, 13Z-, and 13Z′) were isolated by means of column chromatography and semipreparative HPLC. The structures of the 9′Z- and 13′Z-isomers were elucidated via NMR measurements. These compounds were used as standards for the HPLC-DAD-MS determination of the carotenoid composition of the flowers of 20 plant species, in which lutein and its geometrical isomers are the main components. The flowers showed great variation in their cis- and trans-lutein content, and also in the presence or absence of other carotenoids, such as violaxanthin, neoxanthin, β-cryptoxanthin, and β-carotene. Some of the investigated flowers were found to be rich sources of lutein without zeaxanthin.