Green diatom mutants reveal an intricate biosynthetic pathway of fucoxanthin.

Fucoxanthin is a major light-harvesting pigment in ecologically important algae such as diatoms, haptophytes, and brown algae (Phaeophyceae). Therefore, it is a major driver of global primary productivity. Species of these algal groups are brown colored because the high amounts of fucoxanthin bound to the proteins of their photosynthetic machineries enable efficient absorption of green light. While the structure of these fucoxanthin-chlorophyll proteins has recently been resolved, the biosynthetic pathway of fucoxanthin is still unknown. Here, we identified two enzymes central to this pathway by generating corresponding knockout mutants of the diatom Phaeodactylum tricornutum that are green due to the lack of fucoxanthin. Complementation of the mutants with the native genes or orthologs from haptophytes restored fucoxanthin biosynthesis. We propose a complete biosynthetic path to fucoxanthin in diatoms and haptophytes based on the carotenoid intermediates identified in the mutants and in vitro biochemical assays. It is substantially more complex than anticipated and reveals diadinoxanthin metabolism as the central regulatory hub connecting the photoprotective xanthophyll cycle and the formation of fucoxanthin. Moreover, our data show that the pathway evolved by repeated duplication and neofunctionalization of genes for the xanthophyll cycle enzymes violaxanthin de-epoxidase and zeaxanthin epoxidase. Brown algae lack diadinoxanthin and the genes described here and instead use an alternative pathway predicted to involve fewer enzymes. Our work represents a major step forward in elucidating the biosynthesis of fucoxanthin and understanding the evolution, biogenesis, and regulation of the photosynthetic machinery in algae.

Antioxidant and Neuroprotective Effects of Fucoxanthin and Its Metabolite Fucoxanthinol: A Comparative In Vitro Study.

Fucoxanthin is the most abundant carotenoid found in marine brown algae that exhibits several healthy properties. Dietary fucoxanthin is metabolized in the intestine, plasma, and other tissues to various metabolites, including fucoxanthinol. In this regard, the contribution of fucoxanthinol to the healthy properties of its precursor, fucoxanthin, against pathogenetic events associated with neurodegenerative diseases remains unexplored. Here, we evaluated and compared the antioxidant and neuroprotective effects of the carotenoids fucoxanthin and fucoxanthinol in in vitro models of Alzheimer's (AD) and Parkinson's (PD) disease. Neuronal SH-SY5Y cells were used to evaluate the antioxidant properties of the carotenoids against ABTS radical in the membrane and cytoplasm and oxidative stress elicited by tert-butyl hydroperoxide using the 2',7'-dichlorodihydrofluorescein diacetate probe. We also assessed the ability of the carotenoids to increase the glutathione (GSH) and activate the Nrf2/Keap1/ARE pathway using the monochlorobimane probe and western blotting method, respectively. The neuroprotective effects of the carotenoids against the neurotoxicity generated by oligomers of Beta-Amyloid (1-42) peptide (OAß) and 6-hydroxydopamine (6-OHDA), which are neurotoxins of AD and PD, respectively, were finally evaluated in the same neuronal cells using the thiazolyl blue tetrazolium bromide assay. Both carotenoids could reach the cytoplasm, which explains the mainly free radical scavenging activity at this level. Notably, fucoxanthinol had higher and lower antioxidant activity than fucoxanthin at extracellular and cellular levels. Although studied carotenoids exerted the ability to activate the Nrf2/Keap1/ARE pathway, leading to an increase of intracellular GSH, our results suggested that the antioxidant activity of the carotenoids could be mainly attributed to their radical scavenging activity in neuronal membrane and cytoplasm, where they accumulate. Fucoxanthinol also shared similar neuroprotective effects as fucoxanthin against the neurotoxicity generated by OAß and 6-OHDA, suggesting a potential neuroprotective contribution to the action of fucoxanthin administered as a food supplement in in vivo experimental models. These results encourage further research to evaluate the bioavailability of fucoxanthinol and other metabolites of fucoxanthin at the brain level to elucidate the dietary neuroprotective potential of fucoxanthin.

The role of cis-zeatin in enhancing high-temperature resistance and fucoxanthin biosynthesis in Phaeodactylum tricornutum.

Phaeodactylum tricornutum a prominent source of industrial fucoxanthin production, faces challenges in its application due to its tolerance to high-temperature environments. This study investigates the physiological responses of P. tricornutum to high-temperature stress and its impact on fucoxanthin content, with a specific focus on the role of cis-zeatin. The results reveal that high-temperature stress inhibits P. tricornutum's growth and photosynthetic activity, leading to a decrease in fucoxanthin content. Transcriptome analysis shows that high temperature suppresses the expression of genes related to photosynthesis (e.g., psbO, psbQ, and OEC) and fucoxanthin biosynthesis (e.g., PYS, PDS1, and PSD2), underscoring the negative effects of high temperature on P. tricornutum. Interestingly, genes associated with cis-zeatin biosynthesis and cytokinesis signaling pathways exhibited increased expression under high-temperature conditions, indicating a potential role of cis-zeatin signaling in response to elevated temperatures. Content measurements confirm that high temperature enhances cis-zeatin content. Furthermore, the exogenous addition of cytokinesis mimetics or inhibitors significantly affected P. tricornutum's high-temperature resistance. Overexpression of the cis-zeatin biosynthetic enzyme gene tRNA DMATase enhanced P. tricornutum's resistance to high-temperature stress, while genetic knockout of tRNA DMATase reduced its resistance to high temperatures. Therefore, this research not only uncovers a novel mechanism for high-temperature resistance in P. tricornutum but also offers a possible alga species that can withstand high temperatures for the industrial production of fucoxanthin, offering valuable insights for practical utilization.IMPORTANCEThis study delves into Phaeodactylum tricornutum's response to high-temperature stress, specifically focusing on cis-zeatin. We uncover inhibited growth, reduced fucoxanthin, and significant cis-zeatin-related gene expression under high temperatures, highlighting potential signaling mechanisms. Crucially, genetic engineering and exogenous addition experiments confirm that the change in cis-zeatin levels could influence P. tricornutum's resistance to high-temperature stress. This breakthrough deepens our understanding of microalgae adaptation to high temperatures and offers an innovative angle for industrial fucoxanthin production. This research is a pivotal step toward developing heat-resistant microalgae for industrial use.

Mediator subunit MED8 interacts with heat shock transcription factor HSF3 to promote fucoxanthin synthesis in the diatom Phaeodactylum tricornutum.

Fucoxanthin, a natural carotenoid that has substantial pharmaceutical value due to its anticancer, antioxidant, antiobesity, and antidiabetic properties, is biosynthesized from glyceraldehyde-3-phosphate (G3P) via a series of enzymatic reactions. However, our understanding of the transcriptional mechanisms involved in fucoxanthin biosynthesis remains limited. Using reverse genetics, the med8 mutant was identified based on its phenotype of reduced fucoxanthin content, and the biological functions of MED8 in fucoxanthin synthesis were characterized using approaches such as gene expression, protein subcellular localization, protein-protein interaction and chromatin immunoprecipitation assay. Gene-editing mutants of MED8 exhibited decreased fucoxanthin content as well as reduced expression levels of six key genes involved in fucoxanthin synthesis, namely DXS, PSY1, ZDS-like, CRTISO5, ZEP1, and ZEP3, when compared to the wild-type (WT) strain. Furthermore, we showed that MED8 interacts with HSF3, and genetic analysis revealed their shared involvement in the genetic pathway governing fucoxanthin synthesis. Additionally, HSF3 was required for MED8 association with the promoters of the six fucoxanthin synthesis genes. In conclusion, MED8 and HSF3 are involved in fucoxanthin synthesis by modulating the expression of the fucoxanthin synthesis genes. Our results increase the understanding of the molecular regulation mechanisms underlying fucoxanthin synthesis in the diatom P. tricornutum.

Fucoxanthin extract ameliorates obesity associated with modulation of bile acid metabolism and gut microbiota in high-fat-diet fed mice.

PURPOSE: Fucoxanthin extract (FX) is a type of carotenoid with a beneficial effect against obesity. The purpose of this study was to explore its precise action mechanism of losing weight. METHODS: A high-fat diet induced obesity mouse model was established to study the effects of different doses of FX on C57BL/6J male mice for 12 weeks. Following intervention, serum indices, tissue sections, liver gene expression, and intestinal microorganisms were analyzed. RESULTS: FX at low, medium, and high dosages (80, 160, and 320 mg/kg/day, respectively) for 12 weeks was associated with the lower body weight of mice when compared to that of high-fat-diet fed mice. It also improved glucose tolerance as well as serum lipid levels, and reduced fat accumulation. Significant regulation of bile acid metabolism and intestinal microbiota may contribute to the above effects. The bile acids in the FXH group were significantly increased. A low-dose and a medium-dose FX increased the level of transmembrane G protein-coupled receptor 5 (TGR5); a low-dose and high-dose FX increased the farnesoid X receptor (FXR) expression, and a medium-dose had no effect. 16S rRNA sequencing indicated that the Lachnospiraceae and Oscillospiraceae contributed to the beneficial effects of FX. CONCLUSION: Our study sheds light on mechanisms behind the weight-lowering of FX, and manifested that bile acid metabolism and gut microbiota may be potential therapies. These results support that FX is a valuable candidate for promoting health and alleviating obesity.

Mixotrophic culture enhances fucoxanthin production in the haptophyte Pavlova gyrans.

Fucoxanthin is a versatile substance in the food and pharmaceutical industries owing to its excellent antioxidant and anti-obesity properties. Several microalgae, including the haptophyte Pavlova spp., can produce fucoxanthin and are potential industrial fucoxanthin producers, as they lack rigid cell walls, which facilitates fucoxanthin extraction. However, the commercial application of Pavlova spp. is limited owing to insufficient biomass production. In this study, we aimed to develop a mixotrophic cultivation method to increase biomass and fucoxanthin production in Pavlova gyrans OPMS 30543X. The effects of culturing OPMS 30543X with different organic carbon sources, glycerol concentrations, mixed-nutrient conditions, and light intensities on the consumption of organic carbon sources, biomass production, and fucoxanthin accumulation were analyzed. Several organic carbon sources, such as glycerol, glucose, sucrose, and acetate, were examined, revealing that glycerol was well-consumed by the microalgae. Biomass and fucoxanthin production by OPMS 30543X increased in the presence of 10 mM glycerol compared to that observed without glycerol. Metabolomic analysis revealed higher levels of the metabolites related to the glycolytic, Calvin-Benson-Bassham, and tricarboxylic acid cycles under mixotrophic conditions than under autotrophic conditions. Cultures grown under mixotrophic conditions with a light intensity of 100 µmol photons m-2 s-1 produced more fucoxanthin than autotrophic cultures. Notably, the amount of fucoxanthin produced (18.9 mg/L) was the highest reported thus far for Pavlova species. In conclusion, the use of mixotrophic culture is a promising strategy for increasing fucoxanthin production in Pavlova species. KEY POINTS: • Glycerol enhances biomass and fucoxanthin production in Pavlova gyrans • Metabolite levels increase under mixotrophic conditions • Mixotrophic conditions and medium-light intensity are appropriate for P. gyrans.

Effect of Iron Concentration on the Co-Production of Fucoxanthin and Fatty Acids in Conticribra weissflogii.

The production of fucoxanthin and fatty acids in Conticribra weissflogii has been examined, but there is still a lack of understanding regarding the impact of trace elements, including iron, on their co-production. To address this knowledge gap, this study investigated the effects of FeCl3·6H2O on the growth, fucoxanthin, and fatty acids of C. weissflogii. The findings revealed that the highest cell density (1.9 × 106 cells mL-1), cell dry weight (0.89 ± 0.15 g L-1), and total fatty acid concentration (83,318.13 µg g-1) were achieved at an iron concentration of 15.75 mg L-1, while the maximum carotenoid and fucoxanthin contents were obtained at an iron concentration of 3.15 mg L-1. The study demonstrated that the content of the active substance in C. weissflogii could be increased by adjusting the iron concentration, providing new information as to the more efficient co-production of fucoxanthin and fatty acids and offering experimental support for large-scale production.

Antiviral Potential of Fucoxanthin, an Edible Carotenoid Purified from Sargassum siliquastrum, against Zika Virus.

Considering the lack of antiviral drugs worldwide, we investigated the antiviral potential of fucoxanthin, an edible carotenoid purified from Sargassum siliquastrum, against zika virus (ZIKV) infection. The antiviral activity of fucoxanthin was assessed in ZIKV-infected Vero E6 cells, and the relevant structural characteristics were confirmed using molecular docking and molecular dynamics (MD) simulation. Fucoxanthin decreased the infectious viral particles and nonstructural protein (NS)1 mRNA expression levels at concentrations of 12.5, 25, and 50 µM in ZIKV-infected cells. Fucoxanthin also decreased the increased mRNA levels of interferon-induced proteins with tetratricopeptide repeat 1 and 2 in ZIKV-infected cells. Molecular docking simulations revealed that fucoxanthin binds to three main ZIKV proteins, including the envelope protein, NS3, and RNA-dependent RNA polymerase (RdRp), with binding energies of -151.449, -303.478, and -290.919 kcal/mol, respectively. The complex of fucoxanthin with RdRp was more stable than RdRp protein alone based on MD simulation. Further, fucoxanthin bonded to the three proteins via repeated formation and disappearance of hydrogen bonds. Overall, fucoxanthin exerts antiviral potential against ZIKV by affecting its three main proteins in a concentration-dependent manner. Thus, fucoxanthin isolated from S. siliquastrum is a potential candidate for treating zika virus infections.

Understanding the Impact of Nitrogen Availability: A Limiting Factor for Enhancing Fucoxanthin Productivity in Microalgae Cultivation.

This study aimed to investigate the regulation of fucoxanthin (FX) biosynthesis under various nitrogen conditions to optimize FX productivity in Phaeodactylum tricornutum. Apart from light, nitrogen availability significantly affects the FX production of microalgae; however, the underlying mechanism remains unclear. In batch culture, P. tricornutum was cultivated with normal (NN, 0.882 mM sodium nitrate), limited (LN, 0.22 mM), and high (HN, 8.82 mM) initial nitrogen concentrations in f/2 medium. Microalgal growth and photosynthetic pigment production were examined, and day 5 samples were subjected to fucoxanthin-chlorophyll a/c-binding protein (FCP) proteomic and transcriptomic analyses. The result demonstrated that HN promoted FX productivity by extending the exponential growth phase for higher biomass and FX accumulation stage (P1), showing a continuous increase in FX accumulation on day 6. Augmented FX biosynthesis via the upregulation of carotenogenesis could be primarily attributed to enhanced FCP formation in the thylakoid membrane. Key proteins, such as LHC3/4, LHCF8, LHCF5, and LHCF10, and key genes, such as PtPSY, PtPDS, and PtVDE, were upregulated under nitrogen repletion. Finally, the combination of low light and HN prolonged the P1 stage to day 10, resulting in maximal FX productivity to 9.82 ± 0.56 mg/L/day, demonstrating an effective strategy for enhancing FX production in microalgae cultivation.

Nutritional Value and Productivity Potential of the Marine Microalgae Nitzschia laevis, Phaeodactylum tricornutum and Isochrysis galbana.

Microalgae are considered promising sustainable feedstocks for the production of food, food additives, feeds, chemicals and various high-value products. Marine microalgae Phaeodactylum tricornutum, Isochrysis galbana and Nitzschia laevis are rich in fucoxanthin, which is effective for weight loss and metabolic diseases. The selection of microalgae species with outstanding nutritional profiles is fundamental for novel foods development, and the nutritional value of P. tricornutum, I. galbana and N. laevis are not yet fully understood. Hence, this study investigates and analyzes the nutritional components of the microalgae by chromatography and mass spectrometry, to explore their nutritional and industrial application potential. The results indicate that the three microalgae possess high nutritional value. Among them, P. tricornutum shows significantly higher levels of proteins (43.29%) and amino acids, while I. galbana has the highest content of carbohydrates (25.40%) and lipids (10.95%). Notwithstanding that P. tricornutum and I. galbana have higher fucoxanthin contents, N. laevis achieves the highest fucoxanthin productivity (6.21 mg/L/day) and polyunsaturated fatty acids (PUFAs) productivity (26.13 mg/L/day) because of the competitive cell density (2.89 g/L) and the advantageous specific growth rate (0.42/day). Thus, compared with P. tricornutum and I. galbana, N. laevis is a more promising candidate for co-production of fucoxanthin and PUFAs.

Production of Fucoxanthin from Microalgae Isochrysis galbana of Djibouti: Optimization, Correlation with Antioxidant Potential, and Bioinformatics Approaches.

Fucoxanthin, a carotenoid with remarkable antioxidant properties, has considerable potential for high-value biotechnological applications in the pharmaceutical, nutraceutical, and cosmeceutical fields. However, conventional extraction methods of this molecule from microalgae are limited in terms of cost-effectiveness. This study focused on optimizing biomass and fucoxanthin production from Isochrysis galbana, isolated from the coast of Tadjoura (Djibouti), by testing various culture media. The antioxidant potential of the cultures was evaluated based on the concentrations of fucoxanthin, carotenoids, and total phenols. Different nutrient formulations were tested to determine the optimal combination for a maximum biomass yield. Using the statistical methodology of principal component analysis, Walne and Guillard F/2 media were identified as the most promising, reaching a maximum fucoxanthin yield of 7.8 mg/g. Multiple regression models showed a strong correlation between antioxidant activity and the concentration of fucoxanthin produced. A thorough study of the optimization of I. galbana growth conditions, using a design of experiments, revealed that air flow rate and CO2 flow rate were the most influential factors on fucoxanthin production, reaching a value of 13.4 mg/g. Finally, to validate the antioxidant potential of fucoxanthin, an in silico analysis based on molecular docking was performed, showing that fucoxanthin interacts with antioxidant proteins (3FS1, 3L2C, and 8BBK). This research not only confirmed the positive results of I. galbana cultivation in terms of antioxidant activity, but also provided essential information for the optimization of fucoxanthin production, opening up promising prospects for industrial applications and future research.

A Standardized Extract of Microalgae Phaeodactylum tricornutum (Mi136) Inhibit D-Gal Induced Cognitive Dysfunction in Mice.

The microalgae Phaeodactylum tricornutum (PT) is distinguished by its rich nutrient profile, characterized by well-documented neuroprotective activities, including fucoxanthin (FX), a major carotenoid and polyunsaturated omega-3 fatty acids (n-3 PUFA). The current study aims to evaluate the protective effects of a standardized extract of PT (Mi136) containing 2% FX on cognitive function, oxidative stress, and inflammation parameters in a mouse model of accelerated aging. Seventy-two (72) male mice were randomly assigned to the blank control group (BC), negative control group (NC), and four similar microalgae extract of PT groups (branded as BrainPhyt™) with different human equivalent doses to evaluate potential dose-response effects. From day 01 to day 51, mice in the BC group were injected with a 0.9% normal saline solution, while mice in all other groups were subcutaneously injected with D-galactose (D-Gal) at a dose of 150 mg/kg once per day, five days per week. Results indicated that, for the three higher microalgae extract of PT dose groups, spatial cognitive function, swim latency, and step-through latency impairments induced by chronic D-Gal intoxication were significantly and fully inhibited, with mean values similar to those in the BC group during each day of testing. Similar benefits were observed in biochemical analysis, specifically regarding brain and plasma levels of lipid peroxidation, TNF-α, and IL-6 markers. These data underscore the positive effects of a standardized extract of PT containing 2% FX on cognitive function parameters such as spatial working memory, long-term memory, and short-term memory through the regulation of oxidative stress and inflammation pathways.

Fucoxanthin induces human melanoma cytotoxicity by thwarting the JAK2/STAT3/BCL-xL signaling axis.

Melanoma is the most lethal skin malignancy. Fucoxanthin is a marine carotenoid with significant anticancer activities. Intriguingly, Fucoxanthin's impact on human melanoma remains elusive. Signal Transducer and Activator of Transcription 3 (STAT3) represents a promising target in cancer therapy due to its persistent activation in various cancers, including melanoma. Herein, we revealed that Fucoxanthin is cytotoxic to human melanoma cell lines A2758 and A375 while showing limited cytotoxicity to normal human melanocytes. Apoptosis is a primary reason for Fucoxanthin's melanoma cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk drastically abrogated Fucoxanthin-elicited clonogenicity blockage. Besides, Fucoxanthin downregulated tyrosine 705-phosphorylated STAT3 (p-STAT3 (Y705)), either inherently present in melanoma cells or inducible by interleukin 6 (IL-6) stimulation. Notably, ectopic expression of STAT3-C, a dominant-active STAT3 mutant, abolished Fucoxanthin-elicited melanoma cell apoptosis and clonogenicity inhibition, supporting the pivotal role of STAT3 blockage in Fucoxanthin's melanoma cytotoxicity. Moreover, Fucoxanthin lowered BCL-xL levels by blocking STAT3 activation, while ectopic BCL-xL expression rescued melanoma cells from Fucoxanthin-induced killing. Lastly, Fucoxanthin was found to diminish the levels of JAK2 with dual phosphorylation at tyrosine residues 1007 and 1008 in melanoma cells, suggesting that Fucoxanthin impairs STAT3 signaling by blocking JAK2 activation. Collectively, we present the first evidence that Fucoxanthin is cytotoxic selectively against human melanoma cells while sparing normal melanocytes. Mechanistically, Fucoxanthin targets the JAK2/STAT3/BCL-xL antiapoptotic axis to provoke melanoma cell death. This discovery implicates the potential application of Fucoxanthin as a chemopreventive or therapeutic strategy for melanoma management.

A Review of Fucoxanthin Biomanufacturing from Phaeodactylum tricornutum.

Microalgae, compared to macroalgae, exhibit advantages such as rapid growth rates, feasible large-scale cultivation, and high fucoxanthin content. Among these microalgae, Phaeodactylum tricornutum emerges as an optimal source for fucoxanthin production. This paper comprehensively reviews the research progress on fucoxanthin production using Phaeodactylum tricornutum from 2012 to 2022, offering detailed insights into various aspects, including strain selection, media optimization, nutritional requirements, lighting conditions, cell harvesting techniques, extraction solvents, extraction methodologies, as well as downstream separation and purification processes. Additionally, an economic analysis is performed to assess the costs of fucoxanthin production from Phaeodactylum tricornutum, with a comparative perspective to astaxanthin production from Haematococcus pluvialis. Lastly, this paper discusses the current challenges and future opportunities in this research field, serving as a valuable resource for researchers, producers, and industry managers seeking to further advance this domain.

Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway.

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.

Fucoxanthin Inhibits the Proliferation and Metastasis of Human Pharyngeal Squamous Cell Carcinoma by Regulating the PI3K/Akt/mTOR Signaling Pathway.

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

Assessing the impact of temperature, pH, light and chemical oxidation on fucoxanthin colour changes, antioxidant activity and the resulting metabolites.

BACKGROUND: The present study evaluated the effects of temperature, pH, light and chemical oxidation on fucoxanthin changes in terms of colour, antioxidant activity and metabolomic profile. Additionally, the correlation between antioxidant activity and identified metabolites was analysed. RESULTS: It was found that colour change was significantly reduced at elevated heat (100 °C, *∆E = 0.81 ± 0.05), reduced pH (pH 3, *∆E = 0.59 ± 0.04) and length of light exposure (*∆E = 3.16 ± 0.04). Antioxidant activity decreased under all treatments. Among the temperatures tested, fucoxanthin exhibited the highest activity at 60 °C, ranging from 0.92 to 3.04 mg Trolox equivalents (TE) g-1. Significant activity reductions (P < 0.05) were observed as a result of pH changes in the 2,2-diphenyl-1-picrylhydrazyl and ß-carotene bleaching assays. Exposure to light 2: warm white lamp for 120 h significantly reduced antioxidant activity (0.01 to 1.70 mg TE g-1). Chemical oxidation also led to reduced activity, ranging from 0.18 to 0.29 mg TE g-1. Multivariate data analysis revealed distinct profiles for temperature, pH, light and chemical oxidation treatments. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics analysis identified 10 metabolites, and significant correlations (P < 0.05) indicate that these metabolites contributed to the samples' antioxidant activities. CONCLUSION: In conclusion, fucoxanthin tolerates well at 60 °C, within pH range 3-9, and within 8 h of light exposure, as indicated by its consistent antioxidant activity and minimal colour change. Each treatment resulted in distinct metabolite concentrations, as shown by LC-MS/MS-based metabolomics analysis. Further research into these metabolites could advance the understanding of their roles and aid in optimising processing conditions to favour beneficial metabolites. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Scope and challenges of seaweed utilization in food and nutraceutical industry in India: a review.

Seaweeds are an excellent source of unique antioxidant phytochemicals, dietary fibres, essential amino acids, vitamins, polyunsaturated fatty acids and minerals. The presence of such structurally diverse and high value bioactive compounds has led to popularization of seaweed as functional food ingredient in global health supplement market. India, with a long coastline of 8100 km and exclusive economic zone of 2.17 million km2, is rich in diverse seaweed resources belonging to almost 700 species. However, food and nutraceutical application of Indian seaweed is highly constrained. Apart from Kappaphycus alvarezii, there is no systematic commercial cultivation of seaweed in India. The regulatory framework for use of seaweed as food is still developing and consumer acceptance is still low. However, there is a timely and renewed interest from different government agencies and research organisations to develop a thriving food and nutraceutical industry using India's vast seaweed resources. The review briefly describes the nutritional and functional food potential of the seaweed and goes on to discuss the scope of seaweed utilization in food and nutraceutical industry in India. Further, the review has identified the regulatory challenges and quality control requirements for use of seaweeds in food and nutraceuticals.

[Specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity].

The development of specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity is an important task of health concern in the Russian Federation. The aim of the study was to develop specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity, the distinctive features of which are the presence of functional ingredients and bioactive compounds that meet modern safety requirements, have a hypolipidemic effect and influence on body weight. Material and methods. As a source of fucoxanthin, an oil extract from the thallom (stratum) of the annual Undaria pinnatifida brown algae was used, obtained by re-extraction with soy oil for 8 hours from a glycerin extract (extractant - 60% glycerin solution, the duration of the process - 8 h). The determination of organoleptic parameters was carried out at a temperature of 20 °C 12 h after manufacture using standard methods. Organoleptic parameters were determined in the following sequence: consistency, appearance, color, smell, taste. Physical and chemical characteristics (mass content of fat, moisture, egg products in terms of dry yolk, acidity in terms of acetic acid, emulsion stability), acid and peroxide values were studied by standard methods. Fatty acid analysis of lipids was performed by gas-liquid chromatography. The fucoxanthin content was determined by spectrophotometric method. Results. The presented formulations of lipid compositions as the fat base of specialized oil-fat emulsion food systems for the prevention of hyperlipidemia and obesity included Schizochytrium sp. microalgae oil in a mass fraction of 3-6% as a source of ω-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic and docosahexaenoic acids). An oil extract of U. pinnatifida brown algae in a mass fraction of 48-54% was used as a source of fucoxanthin. The total content of PUFA was significantly high - at least 73%, ω-6 PUFA prevailed (48.0-49.1%). However, the high content of ω-3 PUFA (at least 25%) should be also noted. The ratio of ω-3 to ω-6 PUFA was 1:1.72-1:1.90, which is atypical for individual vegetable oils traditionally used as the fat phase in fat-and-oil emulsion systems. The fucoxanthin content in the presented lipid compositions was 6.4-7.2 mg/100 ml. Edible fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity (mayonnaise and mayonnaise sauces) with a given ratio of ω-3:ω-6 PUFA containing eicosopentaenoic and docosahexaenoic acids, as well as fucoxanthin, have been obtained. The extract of U. pinnatifida brown algae, containing fucoxanthin, significantly slowed down the processes of lipid oxidation and hydrolysis, as evidenced by changes in the peroxide and acid values of fat isolated from specialized fat-and-oil emulsion systems for the prevention of hyperlipidemia and obesity. Conclusion. Specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity (mayonnaise and mayonnaise sauces with different oil phase content), containing fucoxanthin, having an optimized fatty acid composition, a given ratio of ω-3:ω-6 PUFA, high content of essential PUFA (eicosopentaenoic and docosohexaenoic acids) are safe food products with traditional organoleptic characteristics and specified physical and chemical parameters.

The Heat Shock Transcription Factor PtHSF1 Mediates Triacylglycerol and Fucoxanthin Synthesis by Regulating the Expression of GPAT3 and DXS in Phaeodactylum tricornutum.

In addition to being important primary productive forces in marine ecosystems, diatoms are also rich in bioactive substances such as triacylglycerol and fucoxanthin. However, little is known about the transcriptional mechanisms underlying the biosynthesis of these substances. In this study, we found that the heat shock transcription factor PtHSF1 positively regulated the synthesis of triacylglycerol and fucoxanthin in Phaeodactylum tricornutum. Overexpression of PtHSF1 could increase the contents of triacylglycerol and fucoxanthin and upregulate key enzyme genes involved in the triacylglycerol and fucoxanthin biosynthesis pathways. On the other hand, gene silencing of PtHSF1 reduced the contents of triacylglycerol and fucoxanthin and the expression of the key enzyme genes involved in the triacylglycerol and fucoxanthin biosynthesis pathways. Further biochemical analysis revealed that PtHSF1 upregulated glycerol-2-phosphate acyltransferase 3 (GPAT3) and 1-deoxy-d-xylulose 5-phosphate synthase (DXS) by directly binding to their promoters, while genetic analysis demonstrated that PtHSF1 acted upstream of GPAT3 and DXS to regulate triacylglycerol and fucoxanthin synthesis. Therefore, in addition to elucidating the regulation mechanisms underlying PtHSF1-mediated triacylglycerol and fucoxanthin synthesis, this study also provided a candidate target for metabolic engineering of triacylglycerol and fucoxanthin in P. tricornutum.