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.

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.

Optimizing color enhancement in dried Penaeus vannamei through high-humidity hot air impingement cooking: Enzyme inactivation, reduced drying time, and Maillard reaction inhibition.

This study was aimed to evaluate the potential of high-humidity hot air impingement cooking (HHAIC) on Penaeus vannamei, focusing on its drying characteristics, microstructure, water distribution, enzyme activity, astaxanthin content, antioxidant capacity, color, and Maillard reaction. Results demonstrated that a 3 min HHAIC significantly improved the shrimp's color and optimized astaxanthin content with a notable increase in scavenging capacity based on an in-vitro as antioxidation activity evaluation. Compared to the untreated samples, HHAIC could significantly inactivate polyphenol oxidase by 95.76%. Also, it suppressed the Maillard reaction by decreasing 5-hydroxymethylfurfural content and shortened the drying time by 40%. In addition, the low-field nuclear magnetic resonance and microstructure analysis showed alterations in the shrimp muscle fiber structure and water distribution. This study indicated that HHAIC could elevate quality, enhance appearance, and reduce the processing time of dried shrimp, presenting valuable implications for industry progress.

Co-encapsulation of curcumin and fucoxanthin in solid-in-oil-in-water multilayer emulsions: Characterization, stability and programmed sequential release.

To enhance the bioavailability of bioactives with varying efficacy in the gastrointestinal tract (GIT), a co-delivery system of solid-in-oil-in-water (S/O/W) emulsion was designed for the co-encapsulation of two bioactives in this paper. S/O/W emulsions were fabricated utilizing fucoxanthin (FUC)-loaded nanoparticles (NPs) as the solid phase, coconut oil containing curcumin (Cur) as the oil phase, and carboxymethyl starch (CMS)/propylene glycol alginate (PGA) complex as the aqueous phase. The high entrapment efficiency of Cur (82.3-91.3%) and FUC (96.0-96.1%) was found in the CMS/PGA complex-stabilized S/O/W emulsions. Encapsulation of Cur and FUC within S/O/W emulsions enhanced their UV and thermal stabilities. In addition, S/O/W emulsions prepared with CMS/PGA complexes displayed good stability. More importantly, the formed S/O/W emulsion possessed programmed sequential release characteristics, delivering Cur and FUC to the small intestine and colon, respectively. These results contributed to designing co-delivery systems for the programmed sequential release of two hydrophobic nutrients in the GIT.

Revealing the potential effects of oil phase on the stability and bioavailability of astaxanthin contained in Pickering emulsions: In vivo, in vitro and molecular dynamics simulation analysis.

This study investigated the effects of oil phases on the encapsulation rate, storage stability, and bioavailability of astaxanthin (ASTA) in Pickering emulsions (PEs). Results showed PEs of mixed oils (olive oil/edible tea oil) had excellent encapsulation efficiency (about 96.0%) and storage stability of ASTA. In vitro simulated gastrointestinal digestion results showed the mixed oil PE with a smaller interfacial area and higher monounsaturated fatty acid content may play a better role in improving ASTA retention and bioaccessibility. In vivo absorption results confirmed the mixed oil PE with an olive oil/edible tea oil of 7:3 was more favorable for ASTA absorption. Molecular dynamics simulation showed ASTA bound more strongly and stably to fatty acid molecules in the system of olive oil/edible tea oil of 7:3; and van der Waals force was the main binding force. NMR further proved there really were interactions between ASTA and four main fatty acids.

[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.

Controlling release of astaxanthin in ß-sitosterol oleogel-based emulsions via different self-assembled mechanisms and composition of the oleogelators.

In this study, three types of ß-sitosterol-based oleogels (ß-sitosterol + Î³-oryzanol oleogels, ß-sitosterol + lecithin, oleogels and ß-sitosterol + monostearate oleogels), loaded with astaxanthin, were employed as the oil phase to create oleogel-based emulsions (SO, SL, and SM) using high-pressure homogenization. The microstructure revealed that fine-scale crystals were dispersed within the oil phase of the droplets in the ß-sitosterol oleogel-based emulsion. The bioaccessibility of astaxanthin was found to be 58.13 %, 51.24 %, 36.57 %, and 45.72 % for SM, SL, SO, and the control group, respectively. Interestingly, the release of fatty acids was positively correlated with the availability of astaxanthin (P = 0.981). Further analysis of FFAs release and kinetics indicated that the structural strength of the oil-phase in the emulsions influenced the degree and rate of lipolysis. Additionally, the micellar fraction analysis suggested that the nature and composition of the oleogelators in SM and SL also impacted lipolysis and the bioaccessibility of astaxanthin. Furthermore, interfacial binding of lipase and isothermal titration calorimetry (ITC) measurements revealed that the oleogel network within the oil phase of the emulsion acted as a physical barrier, hindering the interaction between lipase and lipid. Overall, ß-sitosterol oleogel-based emulsions offer a versatile platform for delivering hydrophobic molecules, enhancing the bioavailability of active compounds, and achieving sustained release.

Subcritical water-assisted fish gelatin hydrolysis for astaxanthin-loaded fish oil emulsion stability.

Though gelatin emulsifying properties have been intensively studied, how low-molecular-weight (LMW) fish gelatin affects astaxanthin (AST)-loaded fish oil emulsion stability remains elusive. In this study, subcritical water hydrolysis (SWH)-modified LMW fish gelatin (SWHG) was produced from 110 °C to 180 °C and used to enhance the AST steadiness in oil/water emulsions in the presence of an emulsifier, lecithin. In the prepared emulsions, the surface charge increased while droplet size decreased with the decrease in gelatin MW due to the reduced thickness of the adsorbed gelatin membrane. LMW gelatin and lecithin could form a firm-absorbed layer on the droplet surface by electrostatic interaction between amide groups of gelatin molecules and phosphate groups of lecithin, thus stabilizing the emulsions. SWHG improved the creaming stability of the emulsions and hindered the oxygen- and light-induced AST degradation for 11 months compared to high MW gelatin. Whereas, the control emulsion showed noticeable phase separation after two weeks of storage. These findings prove the advantage of the SWH approach and propose the use of SWHG in oil-in-water emulsions for AST stabilization.

PEGylated-liposomal astaxanthin ameliorates Aß neurotoxicity and Alzheimer-related phenotypes by scavenging formaldehyde.

Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aß) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aß aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aß deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aß neurotoxicity by both degrading FA and reducing FA-induced Aß assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aß oligomerization and extracellular Aß-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD.

Hydrolytic efficiency and isomerization during de-esterification of natural astaxanthin esters by saponification and enzymolysis

Background: Astaxanthin from natural sources is typically esterified with fatty acids; hence, it must be hydrolyzed to remove esters before identification and quantification by conventional HPLC. Alkaline-catalyzed saponification and enzyme-catalyzed enzymolysis are the most commonly used de-esterification methods. However, information on the efficiency and isomerization during de-esterification of natural astaxanthin esters by these two methods remains scarce. Therefore, we conducted two HPLC-based experiments to determine which method is better for hydrolyzing astaxanthin esters. Results: To assess the effect of enzymolysis (0.67 U/mL cholesterol esterase, at 37°C) and saponification (0.021 M NaOH, at 5°C) conditions on free astaxanthin recovery and destruction or structural transformation of astaxanthin, we varied the total treatment time across a range of 195 min. The results showed that enzymolysis and saponification were complete in 60 min and 90 min, respectively. After complete hydrolysis, the maximum free astaxanthin recovery obtained by enzymolysis was 42.6% more than that obtained by saponification. The identification of by-products, semi-astacene and astacene, during the process of saponification also indicated that a more severe degradation of astaxanthin occurred during saponification. Moreover, the composition of astaxanthin isomers during saponification was similar to that of the isomers during enzymolysis between 30 min and 75 min (all-trans:9-cis:13-cis = 21:3:1, approximately) but dramatically changed after 90 min, whereas the composition in the enzymolysis treatment remained relatively stable throughout. Conclusion: Compared with saponification, enzymolysis with cholesterol esterase was recommended as a more accurate method for de-esterification of natural astaxanthin esters for further qualitative and quantitative HPLC analysis.