Ultrasound-mediated fucoxanthin rich oil nanoemulsions stabilized by κ-carrageenan: Process optimization, bio-accessibility and cytotoxicity.

This work aims to produce and optimize a κ-carrageenan-based nanoemulsion (NE) to encapsulate seaweed oil, which is rich in fucoxanthin (FX), using ultrasound-assisted emulsification. κ-Carrageenan was produced using subcritical water, and seaweed oil was extracted using supercritical carbon dioxide with sunflower oil as the co-solvent. Response surface methodology (RSM) was used to understand the influence of several process parameters such as ultrasound amplitude, time, temperature, and duty cycle to produce an NE. The RSM factor was used to focus on droplet size, polydispersity index, zeta potential, viscosity, antioxidant, FX, encapsulation efficiency, and emulsion stability. Our outcomes suggested that the ultrasound process had a noteworthy influence on the NE. The best conditions to obtain an NE were an ultrasound amplitude of 87 µm, a sonication time of 394 s, a temperature of 60 °C, and a duty cycle of 50%. The resulting NE was studied by UV-Vis, Fourier-transform infrared spectroscopy, thermal gravimetric analysis, differential scanning calorimetry, scanning electron microscopy, atomic force microscopy, and X-ray diffraction. Moreover, the NE obtained from optimized conditions was checked for fatty acid content, color, oxidative stability, in vitro digestion, bioaccessibility of FX, and cytotoxicity. The results obtained suggest that lower droplet size of the emulsion can improve oxidative stability, in vitro digestion, bioaccessibility of FX, and good cell inhibition against a few cell lines. Therefore, a κ-carrageenan-stabilized NE can be used as a potential delivery system to endorse applications of seaweed oil, which is rich in FX, in functional foods, beverage systems, and pharmaceuticals.

Water-dispersible astaxanthin-rich nanopowder: preparation, oral safety and antioxidant activity in vivo.

In this research, astaxanthin-rich nanopowder was prepared by nanoencapsulation and freeze-drying techniques with enhanced bioavailability and antioxidant activities. The nanopowder showed a maximum solubility of 230 mg mL-1 with an astaxanthin content as high as 2.9%. Compared with free astaxanthin, the astaxanthin-loaded nanopowder exhibited a more efficient antioxidant effect: an oral dose of 0.9 mg per kg BW significantly reduced the malondialdehyde and protein carbonyl contents, and increased the glutathione content as well as the superoxide dismutase activities in alcohol-induced acute hepatic injured mice, and maintained these oxidative stress indicators at a normal level for a longer period when treated with nanoencapsulated-astaxanthin than free astaxanthin. Simulated gastrointestinal tract studies demonstrated that the nanopowder with pH and DNase I-dependent dissociation properties delivered astaxanthin efficiently to the small intestine. Astaxanthin-rich nanopowder with a dose as high as 2.4 mg per kg BW (equivalent to astaxanthin) showed no chronic toxicity to mice in terms of hematology and pathological histology, indicating its impressive biocompatibility for biomedical applications. Pharmacokinetics and relative bioavailability (207%) of the nanopowder further proved that DNA/chitosan nanocarriers significantly improved the delivery efficiency of astaxanthin. With enhanced bioavailability and antioxidant activities, this novel type of astaxanthin-loaded nanopowder is expected to find broad application in the food and drug industry.

The effect of astaxanthin and cadmium on rat erythrocyte G6PD, 6PGD, GR, and TrxR enzymes activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro.

In this study, the effects of astaxanthin (AST) that belongs to carotenoid family and cadmium (Cd), which is an important heavy metal, on rat erythrocyte G6PD, 6PGD, GR, and TrxR enzyme activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro were studied. In in vitro studies, 6PGD enzyme was purified from rat erythrocytes with 2',5'-ADP Sepharose4B affinity chromatography. Results showed inhibition of enzyme by Cd at IC50 ; 346.5 µM value and increase of 6PGD enzyme activity by AST. In vivo studies showed an increase in G6PD, 6PGD, and GR enzyme activities (P Ëƒ 0.05) and no chance in TrxR enzyme activity by AST. Cd ion inhibited G6PD, 6PGD, and GR enzyme activities (P Ë‚ 0.05) and also decreased TrxR enzyme activity (P Ëƒ 0.05). AST + Cd group G6PD enzyme activity was statistically low compared with control group (P Ë‚ 0.05). 6PGD and TrxR enzyme activities decreased without statistical significance (P Ëƒ 0.05); however, GR enzyme activity increased statistically significantly (P Ë‚ 0.05).

Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.

Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination, and studies show that chemo-resistant carcinomas exhibit high levels of Rad51 expression. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Astaxanthin treatment (2.5-20 µM) decreased Rad51 expression and phospho-AKT(Ser473) protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector rescued the decreased Rad51 mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 or wortmannin) further decreased the Rad51 expression in astaxanthin-exposed A549 and H1703 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA or cotreatment with LY294002 further enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Additionally, mitomycin C (MMC) as an anti-tumor antibiotic is widely used in clinical NSCLC chemotherapy. Combination of MMC and astaxanthin synergistically resulted in cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced phospho-AKT(Ser473) level and Rad51 expression. Overexpression of AKT-CA or Flag-tagged Rad51 reversed the astaxanthin and MMC-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in astaxanthin and MMC co-treated cells. In conclusion, astaxanthin enhances MMC-induced cytotoxicity by decreasing Rad51 expression and AKT activation. These findings may provide rationale to combine astaxanthin with MMC for the treatment of NSCLC.

Review of genotoxicity and rat carcinogenicity investigations with astaxanthin.

Synthetic astaxanthin has been extensively tested for safety. Genotoxicity studies including Ames and in vitro Micronucleus Tests show absence of genotoxic potential. Although a long-term mouse study showed no carcinogenicity potential, the rat carcinogenicity study with dietary dosages of 0 (control), 0 (placebo beadlet), 40, 200 and 1000 mg astaxanthin/kg bw/day showed an increased incidence of benign, hepatocellular adenoma in females only, at 200 mg/kg bw/day and above. There was no clear evidence of toxicity during the in-life phase. Discoloration of feces was observed and a reduction in body weight gain in all groups receiving beadlets, probably reflecting a nutritional influence. Blood sampling confirmed systemic exposure and some minor clinical chemistry differences in females at 200 and 1000 mg/kg bw/day. There was no effect on adjusted liver weight. Histopathological examination showed hepatic changes indicative of slight hepatotoxicity and hepatocyte regeneration in females at 200 and 1000 mg/kg bw/day, in addition to the adenoma. Taking into account this pathological background in the female rat, and a wide variety of other supporting information, it is concluded that the hepatocellular adenoma in female rats was secondary to hepatotoxicity and regeneration, and is most probably a species-specific phenomenon of doubtful human relevance.

The cytotoxicity and cellular stress by temperature-fabricated polyshaped gold nanoparticles using marine macroalgae, Padina gymnospora.

Bioreduction of metal ions for the synthesis of stable nanoparticles (NPs) in physiological environment has been a great challenge in the field of nanotechnology and its application. In the present study, well-defined biofunctionalized gold nanoparticles (AuNPs) were developed following a biomimetic approach for an enhanced anticancer activity. The fucoxanthins-capped crystalline AuNPs showed a particle size of 14 nm. The temperature-mediated biosynthesized NPs were characterized by UV-vis, dynamic light scattering, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy. The cytotoxicity of the NPs was analyzed on liver (HepG2) and lung (A549) cancerous cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay infers that the biofunctionalized polyshaped AuNPs synthesized with an aqueous macroalgae extract showed a satisfactory anticancer effect on the cell lines, as evaluated by changes in cell morphology, cell viability, and metabolic activity. An altered cellular function and the morphology of cancer cell lines suggest a potential for in vivo application of AuNPs and the need to understand the interactions between nanomaterials, biomolecules, and cellular components. With continued improvements, these NPs may prove to be potential drug delivery vehicles for cancer therapy.

Fucoxantin: a treasure from the sea.

The World Health Organization (WHO) estimates that 2.3 billion people will be overweight and 700 million obese in 2015. The reasons for this disastrous trend are attributed to the global tendency toward the reduced magnitude of exercise and physical activity and the increased dietary intake of fats, sugars and calories with reduced amount of vitamins and minerals. To prevent life-style-related diseases, like Metabolic Syndrome (MS), researchers' attention is increasingly focusing on some of the so called "functional foods" which may be useful for their prevention and treatment. One of these functional ingredients is fucoxanthin (FX), a characteristic carotenoid present in edible brown seaweeds, such as Undaria pinnatifida (Wakame), Hijikia fusiformis (Hijiki), Laminaria japonica (Ma-Kombu) and Sargassum fulvellum. The increasing popularity of this molecule is certainly due to its anti-obesity effect, primarily detected by murine studies. These works revealed FX mediated induction of uncoupling protein-1 (UCP-1) in abdominal white adipose tissue (WAT) mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Beyond this important role, in recent studies FX has shown a great antioxidant activity, anti-cancer, anti-diabetic and anti-photoaging properties. The aim of this review is to highlight the main effects of FX on human health.

Use of lutein and zeaxanthin alone or combined with Brilliant Blue to identify intraocular structures intraoperatively.

PURPOSE: To determine whether a natural dye solution based on lutein and zeaxanthin alone or combined with Brilliant Blue stains and facilitates peeling of intraocular membranes in human eyes. METHODS: In this study of 60 cadaveric eyes, open-sky vitrectomy including posterior hyaloid detachment was performed. Different lutein and zeaxanthin concentrations (0.01-20%) were tested alone or combined with different Brilliant Blue concentrations (0.0125-0.025%) in the corneal endothelium, corneal epithelium, anterior and posterior capsule, vitreous cavity through the macula including the posterior hyaloid, and internal limiting membrane. The various dye solutions were in contact with the intraocular membranes for <1 minute and then were removed by mechanical aspiration or membrane peeling initiated and completed with intraocular forceps. The specimens were examined by light and electron transmission microscopy. RESULTS: Contact between lutein and zeaxanthin and the retinal, lens, and vitreous surface resulted in orange and greenish staining of the intraocular membranes, which facilitated surgical steps in all eyes. Lutein and zeaxanthin alone was useful for vitreous identification and lutein and zeaxanthin combined with Brilliant Blue had strong affinity for internal limiting membrane and anterior capsule. Light microscopy confirmed internal limiting membrane removal in all eyes tested. No dye solutions remained in the eyes after the membrane removal. CONCLUSION: A natural dye solution based on lutein and zeaxanthin alone or combined with Brilliant Blue efficiently stained the anterior capsule, vitreous, and internal limiting membrane in human cadaveric eyes and may be a useful tool for vitreoretinal or cataract surgery.

[Single and 13-week oral toxicity study of fucoxanthin oil from microalgae in rats].

Single oral dose and 13-week oral subchronic toxicity studies of fucoxanthin-containing oil extracted from microalga, Chaetoseros sp., were conducted in rats. In the single oral dose study, no mortality and no change related to the test material were observed. Thus, the 50% lethal dose of microalgal fucoxanthin oil is more than 2,000 mg/kg body weight. In the 13-week oral dose study, 0, 20 or 200 mg/kg body weight of microalgal fucoxanthin oil was administered. The fucoxanthin-administered groups, showed no mortality and no abnormalities. This result suggested that the no-observed-adverse-effect level of fucoxanthin-containing oil extracted from microalga Chaetoseros sp. was 200 mg/kg body weight under the tested subchronic dose condition.

[Bacterial reverse mutation test and micronucleus test of fucoxanthin oil from microalgae].

Fucoxanthin-containing oil extracted from microalga, Chaetoseros sp., was subjected to genotoxicity studies, the bacterial reverse mutation test and the micronucleus test in mice. The number of revertant colonies in fucoxanthin oil-treated plates of all strains tested was less than twice the number of colonies in the negative control, regardless of the presence of the metabolic activator in the bacterial reverse mutation test. In the micronucleus test, 500, 1,000, 2,000 mg/kg body weight of fucoxanthin oil was administered orally to mice. There was no significant increase in micronucleus frequency in bone marrow cells. These results suggest that fucoxanthin oil does not exhibit genotoxicity.