Effects of dietary nanoliposome-coated astaxanthin on haematological parameters, immune responses and the antioxidant status of rainbow trout (Oncorhynchus mykiss).

BACKGROUND: Astaxanthin is the most prevalent carotenoid in the marine environment and is widely used as an additive in formulated aquafeeds. OBJECTIVES: A 60-day feeding trial was conducted to consider the effect of dietary nanoliposome-coated astaxanthin (NA) on haematological parameters, serum antioxidant activities and immune responses of rainbow trout, Oncorhynchus mykiss. METHODS: A total of 450 healthy fish weighing 31.00 ± 2.09 g were randomly assigned in triplicate (30 fish per replicate) to 5 dietary treatments: 0 (control), 25.00, 50.00, 75.00, and 100.00 mg kg-1 NA. RESULTS: Fish fed the diet supplemented with 50.00 mg kg-1 NA exhibited the highest values of red blood cells, white blood cells, haemoglobin and haematocrit of 1.64 ± 0.01 × 106 mm-3, 5.54 ± 0.21 × 103 mm-3, 8.73 ± 0.24 g dL-1 and 46.67% ± 0.88%, respectively, which were significantly higher than those fed the basal diet (p < 0.05). The lowest and highest percentages of lymphocytes (67.67% ± 0.33%) and neutrophils (27.33% ± 1.20%) were also obtained in fish fed 50.00 mg kg-1 NA compared to those fed the basal diet (p < 0.05). Fish receiving diet supplemented with 50.00 mg kg-1 NA revealed the highest serum activity in superoxide dismutase, catalase, glutathione peroxidase, lysozyme and alternative complement and the lowest level of total cholesterol, cortisol, aspartate aminotransferase and alanine aminotransferase than fish receiving the basal diet (p < 0.05). Serum immunoglobulin (Ig) and ACH50 contents significantly increased with increasing dietary NA supplementation to the highest values of 43.17 ± 1.46 and 293.33 ± 2.03 U mL-1, respectively, in fish fed diet supplemented with 50 mg kg-1 NA (p < 0.05). CONCLUSIONS: Supplementation of NA in rainbow trout diet at 50 mg kg-1 exhibited a positive effect on haematological parameters, antioxidant capacity and immune responses. Administration of such dosage can enhance rainbow trout immune responses against unfavourable or stressful conditions, for example disease outbreaks, hypoxic condition, thermal stress and sudden osmotic fluctuations, which usually happen in an intensive culture system.

Astaxanthin, a Marine Carotenoid, Maintains the Tolerance and Integrity of Adipose Tissue and Contributes to Its Healthy Functions.

Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor's niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

The Beneficial Effects of Astaxanthin on Glucose Metabolism and Modified Low-Density Lipoprotein in Healthy Volunteers and Subjects with Prediabetes.

Astaxanthin (ASTX) is an antioxidant agent. Recently, its use has been focused on the prevention of diabetes and atherosclerosis. We examined the effects of astaxanthin supplementation for 12 weeks on glucose metabolism, glycemic control, insulin sensitivity, lipid profiles and anthropometric indices in healthy volunteers including subjects with prediabetes with a randomized, placebo-controlled trial. METHODS: We enrolled 53 subjects who met our inclusion criteria and administered them with 12 mg astaxanthin or a placebo once daily for 12 weeks. Subsequently, their HbA1c levels, lipid profiles and biochemical parameters were determined. The participants also underwent a 75 g oral glucose tolerance test (OGTT), vascular endothelial function test and measurement of the visceral fat area. RESULTS: After astaxanthin supplementation for 12 weeks, glucose levels after 120 min in a 75 g OGTT significantly decreased compared to those before supplementation. Furthermore, the levels of HbA1c (5.64 ± 0.33 vs. 5.57 ± 0.39%, p < 0.05), apo E (4.43 ± 1.29 vs. 4.13 ± 1.24 mg/dL, p < 0.05) and malondialdehyde-modified low-density lipoprotein (87.3 ± 28.6 vs. 76.3 ± 24.6 U/L, p < 0.05) were also reduced, whereas total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-C (HDL-C) levels were unaltered. The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. CONCLUSIONS: our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.

Systematic Review and Meta-Analysis on the Effects of Astaxanthin on Human Skin Ageing.

CONTEXT: Astaxanthin (ASX), a xanthophyll carotenoid derived from microalgae Haematococcus pluvialis, mitigating skin photoaging and age-related skin diseases by its antioxidant and anti-inflammatory effects in animal studies. OBJECTIVE: The aim was to systematically evaluate if ASX applications have anti-ageing effects in humans. METHODS: A comprehensive search of PubMed, Scopus and Web of Science found a total of eleven studies. Nine randomised, controlled human studies assessed oral ASX effects and two open-label, prospective studies evaluated topical, oral-topical ASX effects on skin ageing. GetData Graph Digitizer was used to extract mean values and standard deviations of baseline and endpoint, and Cochrane Collaboration's tool assessed RoB for all included studies. Review Manager 5.4 was used to conduct meta-analysis of RCTs; the results were reported as effect size ± 95% confidence interval. RESULTS: Oral ASX supplementation significantly restored moisture content (SMD = 0.53; 95% CI = 0.05, 1.01; I2 = 52%; p = 0.03) and improved elasticity (SMD = 0.77; 95% CI = 0.19, 1.35; I2 = 75%; p = 0.009) but did not significantly decrease wrinkle depth (SMD = -0.26; 95% CI = -0.58, 0.06; I2 = 0%; p = 0.11) compared to placebo. Open-label, prospective studies suggested slightly protective effects of topical and oral-topical ASX applications on skin ageing. CONCLUSIONS: Ingestion and/or topical usages of ASX may be effective in reducing skin ageing and have promising cosmetical potential, as it improves moisture content and elasticity and reduces wrinkles.

Dietary astaxanthin augments disease resistance of Asian seabass, Lates calcarifer (Bloch, 1790), against Vibrio alginolyticus infection.

This investigation describes the impacts of dietary provisioning with astaxanthin on hemato-biochemistry, non-specific immunity, and disease resistance of the Asian seabass, Lates calcarifer, against the virulent Vibrio alginolyticus; with specific reference to dose-response associations and variations over different post-infection periods (0-, 7-, and 14-day). Triplicate groups of fish weighing 28 g, on average, were fed various diets (C, the control or astaxanthin-free; AXT50, 50 mg astaxanthin kg-1 diet; AXT100, 100 mg astaxanthin kg-1 diet; and AXT150, 150 mg astaxanthin kg-1 diet) for 90 days and subsequently challenged with V. alginolyticus at the end of the feeding period. Experimental infection unveiled that supplemented fish demonstrated significant improvements (P < 0.05) of hematological parameters (white blood cell [WBC] and red blood cell [RBC] counts, and hemoglobin and hematocrit levels) when fed diets with elevating supplemental doses of astaxanthin through distinct post-infection periods (0-, 7-, and 14-day). Furthermore, the administration of dietary astaxanthin at escalating levels markedly enhanced (P < 0.05) the serum biochemical profile (aspartate aminotransferase [AST], alanine aminotransferase [ALT], glucose, cortisol, cholesterol, and triglyceride contents) of challenged fish, resulting in better welfare. Significantly higher (P < 0.05) contents of serum total protein were observed in supplemented fish, as opposed to the control. Additionally, immunological defense mechanisms (lysozyme activity, phagocytic activity, respiratory burst activity, and total serum immunoglobulin) of challenged fish were pronouncedly elicited (P < 0.05) following the ingestion of astaxanthin. Besides, the supplementation with dietary astaxanthin significantly augmented (P < 0.05) the post-challenge survival rate of fish. Collectively, the results manifest that supplementary feeding of astaxanthin is effective in reinforcing fish immunocompetence and disease resistance against V. alginolyticus infection.

A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration.

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.

Astaxanthin Z-isomer-rich diets enhance egg yolk pigmentation in laying hens compared to that in all-E-isomer-rich diets.

The effects of feeding diets containing astaxanthin with different Z-isomer ratios to laying hens on egg qualities, such as astaxanthin concentration in egg yolk and yolk color, were investigated. As the astaxanthin source, a natural microorganism Paracoccus carotinifaciens was used. Astaxanthin with different Z-isomer ratios was prepared by thermal treatment with different conditions and then added to the basal diet at a final astaxanthin concentration of 8 mg/kg. We found that, as the Z-isomer ratios of astaxanthin in the diet increased, the astaxanthin concentration in egg yolk and the yolk color fan score also increased significantly. Importantly, feeding a 50.6% Z-isomer ratio diet increased astaxanthin concentration in egg yolk by approximately fivefold and the color fan score by approximately 2 compared to that in hens fed an all-E-isomer-rich diet. Moreover, we showed that feeding Z-isomer-rich astaxanthin to laying hens increased plasma astaxanthin concentration by more than five times in comparison to that in hens fed an all-E-isomer-rich diet. These results indicate that Z-isomers of astaxanthin have higher bioavailability than that of the all-E-isomer and thus they exhibit greater egg yolk-accumulation efficiency.

Fucoxanthin extracted from Laminaria Japonica inhibits metastasis and enhances the sensitivity of lung cancer to Gefitinib.

ETHNOPHARMACOLOGICAL RELEVANCE: Laminaria japonica, a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including lung cancer. AIM OF THE STUDY: To demonstrate the effects of Fucoxanthin (FX), a major active component extracted from Laminaria japonica on metastasis and Gefitinib (Gef) sensitivity in human lung cancer cells both in vitro and in vivo. MATERIALS AND METHODS: Invasion and migration of lung cancer cells were detected using the wound healing assay and transwell assay. Epithelial-to-mesenchymal transition (EMT) factors and PI3K/AKT/NF-κB pathways were analyzed by western blotting. RNA interference (RNAi) technology was used to silence TIMP-2 gene expression in A549 cells. The anti-metastatic effect of FX was evaluated in vivo in an experimental lung metastatic tumor model. On the other hand, cell counting kit-8 assay was used to study the cell viability of human lung cancer PC9 cells and Gef resistant PC9 cells (PC9/G) after Gef, FX or FX combined with Gef treatment. PC9 xenograft model was established to explore the anti-tumor effect of FX or combined with Gef. Immunohistochemistry staining assay and immunofluorescence staining assay were used to reveal the effects of FX on lung cancer cell proliferation and apoptosis. RESULTS: FX was able to significantly inhibit lung cancer cells migration and invasion in vitro. FX suppressed the expressions of Snail, Twist, Fibronectin, N-cadherin, MMP-2, PI3K, p-AKT and NF-κB, and increased the expression of TIMP-2. Furthermore, knockdown of TIMP-2 attenuated FX-mediated invasion inhibition. Additionally, we demonstrated that FX inhibited lung cancer cells metastasis in vivo. The anti-metastatic effects of FX on lung cancer cells might be attributed to inhibition of EMT and PI3K/AKT/NF-κB pathway. We further demonstrated that the anti-tumor activity of FX was not only limited to the drug sensitive cell lines, but also prominent on lung cancer cells with Gef resistant phenotype. Furthermore, in vivo xenograft assay confirmed that FX inhibited tumor growth and enhanced the sensitivity of lung cancer cells to Gef and this effect may be due to inhibition of tumor cell proliferation and activation of apoptosis. CONCLUSION: Collectively, our findings suggested that FX suppresses metastasis of lung cancer cells and overcomes EGFR TKIs resistance. Thus, FX is worthy of further investigation as a drug candidate for the treatment of lung cancer.

The effect of astaxanthin supplementation on performance and fat oxidation during a 40 km cycling time trial.

OBJECTIVES: This study aimed to investigate whether supplementation with 12 mg⋅day-1 astaxanthin for 7 days can improve exercise performance and metabolism during a 40 km cycling time trial. DESIGN: A randomised, double-blind, crossover design was employed. METHODS: Twelve recreationally trained male cyclists (VO2peak: 56.5 ± 5.5 mL⋅kg-1⋅min-1, Wmax: 346.8  ± 38.4 W) were recruited. Prior to each experimental trial, participants were supplemented with either 12 mg⋅day-1 astaxanthin or an appearance-matched placebo for 7 days (separated by 14 days of washout). On day 7 of supplementation, participants completed a 40 km cycling time trial on a cycle ergometer, with indices of exercise metabolism measured throughout. RESULTS: Time to complete the 40 km cycling time trial was improved by 1.2 ± 1.7% following astaxanthin supplementation, from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the astaxanthin condition (mean improvement = 51 ± 71 s, p = 0.029, g = 0.21). Whole-body fat oxidation rates were also greater (+0.09 ± 0.13 g⋅min-1, p = 0.044, g = 0.52), and the respiratory exchange ratio lower (-0.03 ± 0.04, p = 0.024, g = 0.60) between 39-40 km in the astaxanthin condition. CONCLUSIONS: Supplementation with 12 mg⋅day-1 astaxanthin for 7 days provided an ergogenic benefit to 40 km cycling time trial performance in recreationally trained male cyclists and enhanced whole-body fat oxidation rates in the final stages of this endurance-type performance event.

Improvement of Executive Function after Short-Term Administration of an Antioxidants Mix Containing Bacopa, Lycopene, Astaxanthin and Vitamin B12: The BLAtwelve Study.

During the last few years increasing interest has been focused on antioxidants as potentially useful agents in the prevention of the onset and progression of cognitive dysfunction. In this randomized, double-blind, controlled, parallel arm study, the effects of daily consumption of an antioxidant mix on cognitive function in healthy older adults were evaluated. After a 1 week run-in period, 80 subjects aged 60 years or more, and with no evidence of cognitive dysfunction, were randomly allocated to a mix of four bioactive compounds (bacopa, lycopene, astaxanthin, and vitamin B12) or matched placebo, taken orally once a day for 8 weeks. The primary objective of the study was to evaluate the changes in trial making test (TMT) scores from baseline to 8 weeks of treatment, analyzed in the following hierarchical order: TMT-B, TMT-A, and TMT-B minus TMT-A. TMT-B increased in the control group (+3.46 s) and decreased in the active group (-17.63 s). The treatment difference was -21.01 s in favor of the active group (95% C.I. -26.80 to -15.2, p < 0.0001). The decrease in TMT-A was significantly higher in the active group (-6.86 s) than in the control group (-0.37 s). TMT-B minus TMT-A increased in the control group (+3.84 s) and decreased in the active group (-10.46 s). The increase in letter fluency in the verbal fluency test (VFT) was also significantly higher in the active group and statistically significant (+5.28 vs. +1.07 words; p < 0.001). Our findings provide encouraging evidence that regular dietary supplementation with bacopa, lycopene, astaxanthin, and vitamin B12 may be an effective dietary approach for counteracting cognitive changes associated with brain aging.

Fucoxanthin activities motivate its nano/micro-encapsulation for food or nutraceutical application: a review.

Fucoxanthin is a xanthophyll carotenoid abundant in marine brown algae. The potential therapeutic effects of fucoxanthin on tumor intervention have been well documented, which have aroused great interests in utilizing fucoxanthin in functional foods and nutraceuticals. However, the utilization of fucoxanthin as a nutraceutical in food and nutrient supplements is currently limited due to its low water solubility, poor stability, and limited bioaccessibility. Nano/micro-encapsulation is a technology that can overcome these challenges. A systematic review on the recent progresses in nano/micro-delivery systems to encapsulate fucoxanthin in foods or nutraceuticals is warranted. This article starts with a brief introduction of fucoxanthin and the challenges of oral delivery of fucoxanthin. Nano/micro-encapsulation technology is then covered, including materials and strategies for constructing the delivery system. Finally, future prospective has been discussed on properly designed oral delivery systems of fucoxanthin for managing cancer. Natural edible materials such as whey protein, casein, zein, gelatin, and starch have been successfully utilized to fabricate lipid-based, gel-based, or emulsion-based delivery systems, molecular nanocomplexes, and biopolymer nanoparticles with the aid of advanced processing techniques, such as freeze-drying, high pressure homogenization, sonication, anti-solvent precipitation, coacervation, ion crosslinking, ionic gelation, emulsification, and enzymatic conjugation. These formulated nano/micro-capsules have proven to be effective in stabilizing and enhancing the bioaccessibility of fucoxanthin. This review will inspire a surge of multidisciplinary research in a broader community of foods and motivate material scientists and researchers to focus on nano/micro-encapsulated fucoxanthin in order to facilitate the commercialization of orally-deliverable tumor intervention products.

Properties of Carotenoids in Fish Fitness: A Review.

Carotenoids, one of the most common types of natural pigments, can influence the colors of living organisms. More than 750 kinds of carotenoids have been identified. Generally, carotenoids occur in organisms at low levels. However, the total amount of carotenoids in nature has been estimated to be more than 100 million tons. There are two major types of carotenoids: carotene (solely hydrocarbons that contain no oxygen) and xanthophyll (contains oxygen). Carotenoids are lipid-soluble pigments with conjugated double bonds that exhibit robust antioxidant activity. Many carotenoids, particularly astaxanthin (ASX), are known to improve the antioxidative state and immune system, resulting in providing disease resistance, growth performance, survival, and improved egg quality in farmed fish without exhibiting any cytotoxicity or side effects. ASX cooperatively and synergistically interacts with other antioxidants such as α-tocopherol, ascorbic acid, and glutathione located in the lipophilic hydrophobic compartments of fish tissue. Moreover, ASX can modulate gene expression accompanying alterations in signal transduction by regulating reactive oxygen species (ROS) production. Hence, carotenoids could be used as chemotherapeutic supplements for farmed fish. Carotenoids are regarded as ecologically friendly functional feed additives in the aquaculture industry.

Inflammation response after the cessation of chronic arsenic exposure and post-treatment of natural astaxanthin in liver: potential role of cytokine-mediated cell-cell interactions.

Ongoing groundwater arsenic contamination throughout China was first recognized in the 1960s. Groundwater arsenic contamination is a high risk for human and animal health worldwide. Apart from drinking water, diet is the second pathway for arsenic to enter the human body and eventually cause liver injury. Natural astaxanthin extracted from the green algae Haematococcus pluvialis has dominated the nutraceutical market for potential health benefits. Nevertheless, the molecular mechanism underlying the protective effect post astaxanthin against arsenic-induced hepatotoxicity remains largely obscure. In this study, we investigate the effect of natural astaxanthin (derived from Haemotococcus pluvialis) on oxidative stress and liver inflammatory response in rats after the cessation of chronic arsenic exposure. Wistar rats were given astaxanthin (250 mg kg-1) daily for 2 weeks after the cessation of exposure to sodium arsenite (300 µg L-1, drinking water, 24 weeks) by intragastric administration. The results showed that post treatment with astaxanthin attenuated liver injury induced by long-term exposure to arsenic in rats. Most importantly, post treatment with astaxanthin decreased the increasing of inflammatory cytokine NF-κB, tumor necrosis factor-α, interleukin-1ß, oxidative stress level, and total arsenic content in livers of rats exposed to arsenic. In addition, post treatment with astaxanthin reversed the increasing of protein levels of alpha-smooth muscle actin and collagen Iα1, which are the activation markers of hepatic stellate cells (HSCs). Collectively, these data demonstrate that post astaxanthin treatment attenuates inflammation response in the liver after the cessation of chronic arsenic exposure via inhibition of cytokine-mediated cell-cell interactions. Daily ingestion of natural astaxanthin might be a potential and beneficial candidate for the treatment of liver damage after the cessation of chronic exposure to sodium arsenite.

Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells.

Pathway analysis is an informative method for comparing and contrasting drug-induced gene expression in cellular systems. Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, on gene expression in a well-established human glioblastoma cell system, U87MG. Under conditions which inhibit cell proliferation, LY-294002 and fucoxanthin modulate many pathways in common, including the retinoblastoma, DNA damage, DNA replication and cell cycle pathways. In sharp contrast, we see profound differences in the expression of genes characteristic of pathways such as apoptosis and lipid metabolism, contributing to the development of a differentiated and distinctive drug-induced gene expression signature for each compound. Furthermore, in combination, fucoxanthin synergizes with LY-294002 in inhibiting the growth of U87MG cells, suggesting complementarity in their molecular modes of action and pointing to further treatment combinations. The synergy we observe between the dietary nutraceutical fucoxanthin and the synthetic chemical LY-294002 in producing growth arrest in glioblastoma, illustrates the potential of nutri-pharmaceutical combinations in targeting this challenging disease.

Astaxanthin-Shifted Gut Microbiota Is Associated with Inflammation and Metabolic Homeostasis in Mice.

BACKGROUND: Astaxanthin is a red lipophilic carotenoid that is often undetectable in human plasma due to the limited supply in typical Western diets. Despite its presence at lower than detectable concentrations, previous clinical feeding studies have reported that astaxanthin exhibits potent antioxidant properties. OBJECTIVE: We examined astaxanthin accumulation and its effects on gut microbiota, inflammation, and whole-body metabolic homeostasis in wild-type C57BL/6 J (WT) and ß-carotene oxygenase 2 (BCO2) knockout (KO) mice. METHODS: Six-wk-old male and female BCO2 KO and WT mice were provided with either nonpurified AIN93M (e.g., control diet) or the control diet supplemented with 0.04% astaxanthin (wt/wt) ad libitum for 8 wk. Whole-body energy expenditure was measured by indirect calorimetry. Feces were collected from individual mice for short-chain fatty acid assessment. Hepatic astaxanthin concentrations and liver metabolic markers, cecal gut microbiota profiling, inflammation markers in colonic lamina propria, and plasma samples were assessed. Data were analyzed by 3-way ANOVA followed by Tukey's post hoc analysis. RESULTS: BCO2 KO but not WT mice fed astaxanthin had ∼10-fold more of this compound in liver than controls (P < 0.05). In terms of the microbiota composition, deletion of BCO2 was associated with a significantly increased abundance of Mucispirillum schaedleri in mice regardless of gender. In addition to more liver astaxanthin in male KO compared with WT mice fed astaxanthin, the abundance of gut Akkermansia muciniphila was 385% greater, plasma glucagon-like peptide 1 was 27% greater, plasma glucagon and IL-1ß were 53% and 30% lower, respectively, and colon NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation was 23% lower (all P < 0.05) in male KO mice than the WT mice. CONCLUSIONS: Astaxanthin affects the gut microbiota composition in both genders, but the association with reductions in local and systemic inflammation, oxidative stress, and improvement of metabolic homeostasis only occurs in male mice.

The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes.

BACKGROUND: Multidrug resistance (MDR) causes failure of doxorubicin therapy of cancer cells, which develops after or during doxorubicin treatment resulting in cross-resistance to structurally and functionally-unrelated other anticancer drugs. MDR is multifactorial phenomenon associated with overexpression of ATP-binding cassette (ABC) transporters, metabolic enzymes, impairment of apoptosis, and alteration of cell cycle checkpoints. The cancer-prevention of the dietary carotenoid; fucoxanthin (FUC) has been extensively explored. Nevertheless, the underlying mechanism of its action is not full elucidated. HYPOTHESIS/PURPOSE: Investigation of the underlying mechanism of MDR reversal by the dietary carotenoid fucoxanthin (FUC) and its ability to enhance the doxorubicin (DOX) cytotoxicity in resistant breast (MCF-7/ADR), hepatic (HepG-2/ADR), and ovarian (SKOV-3/ADR) cell lines. METHODS: The synergistic interaction of FUC and DOX was evaluated using several techniques, viz.; MTT assay, ABC transporter function assays using FACS and fluorimetry, enzyme activity via spectroscopy and luminescence assays, and apoptosis assay using FACS, and gene expression using RTPCR. RESULTS: FUC (20 µM) synergistically enhanced the cytotoxicity of DOX and significantly reduced the dose of DOX (FR) in DOX resistant cells (MCF-7/ADR), hepatic (HepG-2/ADR), and ovarian (SKOV-3/ADR) to 8.42-(CI= 0.25), 6.28-(CI= 0.32), and 4.56-fold (CI=0.37) (P<0.001). FUC significantly increased the accumulation of DOX more than verapamil in resistant cells by 2.70, 2.67, and 3.95-fold of untreated cells (p<0.001), respectively. A FUC and DOX combination significantly increased the Rho123 accumulation higher than individual drugs by 2.36-, 2.38-, 1.89-fold verapamil effects in tested cells (p<0.001), respectively. The combination of the FUC and DOX decreased ABCC1, ABCG2, and ABCB1 expression. The FUC and DOX combination increased the levels and activity of caspases (CASP3, CASP8) and p53, while decreased the levels and activity of CYP3A4, GST, and PXR in resistant cancer cells. The combination induced early/late apoptosis to 91.9/5.4% compared with 0.0/0.7% of untreated control. CONCLUSION: Our data suggests a new dietary and therapeutic approach of combining the FUC with DOX to overcome multidrug resistance in cancer cells. However, animal experiments should be conducted to confirm the findings before applying the results into clinical trials.

Effects of 3-Month Astaxanthin Supplementation on Cardiac Function in Heart Failure Patients with Left Ventricular Systolic Dysfunction-A Pilot Study.

Astaxanthin has strong antioxidant properties. We conducted a prospective pilot study on heart failure (HF) patients with left ventricular (LV) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation. Oxidative stress markers-serum Diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, LV ejection fraction (LVEF), and 6-min walk distance (6MWD) were assessed before and after 3-month astaxanthin supplementation. Finally, the data of 16 HF patients were analyzed. Following 3-month astaxanthin supplementation, dROM level decreased from 385.6 ± 82.6 U.CARR to 346.5 ± 56.9 U.CARR (p = 0.041) despite no changes in BAP and urinary 8-OHdG levels. LVEF increased from 34.1 ± 8.6% to 38.0 ± 10.0% (p = 0.031) and 6MWD increased from 393.4 ± 95.9 m to 432.8 ± 93.3 m (p = 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF. In this study, following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance were observed in HF patients with LV systolic dysfunction. Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning.

Transcriptome analysis reveals the potential mechanism of dietary carotenoids improving antioxidative capability and immunity of juvenile Chinese mitten crabs Eriocheir sinensis.

Carotenoids are known to be involved in the regulation of the antioxidative capability, immune response and stress resistance in crustacean species; however, very limited information is available on their underlying molecular mechanisms. This study performed transcriptome sequencing of hemolymph and hepatopancreas of juvenile Chinese mitten crabs (Eriocheir sinensis) that fed with three diets, i.e. diet A containing 90 mg kg-1 dry weight of astaxanthin, diet B containing 200 mg kg-1 dry weight of ß-carotene and control diet without supplementation of dietary carotenoids. The results showed that there were 2955 and 497 differentially expressed genes (DEGs) in the hemolymph between the astaxanthin treatment and control groups, and between the ß-carotene treatment and control groups, respectively. Moreover, compared with the control group, 833 and 1886 DEGs were obtained in the hepatopancreas of the astaxanthin treatment and the ß-carotene treatment groups, respectively. The DEGs in the three groups were enriched in 255 specific KEGG metabolic pathways according to KEGG enrichment analysis. Through this study, a series of key genes involved in Nrf2 signalling, ROS production, intracellular antioxidant enzymes and chaperones were significantly affected by dietary carotenoids. Dietary carotenoids also significantly altered the expression levels of immune-related molecules associated with signal transduction, prophenoloxidase cascade, apoptosis, pattern recognition proteins/receptors and antimicrobial peptides. In conclusion, this transcriptomic study provides valuable information for understanding the molecular mechanism and potential pathway of dietary carotenoids improved the antioxidative capability and immunity of juvenile E. sinensis.

Clinical Applications of Astaxanthin in the Treatment of Ocular Diseases: Emerging Insights.

Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls, and is typically found in marine environments, especially in microalgae and seafood such as salmonids, shrimps and lobsters. Due to its unique molecular structure, astaxanthin features some important biologic properties, mostly represented by strong antioxidant, anti-inflammatory and antiapoptotic activities. A growing body of evidence suggests that astaxanthin is efficacious in the prevention and treatment of several ocular diseases, ranging from the anterior to the posterior pole of the eye. Therefore, the present review aimed at providing a comprehensive evaluation of current clinical applications of astaxanthin in the management of ocular diseases. The efficacy of this carotenoid in the setting of retinal diseases, ocular surface disorders, uveitis, cataract and asthenopia is reported in numerous animal and human studies, which highlight its ability of modulating several metabolic pathways, subsequently restoring the cellular homeostatic balance. To maximize its multitarget therapeutic effects, further long-term clinical trials are warranted in order to define appropriate dosage, route of administration and exact composition of the final product.

Siphonaxanthin, a carotenoid from green algae Codium cylindricum, protects Ob/Ob mice fed on a high-fat diet against lipotoxicity by ameliorating somatic stresses and restoring anti-oxidative capacity.

Oxidative stress is implicated in the pathogenesis of many diseases including obesity, non-alcoholic fatty liver disease, and diabetes mellitus. Previously, we reported that siphonaxanthin, a carotenoid from green algae, elicited a potent inhibitory effect on hepatic de novo lipogenesis, and an anti-obesity effect in both 3T3L1 cells and KKAy mice. Thus, we hypothesized that consumption of siphonaxanthin could improve metabolic disorders including hepatic steatosis and systemic adiposity, as well as ameliorate somatic stress under obese conditions. Both the hepatocyte cell line HepG2 and a mouse model of severe obesity, produced by feeding Ob/Ob mice on a high-fat diet (HFD), were used to test this hypothesis. In obese mice, siphonaxanthin intake did not improve liver steatosis or systemic adiposity. However, intake did lower plasma glucose and alanine aminotransferase (ALT) levels and diminished hepatic lipid peroxidation products and antioxidant gene expression, which increased significantly in control group obese mice. Renal protein carbonyl content decreased significantly in the siphonaxanthin group, which might also indicate an ameliorated oxidative stress. Siphonaxanthin restored gene expression related to antioxidant signaling, lipid ß-oxidation, and endoplasmic-reticulum-associated protein degradation in the kidney, which decreased significantly in obese mice. Liver and kidney responded to obesity-induced somatic stress in a divergent pattern. In addition, we confirmed that siphonaxanthin potently induced Nrf2-regulated antioxidant signaling in HepG2 cells. In conclusion, our results indicated that siphonaxanthin might protect obesity-leading somatic stress through restoration of Nrf2-regulated antioxidant signaling, and might be a promising nutritional supplement.