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.

Fucoxanthin restructures the gut microbiota and metabolic functions of non-obese individuals in an in vitro fermentation model.

Fucoxanthin, a carotenoid exclusively derived from algae, exerts its bioactivities with the modulation of the gut microbiota in mice. However, mechanisms through which fucoxanthin regulates the gut microbiota and its derived metabolites/metabolism in humans remain unclear. In this study, we investigated the effects of fucoxanthin on the gut microbiota and metabolism of non-obese individuals using an in vitro simulated digestion-fermentation cascade model. The results showed that about half of the fucoxanthin was not absorbed in the intestine, thus reaching the colon. The gut microbiota from fecal samples underwent significant changes after 48 or 72 hours in vitro fermentation. Specifically, fucoxanthin significantly enhanced the relative abundance of Bacteroidota and Parabacteroides, leading to improved functions of the gut microbiota in its development, glycan biosynthesis and metabolism as well as in improving the digestive system, endocrine system and immune system. The recovery of fucoxanthin during fermentation showed a decreasing trend with the slight bio-conversion of fucoxanthinol. Notably, fucoxanthin supplementation significantly altered metabolites, especially bile acids and indoles in the simulated human gut ecosystem. Correlation analysis indicated the involvement of the gut microbiota in the manipulation of these metabolites by fucoxanthin. Moreover, all these altered metabolites revealed the improvement in the capacity of fucoxanthin in manipulating gut metabolism, especially lipid metabolism. Overall, fucoxanthin determinedly reshaped the gut microbiota and metabolism, implying its potential health benefits in non-obese individuals.

Astaxanthin Ameliorates Skeletal Muscle Atrophy in Mice With Cancer Cachexia.

Astaxanthin (AST) is a natural marine carotenoid with a variety of biological activities. This study aimed to demonstrate the possible mechanisms by which AST improves skeletal muscle atrophy in cancer cachexia. In this study, the effects of different doses of AST (30 mg/kg b.w., 60 mg/kg b.w. and 120 mg/kg b.w.) on skeletal muscle functions were explored in mice with cancer cachexia. The results showed that AST (30, 60 and 120 mg/kg b.w.) could effectively protect cachexia mice from body weight and skeletal muscle loss. AST dose-dependently ameliorated the decrease in myofibres cross-sectional area and increased the expression of myosin heavy chain (MHC). AST treatment decreased both the serum and muscle level of IL-6 but not TNF-α in C26 tumor-bearing cachexia mice. Moreover, AST alleviated skeletal muscle atrophy by decreasing the expression of two muscle-specific E3 ligases MAFBx and MuRF-1. AST improved mitochondrial function by downregulating the levels of muscle Fis1, LC3B and Bax, upregulating the levels of muscle Mfn2 and Bcl-2. In conclusion, our study show that AST might be expected to be a nutritional supplement for cancer cachexia patients.

The Effects of Astaxanthin on Cognitive Function and Neurodegeneration in Humans: A Critical Review.

Oxidative stress is a key contributing factor in neurodegeneration, cognitive ageing, cognitive decline, and diminished cognitive longevity. Issues stemming from oxidative stress both in relation to cognition and other areas, such as inflammation, skin health, eye health, and general recovery, have been shown to benefit greatly from antioxidant use. Astaxanthin is a potent antioxidant, which has been outlined to be beneficial for cognitive function both in vitro and in vivo. Given the aforementioned promising effects, research into astaxanthin with a focus on cognitive function has recently been extended to human tissue and human populations. The present critical review explores the effects of astaxanthin on cognitive function and neurodegeneration within human populations and samples with the aim of deciphering the merit and credibility of the research findings and subsequently their potential as a basis for therapeutic use. Implications, limitations, and areas for future research development are also discussed. Key findings include the positive impacts of astaxanthin in relation to improving cognitive function, facilitating neuroprotection, and slowing neurodegeneration within given contexts.

Astaxanthin targets IL-6 and alleviates the LPS-induced adverse inflammatory response of macrophages.

Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and the modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharides (LPS) served as inflammatory stimuli. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPSs escalated the expression of inflammation-related molecules. Our results demonstrate that AST intervention could effectively alleviate LPS-induced oxidative stress, facilitate cellular repair, and significantly attenuate inflammation. Further exploration of the anti-inflammatory mechanism revealed AST could substantially inhibit NF-κB translocation and activation, and mitigate inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as a popular dietary supplement of anti-inflammatory or immunomodulatory function.

Recent progress in practical applications of a potential carotenoid astaxanthin in aquaculture industry: a review.

Astaxanthin is the main natural C40 carotenoid used worldwide in the aquaculture industry. It normally occurs in red yeast Phaffia rhodozyma and green alga Haematococcus pluvialis and a variety of aquatic sea creatures, such as trout, salmon, and shrimp. Numerous biological functions reported its antioxidant and anti-inflammatory activities since astaxanthin possesses the highest oxygen radical absorbance capacity (ORAC) and is considered to be over 500 more times effective than vitamin E and other carotenoids such as lutein and lycopene. Thus, synthetic and natural sources of astaxanthin have a commanding influence on industry trends, causing a wave in the world nutraceutical market of the encapsulated product. In vitro and in vivo studies have associated astaxanthin's unique molecular features with various health benefits, including immunomodulatory, photoprotective, and antioxidant properties, providing its chemotherapeutic potential for improving stress tolerance, disease resistance, growth performance, survival, and improved egg quality in farmed fish and crustaceans without exhibiting any cytotoxic effects. Moreover, the most evident effect is the pigmentation merit, where astaxanthin is supplemented in formulated diets to ameliorate the variegation of aquatic species and eventually product quality. Hence, carotenoid astaxanthin could be used as a curative supplement for farmed fish, since it is regarded as an ecologically friendly functional feed additive in the aquaculture industry. In this review, the currently available scientific literature regarding the most significant benefits of astaxanthin is discussed, with a particular focus on potential mechanisms of action responsible for its biological activities.

Fucoxanthin exert dose-dependent antifibrotic and anti-inflammatory effects on CCl4-induced liver fibrosis.

The lack of an effective non-surgical liver fibrosis treatment is a major problem in hepatology. Fucoxanthin is a marine xanthophyll that exhibits anti-inflammatory, antioxidant, and hepatoprotective properties, thereby indicating its potential effectiveness in the treatment of liver fibrosis. The study aims to investigate the antifibrotic and anti-inflammatory effects of fucoxanthin and its main mechanisms on carbon tetrachloride (CCl4)-induced liver fibrosis in 50 outbred ICR/CD1 mice. 2 µl/g of CCl4 were injected intraperitoneally 2 times a week for 6 weeks. Fucoxanthin (5, 10, 30 mg/kg) was administered via gavage. Liver histopathology was evaluated by Hematoxylin-Eosin (H&E) and Sirius Red staining using the METAVIR scale. The immunohistochemical method was used to determine the number of CD45 and α-smooth muscle actin (α-SMA) positive cells, and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and α-SMA positive areas. Using enzyme immunoassays, procollagen 1 (COL1A1), transforming growth factor-ß (TGF-ß), and hepatocyte growth factor (HGF) were determined in homogenate, and interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were determined in blood serum. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activity, albumin (ALB), and total bilirubin (Tbil) levels are determined by biochemical assays. Fucoxanthin significantly reduced the severity of liver fibrosis, profibrogenic markers, inflammatory infiltration, and pro-inflammatory cytokines. In summary, we confirmed that fucoxanthin has a dose-dependent antifibrotic effect on CCl4-induced liver fibrosis. We found that the anti-inflammatory effect of fucoxanthin is related to the inhibition of IL-1ß and TNF-α synthesis, as well as the decrease in the number of leukocytes in the injured liver.

Potent carotenoid astaxanthin expands the anti-cancer activity of cisplatin in human prostate cancer cells.

Prostate cancer (PCa) is the second most common type of cancer and the sixth cause of death in men worldwide. Radiotherapy and immunotherapy are commonly used in treating PCa, but understanding the crosstalk mechanisms of carcinogenesis and new therapeutic approaches is essential for supporting poor diagnosis and existing therapies. Astaxanthin (ASX) is a member of the xanthophyll family that is an oxygenated derivative of carotenoids whose synthesis is in plant extracts from lycopene. ASX has protective effects on various diseases, such as Parkinson's disease and cancer by showing potent antioxidant and anti-inflammatory properties. However, there is an ongoing need for a detailed investigation of the molecular mechanism of action to expand its therapeutic use. In the present study, we showed the new regulatory role of ASX in PCa cells by affecting the unfolded protein response (UPR) signaling, autophagic activity, epithelial-mesenchymal transition (EMT) and regulating the expression level of angiogenesis-related protein vascular endothelial growth factor A (VEGF-A), proto-oncogene c-Myc and prostate-specific antigen (PSA). Additionally, we determined that it exhibited synergistic action with cisplatin and significantly enhanced apoptotic cell death in PCa cells. Present findings suggest that ASX may be a potent adjuvant therapeutic option in PCa treatment when used alone or combined with chemotherapeutics. Schematic illustration of the biochemical activity of astaxanthin and its combination with cisplatin.

Production and therapeutic use of astaxanthin in the nanotechnology era.

Astaxanthin (AXT) is a red fat-soluble pigment found naturally in aquatic animals, plants, and various microorganisms and can be manufactured artificially using chemical catalysis. AXT is a xanthophyll carotenoid with a high potential for scavenging free radicals. Several studies have investigated AXT efficacy against diseases such as neurodegenerative, ocular, skin, and cardiovascular hypertension, diabetes, gastrointestinal and liver diseases, and immuno-protective functions. However, its poor solubility, low stability to light and oxygen, and limited bioavailability are major obstacles hindering its wide applications as a therapeutic agent or nutritional supplement. Incorporating AXT with nanocarriers holds great promise in enhancing its physiochemical properties. Nanocarriers are delivery systems with several benefits, including surface modification, bioactivity, and targeted medication delivery and release. Many approaches have been applied to enhance AXT's medicinal effect, including solid lipid nanoparticles, nanostructured lipid carriers (NLCs) and polymeric nanospheres. AXT nano-formulations have demonstrated a high antioxidant and anti-inflammatory effect, significantly affecting cancer in different organs. This review summarizes the most recent data on AXT production, characterization, biological activity, and therapeutic usage, focusing on its uses in the nanotechnology era.

Skeletonema marinoi Extracts and Associated Carotenoid Fucoxanthin Downregulate Pro-Angiogenic Mediators on Prostate Cancer and Endothelial Cells.

The exploration of natural preventive molecules for nutraceutical and pharmaceutical use has recently increased. In this scenario, marine microorganisms represent an underestimated source of bioactive products endowed with beneficial effects on health that include anti-oxidant, anti-inflammatory, differentiating, anti-tumor, and anti-angiogenic activities. Here, we tested the potential chemopreventive and anti-angiogenic activities of an extract from the marine coastal diatom Skeletonema marinoi Sarno and Zingone (Sm) on prostate cancer (PCa) and endothelial cells. We also tested one of the main carotenoids of the diatom, the xanthophyll pigment fucoxanthin (Fuco). Fuco from the literature is a potential candidate compound involved in chemopreventive activities. Sm extract and Fuco were able to inhibit PCa cell growth and hinder vascular network formation of endothelial cells. The reduced number of cells was partially due to growth inhibition and apoptosis. We studied the molecular targets by qPCR and membrane antibody arrays. Angiogenesis and inflammation molecules were modulated. In particular, Fuco downregulated the expression of Angiopoietin 2, CXCL5, TGFß, IL6, STAT3, MMP1, TIMP1 and TIMP2 in both prostate and endothelial cells. Our study confirmed microalgae-derived drugs as potentially relevant sources of novel nutraceuticals, providing candidates for potential dietary or dietary supplement intervention in cancer prevention approaches.

Dietary Protective Potential of Fucoxanthin as an Active Food Component on Neurological Disorders.

The prevalence of neurodegenerative, cerebrovascular, and psychiatric diseases and other neurological disorders has increased dramatically worldwide. Fucoxanthin is an algal pigment with many biological functions, and there is rising evidence that fucoxanthin plays a preventive and therapeutic role in neurological disorders. This review focuses on the metabolism, bioavailability, and blood-brain barrier penetration of fucoxanthin. Furthermore, the neuroprotective potential of fucoxanthin in neurodegenerative diseases, cerebrovascular diseases, and psychiatric diseases as well as other neurological disorders such as epilepsy, neuropathic pain, and brain tumors by acting on multiple targets will be summarized. The multiple targets include regulating apoptosis, reducing oxidative stress, activating the autophagy pathway, inhibiting Aß aggregation, improving dopamine secretion, reducing α-synuclein aggregation, attenuating neuroinflammation, modulating gut microbiota, and activating brain-derived neurotrophic factor, etc. Additionally, we look forward to brain-targeted oral transport systems due to the low bioavailability and blood-brain barrier permeability of fucoxanthin. We also propose exploring the systemic mechanisms of fucoxanthin metabolism and transport through the gut-brain process and envision new therapeutic targets for fucoxanthin to act on the central nervous system. Finally, we propose dietary fucoxanthin delivery interventions to achieve preventive effects on neurological disorders. This review provides a reference for the application of fucoxanthin in the neural field.

Dietary astaxanthin: an excellent carotenoid with multiple health benefits.

Astaxanthin is a carotenoid widely found in marine organisms and microorganisms. With extensive use in nutraceuticals, cosmetics, and animal feed, astaxanthin will have the largest share in the global market for carotenoids in the near future. Owing to its unique molecular features, astaxanthin has excellent antioxidant activity and holds promise for use in biochemical studies. This review focuses on the observed health benefits of dietary astaxanthin, as well as its underlying bioactivity mechanisms. Recent studies have increased our understanding of the role of isomerization and esterification in the structure-function relationship of dietary astaxanthin. Gut microbiota may involve the fate of astaxanthin during digestion and absorption; thus, further knowledge is needed to establish accurate recommendations for dietary intake of both healthy and special populations. Associated with the regulation of redox balance and multiple biological mechanisms, astaxanthin is proposed to affect oxidative stress, inflammation, cell death, and lipid metabolism in humans, thus exerting benefits for skin condition, eye health, cardiovascular system, neurological function, exercise performance, and immune response. Additionally, preclinical trials predict its potential effects such as intestinal flora regulation and anti-diabetic activity. Therefore, astaxanthin is worthy of further investigation for boosting human health, and wide applications in the food industry.

The Role of Astaxanthin as a Nutraceutical in Health and Age-Related Conditions.

The current review provides an up-to-date analysis of scientific data on astaxanthin (ASX) sources and experimental studies on its health benefits as a potent antioxidant in the aging process. ASX is a liposoluble carotenoid nutrient and reddish-orange pigment, naturally synthesized by numerous microalgae, yeasts, and bacteria as secondary metabolites. Provides a reddish hue to redfish and shellfish flesh that feed on ASX-producing microorganisms. The microalga Haematococcus pluvialis is the most important source for its industrial bioproduction. Due to its strong antioxidant properties, numerous investigations reported that natural ASX is a more significant antioxidant agent than other antioxidants, such as vitamin C, vitamin E, and ß-carotene. Furthermore, several data show that ASX possesses important nutraceutical applications and health benefits, especially in healthy aging processes. However, further studies are needed for a deeper understanding of the potential mechanisms through which ASX could lead to its effective role in the healthy aging process, such as supporting brain health and skin homeostasis. This review highlights the current investigations on the effective role of ASX in oxidative stress, aging mechanisms, skin physiology, and central nervous system functioning, and shows the potential clinical implications related to its consumption.

Study on the Interaction between Four Typical Carotenoids and Human Gut Microflora Using an in Vitro Fermentation Model.

Recent studies indicated a strong relationship between carotenoids and gut microflora. However, their structure-activity relationship remains unclear. This study evaluated the interaction between four typical carotenoids (ß-carotene, lutein, lycopene, and astaxanthin) and gut microflora using an in vitro fermentation model. After 24 h of fermentation, the retention rates of the four carotenoids were 1.40, 1.38, 1.46, and 5.63 times lower than those of their without gut microflora control groups, respectively. All four carotenoid treated groups significantly increased total short-chain fatty acids (SCFAs) production. All carotenoid supplements significantly promoted the abundance of Roseburia and Parasutterella and inhibited the abundance of Collinsella, while ß-carotene, lutein, lycopene, and astaxanthin significantly promoted the abundance of Ruminococcus, Sutterella, Subdoligranulum, and Megamonas, respectively. Furthermore, xanthophylls have a more significant impact on gut microflora than carotenes. This study provides a new way to understand how carotenoids work in the human body with the existing gut microflora.

The effects of astaxanthin supplementation on expression of microRNAs involved in cardiovascular diseases: a systematic review of current evidence.

MicroRNAs (miRNAs) have biological roles in controlling oxidative stress. Astaxanthin (AST) may regulate circulating miRNAs in cardiovascular diseases (CVDs); therefore, our study aimed to evaluate the effect of AST on miRNA involved in CVDs. A systematic literature search from inception to August 2022 resulted in 80 preliminary studies; 15 articles were included. In vitro studies indicated that AST up-regulated miRNAs compromised miR-138, miR-7, miR-29a-3p, and miR-200a, while down-regulated miR-382-5p, miR-31-5p, and miR-21. In vivo articles revealed that AST increased the expression of miR-124, miR-7, miR-29a-3p, and miR-200a but decreased miR-21 and miR-31-5p and the only clinical study showed a drop in miR-146a. The findings indicate that AST regulated different pathways of miRNAs implicated in various conditions. Therefore AST as a new therapeutic strategy could be essential in preventing and controlling CVDs. However, more studies, including clinical trials, are needed to determine the influence of AST on miRNAs associated with CVDs.

Oral Supplementation with Z-Isomer-Rich Astaxanthin Inhibits Ultraviolet Light-Induced Skin Damage in Guinea Pigs.

The effect of oral supplementation with astaxanthin of different Z-isomer ratios on ultraviolet (UV) light-induced skin damage in guinea pigs was investigated. Astaxanthin with a high Z-isomer content was prepared from the all-E-isomer via thermal isomerization. Intact (all-E)-astaxanthin and the prepared Z-isomer-rich astaxanthin were suspended in soybean oil and fed to guinea pigs for three weeks. The UV-light irradiation was applied to the dorsal skin on the seventh day after the start of the test diet supplementation, and skin parameters, such as elasticity, transepidermal water loss (TEWL), and pigmentation (melanin and erythema values), were evaluated. The accumulation of astaxanthin in the dorsal skin was almost the same after consumption of the all-E-isomer-rich astaxanthin diet (E-AST-D; total Z-isomer ratio = 3.2%) and the Z-isomer-rich astaxanthin diet (Z-AST-D; total Z-isomer ratio = 84.4%); however, the total Z-isomer ratio of astaxanthin in the skin was higher in the case of the Z-AST-D supplementation. Both diets inhibited UV light-induced skin-damaging effects, such as the reduction in elasticity and the increase in TEWL level. Between E-AST-D and Z-AST-D, Z-AST-D showed better skin-protective ability against UV-light exposure than E-AST-D, which might be because of the greater UV-light-shielding ability of astaxanthin Z-isomers than the all-E-isomer. Furthermore, supplementation with Z-AST-D resulted in a greater reduction in skin pigmentation caused by astaxanthin accumulation compared to that of E-AST-D. This study indicates that dietary astaxanthin accumulates in the skin and appears to prevent UV light-induced skin damage, and the Z-isomers are more potent oral sunscreen agents than the all-E-isomer.

New Insights into Xanthophylls and Lipidomic Profile Changes Induced by Glucose Supplementation in the Marine Diatom Nitzschia laevis.

Nitzschia laevis is a candidate microorganism for bioactive compounds (fucoxanthin and eicosapentaenoic acid (EPA)) production. In this study, the impacts of glucose-induced trophic transition on biomass, photosynthesis, pigments, and lipid profiles were examined. The specific growth rate was increased under glucose addition, achieved at 0.47 day-1 (0.26 ± 0.01 day-1 for the group without glucose in medium). However, the photosynthetic parameters and pigments including chlorophylls, fucoxanthin, and diatoxanthin were reduced. The net yield of EPA doubled under glucose addition, reaching 20.36 ± 1.22 mg/L in 4 days. In addition, the alteration in detailed lipid molecular species was demonstrated with a focus on EPA-enriched lipids. The effects of 2-deoxyglucose (2DG) indicated that glucose phosphorylation was involved in glucose-induced regulation. These findings provide novel data for guiding the application of this diatom strain in the functional food industries.

Consumption of Low Dose Fucoxanthin Does Not Prevent Hepatic and Adipose Inflammation and Fibrosis in Mouse Models of Diet-Induced Obesity.

Fucoxanthin (FCX) is a xanthophyll carotenoid present in brown seaweed. The goal of this study was to examine whether FCX supplementation could attenuate obesity-associated metabolic abnormalities, fibrosis, and inflammation in two diet-induced obesity (DIO) mouse models. C57BL/6J mice were fed either a high-fat/high-sucrose/high-cholesterol (HFC) diet or a high-fat/high-sucrose (HFS) diet. The former induces more severe liver injury than the latter model. In the first study, male C57BL/6J mice were fed an HFC diet, or an HFC diet containing 0.015% or 0.03% (w/w) FCX powder for 12 weeks to develop obesity-induced nonalcoholic steatohepatitis (NASH). In the second study, mice were fed an HFS diet or an HFS diet containing 0.01% FCX powder for 8 weeks. FCX did not change body weight gain and serum lipid profiles compared to the HFC or HFS controls. No significant differences were present in liver triglyceride and total cholesterol, hepatic fat accumulation, and serum alanine aminotransferase levels between control and FCX-fed mice regardless of whether they were on an HFC or HFS diet. FCX did not mitigate mRNA abundance of genes involved in lipid synthesis, cholesterol metabolism, inflammation, and fibrosis in the liver and white adipose tissue, while hepatic fatty acid ß-oxidation genes were significantly elevated by FCX in both HFC and HFS feeding studies. Additionally, in the soleus muscle, FCX supplementation significantly elevated genes that regulate mitochondrial biogenesis and fatty acid ß-oxidation, concomitantly increasing mitochondrial DNA copy number, compared with HFC. In summary, FCX supplementation had minor effects on hepatic and white adipose inflammation and fibrosis in two different DIO mouse models.

Fucoxanthin Attenuates Free Fatty Acid-Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism/Oxidative Stress/Inflammation via the AMPK/Nrf2/TLR4 Signaling Pathway.

Fucoxanthin, a xanthophyll carotenoid abundant in brown algae, is reported to have several biological functions, such as antioxidant, anti-inflammatory, and anti-tumor activities, in mice. We investigated the effects and mechanisms of fucoxanthin in the mixture oleate/palmitate = 2/1(FFA)-induced nonalcoholic fatty liver disease (NAFLD) cell model in this study. The results showed that the content of superoxide dismutase in the FFA group was 9.8 ± 1.0 U/mgprot, while that in the fucoxanthin high-dose (H-Fx) group (2 µg/mL) increased to 22.9 ± 0.6 U/mgprot. The content of interleukin-1ß in the FFA group was 89.3 ± 3.6 ng/mL, while that in the H-Fx group was reduced to 53.8 ± 2.8 ng/mL. The above results indicate that fucoxanthin could alleviate the FFA-induced oxidative stress and inflammatory levels in the liver cells. Oil red-O staining revealed visible protrusions and a significant decrease in the number of lipid droplets in the cytoplasm of cells in the fucoxanthin group. These findings on the mechanisms of action suggest that fucoxanthin can repair FFA-induced NAFLD via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and nuclear factor erythroid-2-related factor 2-mediated (Nrf2) signaling pathway, as well as by downregulating the expression of the Toll-like receptor 4-mediated (TLR4) signaling pathway. Fucoxanthin exhibited alleviating effects in the FFA-induced NAFLD model and could be explored as a potential anti-NAFLD substance.

Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells.

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson's disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 µM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.