fucoxanthin and Disease-Models--Animal

Obesity, which results from an imbalance between energy intake and energy expenditure, has become a major health risk factor worldwide, causing numerous and various diseases such as diabetes, hypertension, and cardiovascular diseases. Fucoxanthin, a specific carotenoid in brown algae, has garnered much attention for its anti-obesity and anti-diabetic effects attributable to a unique mechanism. Fucoxanthin induces uncoupling protein 1 (UCP1) expression in white adipose tissue (WAT). That inner membrane mitochondrial protein, UCP1, can dissipate energy through oxidation of fatty acids and heat production. Furthermore, fucoxanthin improves insulin resistance and ameliorates blood glucose levels through down-regulation of adipocytokines related to insulin resistance in WAT and up-regulation of glucose transporter 4 (GLUT4) in skeletal muscle. Algae fucoxanthin is a beneficial compound for the prevention of the metabolic syndrome.

Topics: Adipokines; Adipose Tissue, White; Animals; Blood Glucose; Diabetes Mellitus; Disease Models, Animal; Energy Metabolism; Fatty Acids; Gene Expression; Gene Expression Regulation, Plant; Glucose Transporter Type 4; Humans; Insulin Resistance; Ion Channels; Metabolic Syndrome; Mice; Mitochondrial Proteins; Muscle, Skeletal; Obesity; Oxidation-Reduction; Phaeophyceae; Phytotherapy; Uncoupling Protein 1; Xanthophylls

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRG

Topics: Adiponectin; Adult; Aged; Animals; Cell Line; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Middle Aged; Non-alcoholic Fatty Liver Disease; Polysaccharides; Xanthophylls; Young Adult

Fucoxanthin (Fx), a dietary marine xanthophyll, exerts potent anticancer effects in various colorectal cancer (CRC) animal models. However, therapeutic effects of Fx in human cancer tissues remain unclear. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissues from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates.. Herein, we investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with CRC (CRC-PDX) using LC-MS/MS- and western blot-based proteome analysis.. Fx suppresses development of human-like CRC tissues, especially through growth, adhesion, and cell cycle signals.

Topics: Animals; Cell Cycle; Chromatography, Liquid; Chromosomal Proteins, Non-Histone; Colorectal Neoplasms; Disease Models, Animal; Humans; Mice; Tandem Mass Spectrometry; Xanthophylls

Topics: Animals; Azoxymethane; Chemokines, CC; Colonic Neoplasms; Cyclin D1; Dextran Sulfate; Disease Models, Animal; Humans; Male; Mice; Mice, Inbred ICR; Proto-Oncogene Proteins c-akt; Receptors, CCR1; Smad2 Protein; Xanthophylls

Topics: Animals; Antioxidants; Apoptosis; Cell Hypoxia; Cell Line; Disease Models, Animal; Epithelial Cells; Heme Oxygenase-1; Humans; Kidney Diseases; Kidney Tubules, Proximal; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Sirtuin 1; Transfection; Treatment Outcome; Xanthophylls

Topics: Animals; Azoxymethane; Carcinogenesis; Colitis; Colorectal Neoplasms; Dextran Sulfate; Disease Models, Animal; Humans; Mice; Xanthophylls

This study aimed to determine whether fucoxanthin alleviated ovalbumin (OVA)-induced food allergy (FA) and explored the possible mechanisms. The results indicated that supplementation with fucoxanthin at 10.0-20.0 mg/kg per day for 7 weeks inhibited food anaphylaxis and the production of immunoglobulin (Ig) E, IgG, histamine, and related cytokines while alleviating allergic symptoms in sensitized mice. Fucoxanthin enhanced the intestinal epithelial barrier by up-regulating tight junction (TJ) protein expression and promoting regenerating islet-derived protein III-gamma (RegIIIγ) and secretory IgA (sIgA) secretion. In addition, fucoxanthin induced the secretion of anti-inflammatory factors (interleukin (IL)-10 and transforming growth factor β (TGF-β)) by regulatory T (Treg) cells and decreased the pro-inflammatory factor levels (IL-4, tumor necrosis factor-α (TNF-α), IL-17, and IL-1β), ameliorating intestinal inflammation. Compared with the model group, beneficial bacteria, such as Lactobacillaceae, increased in the intestinal flora, while pathogenic bacteria like Helicobacteraceae, Desulfovibrionaceae, and Streptococcaceae decreased. Therefore, fucoxanthin may effectively prevent FA by enhancing the intestinal epithelial barrier and reshaping the intestinal flora.

Topics: Animals; Cytokines; Disease Models, Animal; Food Hypersensitivity; Gastrointestinal Microbiome; Immunoglobulin E; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Ovalbumin; Xanthophylls

Alzheimer's disease (AD) is a neurological disorder characterized by loss of memory and cognitive functions caused by oxidative stress, neuroinflammation, change in neurotransmitter levels, and excessive deposition of Aβ. In the present study, fucoxanthin was employed as a protective strategy in Intracerebroventricular Streptozotocin (ICV-STZ) induced experimental model of cognitive impairment.. STZ was injected twice ICV (3 mg/kg) on alternate days 1 and 3, and Wistar rats were evaluated for the memory analysis using Morris water maze and elevated plus-maze. Fucoxanthin at low 50 mg/kg, p.o. and high dose 100 mg/kg, p.o. was administered for 14 days. All animals were sacrificed on day 29, and brain hippocampus tissue after isolation was used for biochemical (MDA, nitrite, GSH, SOD and Catalase), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (ACh, GABA Glutamate), Aβ. STZ-infused rats showed significant impairment in learning and memory, increased oxidative stress (MDA, nitrite), reduced antioxidant defense (GSH, SOD and Catalase), promoted cytokine release, and change in neurotransmitters level. However, fucoxanthin improved cognitive functions, restored antioxidant levels, reduced inflammatory markers dose-dependently, and restored neurotransmitters concentration.. The finding of the current study suggests that fucoxanthin could be the promising compound for improving cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms, and inhibition of acetylcholinesterase (AChE) enzyme activities, Aβ

Topics: Acetylcholinesterase; Animals; Cognitive Dysfunction; Disease Models, Animal; Maze Learning; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Streptozocin; Xanthophylls

Fucoxanthin (Fx), a marine carotenoid found in edible brown algae, is well known for having anticancer properties. The gut microbiota has been demonstrated as a hallmark for colorectal cancer progression in both humans and rodents. However, it remains unclear whether the gut microbiota is associated with the anticancer effect of Fx. We investigated the chemopreventive potency of Fx and its effect on gut microbiota in a mouse model of inflammation-associated colorectal cancer (by azoxymethane/dextran sulfate sodium treatment). Fx administration (30 mg/kg bw) during a 14 week period significantly inhibited the multiplicity of colorectal adenocarcinoma in mice. The number of apoptosis-like cleaved caspase-3high cells increased significantly in both colonic adenocarcinoma and mucosal crypts. Fx administration significantly suppressed Bacteroidlales (f_uc; g_uc) (0.3-fold) and Rikenellaceae (g_uc) (0.6-fold) and increased Lachnospiraceae (g_uc) (2.2-fold), compared with those of control mice. Oral administration of a fecal suspension obtained from Fx-treated mice, aimed to enhance Lachnospiraceae, suppress the number of colorectal adenocarcinomas in azoxymethane/dextran sulfate sodium-treated mice with a successful increase in Lachnospiraceae in the gut. Our findings suggested that an alteration in gut microbiota by dietary Fx might be an essential factor in the cancer chemopreventive effect of Fx in azoxymethane/dextran sulfate sodium-treated mice.

Topics: Adenocarcinoma; Animals; Azoxymethane; Colitis-Associated Neoplasms; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Drug Screening Assays, Antitumor; Feces; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Male; Mice; Xanthophylls

Chronic kidney disease (CKD) is a common global progressive disease, but there are no ideal drugs for the treatment. Fucoidan and fucoxanthin, and L-carnitine are one of the very few natural products that have a therapeutic effect on CKD in animal experiments. However, the combined effects of these compounds on CKD are unknown. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Oligo-fucoidan and fucoidan were extracted from Laminaria japonica. We fed CKD mice with the two compounds and L-carnitine to evaluate the combined effects on CKD. Oligo-fucoidan and fucoidan inhibited renal fibrosis and reduced serum creatine in CKD mice to a greater extent than any single compound. L-carnitine had no measurable effect on renal fibrosis but promoted the protective effect of the mixture of oligo-fucoidan and fucoidan on renal function in CKD mice. In the two-month safety test, the combined mixture further improved renal function and did not elevate serum aspartate aminotransferase and alanine aminotransferase levels in CKD mice. Furthermore, the weights of CKD mice treated with the combination increased to the normal level. We also found that all oligo-fucoidan, fucoxanthin, and L-carnitine inhibit H

Topics: Animals; Apoptosis; Biomarkers; Carnitine; Cell Line; Disease Models, Animal; Drug Therapy, Combination; Enzyme Activation; Fibrosis; Kidney; Mice, 129 Strain; Oxidative Stress; Polysaccharides; Proto-Oncogene Proteins c-akt; Rats; Renal Insufficiency, Chronic; Xanthophylls

Oxidative stress is identified as a major inducer of retinal pigment epithelium (RPE) cell dysregulation and is associated with age-related macular degeneration (AMD). The protection of RPE disorders plays an essential role in the pathological progress of retinal degeneration diseases. The pharmacological functions of fucoxanthin, a characteristic carotenoid, including anti-inflammatory and antioxidant properties, may ameliorate an outstanding bioactivity against premature senescence and cellular dysfunction. This study demonstrates that fucoxanthin protects RPE cells from oxidative stress-induced premature senescence and decreased photoreceptor cell loss in a sodium iodate-induced AMD animal model. Similarly, oxidative stress induced by hydrogen peroxide, nuclear phosphorylated histone (γH2AX) deposition and premature senescence-associated β-galactosidase staining were inhibited by fucoxanthin pretreatment in a human RPE cell line, ARPE-19 cells. Results reveal that fucoxanthin treatment significantly inhibited reactive oxygen species (ROS) generation, reduced malondialdehyde (MDA) concentrations and increased the mitochondrial metabolic rate in oxidative stress-induced RPE cell damage. Moreover, atrophy of apical microvilli was inhibited in cells treated with fucoxanthin after oxidative stress. During aging, the RPE undergoes well-characterized pathological changes, including amyloid beta (Aβ) deposition, beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) expression and tight junction disruption, which were also reduced in fucoxanthin-treated groups by immunofluorescence. Altogether, pretreatment with fucoxanthin may protect against premature senescence and cellular dysfunction in retinal cells by oxidative stress in experimental AMD animal and human RPE cell models.

Topics: Animals; Antioxidants; Cell Line; Cellular Senescence; Disease Models, Animal; Humans; Macular Degeneration; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Retinal Pigment Epithelium; Xanthophylls

A xanthophyll of fucoxanthin (Fx) is a potential chemopreventive agent. Familial adenomatous polyposis (FAP) is an inherited disease that is associated with a high risk of developing colorectal cancer. However, it remains unclear whether Fx can modify colorectal tumorigenesis in Apc. We investigated the chemopreventive effect of Fx in dextran sodium sulfate (DSS)-treated Apc. Administration of Fx in the diet for 5 weeks significantly suppressed the number of colorectal adenocarcinomas in DSS-treated male Apc. Fx possesses chemopreventive potential against progression of colorectal carcinogenesis in Apc

Topics: Adenomatous Polyposis Coli; Animals; Anticarcinogenic Agents; Colorectal Neoplasms; Cyclin D1; Dextran Sulfate; Disease Models, Animal; Male; Mice; Xanthophylls

Myoinositol (M) and D-chiro-inositol (D) are insulin sensitizer compounds, while fucoxanthin (F) and hydroxytyrosol (H) are antioxidant substances. We aim to investigate if the combination of these compounds, will improve the vascular responses in pregnant mouse models of hypertension: a genetic model, transgenic heterozygous mice lacking endothelial nitric oxide synthase gene (eNOS-/+); and environmental, wild-type (WT) mice. Those mouse models will allow a better understanding of the genetic/environmental contribution to hypertension in pregnancy.. eNOS-/+ and WT female were fed high fat diet for 4 weeks, then at 7-8 weeks of age were mated with WT male. On gestational day (GD) 1, they were randomly allocated to receive MDFH treatment or water as control: eNOS-/+ MDFH (n = 13), eNOS-/+ (n = 13), WT-MDFH (n = 14), and WT (n = 20). Systolic blood pressure (SBP) was obtained at GD 18, then dams were sacrificed; fetuses and placentas collected, and 2 mm segments of carotid arteries isolated for vascular responses using the wire-myograph system. Responses to phenylephrine (PE), with/without the NOS inhibitor (N-nitro-l-arginine methyl ester (l-NAME)), and to acetylcholine (Ach) and sodium nitroprussiate (SNP) were performed.. SBP decreased in eNOS-/+ and WT dams after MDFH supplementation. In eNOS-/+, MDFH lower the contractile response to PE and l-NAME and improved Ach vasorelaxation. In WT dams, MDFH treatment did not affect PE response; MDFH treatment lowered the vascular PE response after incubation with l-NAME. No differences were seen in SNP relaxation in both models.. MDFH decreased SBP in both genetically and environmentally hypertensive dams and improved vascular responses mostly in the eNOS-/+ dams.

Topics: Animals; Antioxidants; Dietary Supplements; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Hypertension; Inositol; Mice; Mice, Knockout; Phenylethyl Alcohol; Pregnancy; Random Allocation; Xanthophylls

Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte injury, excessive oxidative stress, and chronic inflammation in fatty liver, and can progress to more severe liver diseases, such as cirrhosis and hepatocellular carcinoma. However, currently there are no effective therapies for NASH. Marine carotenoid, fucoxanthin (Fx), abundant in brown seaweeds, has variable biological properties, such as anti-cancer, anti-inflammatory, anti-oxidative and anti-obesity. However, the effect of Fx on the development of NASH has not been explored. We investigated the protective effects of Fx in diet-induced NASH model mice fed choline-deficient L-amino acid-defined high fat diet (CDAHFD). Fx administration significantly attenuated liver weight gain and hepatic fat accumulation, resulting in the alleviation of hepatic injury. Furthermore, the Fx-fed mice, not only exhibited reduced hepatic lipid oxidation, but also decreased mRNA expression levels of inflammation and infiltration-related genes compared to that of the CDAHFD-fed mice. Moreover, fucoxanthinol and amarouciaxanthin A, two Fx metabolites exerted anti-inflammatory effects in the liver via inhibiting the chemokine production in hepatocytes. In case of fibrosis, one of the features of advanced NASH, the expression of fibrogenic factors including activated-hepatic stellate cell marker was significantly decreased in the liver of Fx-fed mice. Thus, the present study elucidated that dietary Fx not only inhibited hepatic oxidative stress and inflammation but also prevented early phase of fibrosis in the diet-induced NASH model mice.

Topics: Alanine Transaminase; Amino Acids; Animals; Anti-Inflammatory Agents; Aspartate Aminotransferases; Biomarkers; Cell Line; Choline; Diet, High-Fat; Disease Models, Animal; Gene Expression Regulation; Hepatic Stellate Cells; Inflammation; Lipid Metabolism; Liver; Liver Cirrhosis; Male; Metabolome; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; RNA, Messenger; Xanthophylls

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.

Topics: Animals; Antioxidants; Blood Glucose; Cell Survival; Diabetes Mellitus, Experimental; Disease Models, Animal; Inflammation Mediators; Insulin; Insulin Resistance; Kisspeptins; Male; Malondialdehyde; Mice; Niacinamide; Nitric Oxide; Oxidative Stress; Phaeophyceae; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive Oxygen Species; Receptors, Kisspeptin-1; Reproduction; RNA, Messenger; Spermatozoa; Streptozocin; Suppressor of Cytokine Signaling 3 Protein; Testis; Xanthophylls

Fucoxanthin (Fx) is a natural extract from marine seaweed that has strong antioxidant activity and a variety of other bioactive effects. This study elucidated the protective mechanism of Fx on alcoholic liver injury. Administration of Fx was associated with lower pathological effects in liver tissue and lower serum marker concentrations for liver damage induced by alcohol. Fx also alleviated oxidative stress, and lowered the level of oxides and inflammation in liver tissue. Results indicate that Fx attenuated alcohol-induced oxidative lesions and inflammatory responses by activating the nuclear factor erythrocyte-2-related factor 2 (Nrf2)-mediated signaling pathway and down-regulating the expression of the toll-like receptor 4 (TLR4)-mediated nuclear factor-kappa B (NF-κB) signaling pathway, respectively. Our findings suggest that Fx can be developed as a potential nutraceutical for preventing alcohol-induced liver injury in the future.

Topics: Animals; Dietary Supplements; Disease Models, Animal; Ethanol; Humans; Inflammation; Liver; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred ICR; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Seaweed; Signal Transduction; Toll-Like Receptor 4; Xanthophylls

Allergic rhinitis is a sensitivity to allergens that causes swelling or puffiness of the nasal airways. The occurrence of allergic rhinitis is mounting worldwide. We examined whether fucoxanthin restrains the development of allergic rhinitis provoked by ovalbumin (OVA). In this study, allergic rhinitis in male BALB/c mice was induced with OVA. The object was to evaluate the effect of fucoxanthin on consequently allergic mice. Allergic responses like rubbing and sneezing were scored to reveal the effect of fucoxanthin in the induced and treated groups. Mean histological scores demonstrated variation in and between OVA-induced and fucoxanthin-treated groups in terms of ciliary loss, eosinophil infiltration, and the like. Lipid profiling (malondialdehyde) confirmed the restraining effect of fucoxanthin on allergic rhinitis. The present study showed that cytokine production, the induction of cell survival molecule NF-κB p65, and subsequent prevention of IκBα phosphorylation are controlled by fucoxanthin, and that interleukins (IL-5, IL-6, and IL-12) support STAT-3 binding to key elements that control IL-17A expression. Additionally, the study showed that interleukin-induced NF-κB and IκBα directly regulate interleukins in collaboration with STAT-3 and related cytokines. Levels of IgE and histamine are the most frequent medications used to treat allergic rhinitis. Considering our findings, we concluded that fucoxanthin represses the development of allergic rhinitis induced by OVA and thus might be a positive drug for its management.

Topics: Animals; Cytokines; Disease Models, Animal; Interleukin-17; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Protective Agents; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor; Transcription Factor RelA; Xanthophylls

Fucoxanthin is a carotenoid with many pharmaceutical properties that is found in brown seaweed. However, the effects of fucoxanthin on corneal innervation and intense eye pain have not been extensively examined. To clarify the protective roles and underlying mechanisms of fucoxanthin on ocular lesions, we investigated the beneficial effects and mechanisms by which fucoxanthin ameliorates ultraviolet B (UVB)-induced corneal denervation and trigeminal pain. Treatment with fucoxanthin enhanced the expression of nuclear factor erythroid 2-related factor 2 in the cornea. Inhibition of typical denervation and epithelial exfoliation in the cornea were observed in rats treated with fucoxanthin following UVB-induced nerve disorders. Moreover, the active phosphorylated form of p38 MAP kinase (pp38) and the number of glial fibrillary acidic protein (GFAP)-positive neural cells were significantly reduced. Decreased expression of neuron-selective transient receptor potential vanilloid type 1 (TRPV1) in the trigeminal ganglia neurons was also demonstrated in rats treated with fucoxanthin after UVB-induced keratitis. Symptoms of inflammatory pain, including difficulty in opening the eyes and eye wipe behaviour, were also reduced in fucoxanthin-treated groups. Pre-treatment with fucoxanthin may protect the eyes from denervation and inhibit trigeminal pain in UVB-induced photokeratitis models.

Topics: Administration, Oral; Animals; Cornea; Denervation; Disease Models, Animal; Eye Pain; Humans; Keratitis; Male; Neurons; Protective Agents; Rats; Rats, Sprague-Dawley; Seaweed; Trigeminal Ganglion; TRPV Cation Channels; Ultraviolet Rays; Xanthophylls

In the present study, an attempt was made to determine whether administration of fucoxanthin could attenuate cerebral ischemic/reperfusion (I/R) injury and its possible mechanisms using an in vivo middle cerebral artery occlusion (MCAO) model and an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model. Fucoxanthin was intragastrically administrated in different doses (30 mg/kg, 60 mg/kg, and 90 mg/kg, respectively) to the rats 1 h before MCAO induction. The neurological function, infarct area and brain water content of rats were then evaluated. Rat cortical neuron were pretreated with different doses of fucoxanthin (5 μM, 10 μM, and 20 μM) and then subjected to OGD/R. Expression levels of proteins in the brain tissues and cultured cells were determined by western blotting. Our results demonstrated that fucoxanthin pretreatment improved the neurologic deficit score, lowered the infarct volume and reduced the expression of apoptosis-associated proteins in brain tissues. In addition, fucoxanthin also suppresses OGD/R-induced apoptosis and ROS accumulation in cultured neurons. Furthermore, we found that fucoxanthin could significantly activate the Nrf2/HO-1 signaling through inducing Nrf2 nuclear translocation with enhanced HO-1 expression, and Nrf2 knockdown obviously abrogated the beneficial role of fucoxanthin in OGD/R-treated neurons. These findings suggested that fucoxanthin could be exploited as a therapeutic target for protecting neurons from cerebral I/R injury.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Brain; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Heme Oxygenase (Decyclizing); Infarction, Middle Cerebral Artery; Male; Neurons; Neuroprotective Agents; NF-E2-Related Factor 2; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Superoxide Dismutase; Xanthophylls

The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose; Homeostasis; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Interleukin-6; Lipid Metabolism; Liver; Mice; Molecular Weight; Polysaccharides; PPAR gamma; Tumor Necrosis Factor-alpha; Xanthophylls

Undaria pinnatifida is a well-known traditional Korean food with a variety of biological activities. Carrageenan (carr) is commonly used to induce paw edema in animal models. This study was designed to elucidate the processes underlying the anti-inflammatory effect of fucoxanthin isolated from the sporophyll of U. pinnatifida in carr-induced paw edema in ICR mice. Fucoxanthin significantly decreased carr-induced increased nitric oxide levels in the plasma of mice with carr-induced paw edema. Fucoxanthin protected catalase (CAT) and superoxide dismutase (SOD) activity against disruption in mice with carr-induced paw edema. In addition, fucoxanthin repressed carr-induced activation of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa B, as well as carr-induced phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and protein kinase B/Akt. These results suggest that fucoxanthin may have therapeutic potential as a treatment for patients with inflammatory diseases.

Topics: Animals; Catalase; Cyclooxygenase 2; Disease Models, Animal; Edema; Inflammation; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Proto-Oncogene Proteins c-akt; Superoxide Dismutase; Xanthophylls

Ultraviolet B (UVB) irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues against oxidative UVB-induced corneal injury. The experimental rats were intravenously injected with fucoxanthin at doses of 0.5, 5 mg/kg body weight/day or with a vehicle before UVB irradiation. Lissamine green for corneal surface staining showed that UVB irradiation caused serious damage on the corneal surface, including severe epithelial exfoliation and deteriorated epithelial smoothness. Histopathological lesion examination revealed that levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF), significantly increased. However, pretreatment with fucoxanthin inhibited UVB radiation-induced corneal disorders including evident preservation of corneal surface smoothness, downregulation of proinflammatory cytokine expression, and decrease of infiltrated polymorphonuclear leukocytes from UVB-induced damage. Moreover, significant preservation of the epithelial integrity and inhibition of stromal swelling were also observed after UVB irradiation in fucoxanthin-treated groups. Pretreatment with fucoxanthin may protect against UVB radiation-induced corneal disorders by inhibiting expression of proinflammatory factors, TNF-α, and VEGF and by blocking polymorphonuclear leukocyte infiltration.

Topics: Animals; Antioxidants; Cornea; Corneal Diseases; Disease Models, Animal; Male; Rats; Rats, Sprague-Dawley; Seawater; Seaweed; Tumor Necrosis Factor-alpha; Ultraviolet Rays; Vascular Endothelial Growth Factor A; Xanthophylls

Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related.

Topics: Acetyl-CoA Carboxylase; Adiponectin; Adipose Tissue, White; Animals; Biomarkers; Diet, High-Fat; Diet, Vegetarian; Disease Models, Animal; Humans; Inflammation; Interleukin-6; Lipogenesis; Male; Metabolic Syndrome; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phaeophyceae; PPAR alpha; PPAR gamma; Rats; Rats, Wistar; Uncoupling Protein 1; Undaria; Xanthophylls

Fucoxanthin (Fx) is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary Fx metabolite into fucoxanthinol (FxOH), attenuates the weight gain of white adipose tissue of diabetic/obese KK-Ay mice. In this study, to evaluate anti-diabetic effects of Fx, we investigated improving the effect of insulin resistance on the diabetic model of KK-Ay mice. Furthermore, preventing the effect of FxOH on low-grade chronic inflammation related to oxidative stress was evaluated on 3T3-L1 adipocyte cells and a RAW264.7 macrophage cell co-culture system. A diet containing 0.1% Fx was fed to diabetic model KK-Ay mice for three weeks, then glucose tolerance was observed. Fx diet significantly improved glucose tolerance compared with the control diet group.  In in vitro studies, FxOH showed suppressed tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1) mRNA expression and protein levels in a co-culture of adipocyte and macrophage cells. These findings suggest that Fx ameliorates glucose tolerance in the diabetic model mice. Furthermore, FxOH, a metabolite of Fx, suppresses low-grade chronic inflammation in adipocyte cells.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue, White; Animals; beta Carotene; Blood Glucose; Cell Line; Chemokine CCL2; Diabetes Mellitus, Experimental; Diet; Disease Models, Animal; Inflammation; Insulin Resistance; Macrophages; Mice; Obesity; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain; Xanthophylls

Obesity, characterized as a state of low-level inflammation, is a powerful determinant influencing the development of insulin resistance and progression to type 2 diabetes. The purpose of the present study was to investigate the anti-inflammatory activity of fucoxanthin in experimental high-fat-diet-induced obesity in mice and antioxidant activity in PC12 cells under oxidative stress situation. The anti-inflammatory potential of fucoxanthin in the regulation of maleic dialdehyde (MDA), polymorphonuclear cells (PMNs), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and cyclooxygenase-2 (COX-2) was determined by ELISA. Fucoxanthin significantly inhibited obesity-induced upregulation of the production of IL-1β, TNF-α, iNOS, and COX-2. Moreover, fucoxanthin suppressed MDA and infiltration of PMNs. The protective effects were associated with lack of hypertrophy and crown-like structures in mammary gland. At the same time, fucoxanthin showed an advantage of antioxidant activity in PC12 cells under oxidative stress situation. These results suggest that supplementation of fucoxanthin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Antioxidants; Cyclooxygenase 2; Dietary Fats; Disease Models, Animal; Inflammation; Inflammation Mediators; Interleukin-1beta; Macrophages; Malondialdehyde; Mice; Nitric Oxide Synthase Type II; Obesity; Oxidative Stress; PC12 Cells; Rats; Time Factors; Tumor Necrosis Factor-alpha; Xanthophylls