fucoxanthin and Inflammation

Owing to its unique structure and properties, fucoxanthin (FX), a carotenoid, has attracted significant attention. There have been numerous studies that demonstrate FX's anti-inflammatory, antioxidant, antitumor, and anti-obesity properties against inflammation-related diseases. There is no consensus, however, regarding the molecular mechanisms underlying this phenomenon. In this review, we summarize the potential health benefits of FX in inflammatory-related diseases, from the perspective of animal and cellular experiments, to provide insights for future research on FX. Previous work in our lab has demonstrated that FX remarkably decreased LPS-induced inflammation and improved survival in septic mice. Further investigation of the activity of FX against a wide range of diseases will require new approaches to uncover its molecular mechanism. This review will provide an outline of the current state of knowledge regarding FX application in the clinical setting and suggest future directions to implement FX as a therapeutic ingredient in pharmaceutical sciences in order to develop it into a treatment strategy against inflammation-associated disorders.

Topics: Animals; Antioxidants; Inflammation; Mice; Obesity; Xanthophylls

Fucoxanthin, a natural product of carotenoids, is a potential drug source obtained from marine algae. The special chemical structure of fucoxanthin has equipped it with a variety of biological activities. Several studies have indicated that fucoxanthin has a potential protective effect on a variety of inflammation-related diseases. This mechanism may be related to fucoxanthin's strong antioxidant capacity and gut microbiota regulation. The key molecules that require consideration include nuclear factor erythroid 2-related factor 2, Akt serine/threonine kinase/phosphatidylinositol-3-kinase, extracellular signal-regulated kinase, adenosine monophosphate (AMP)-dependent protein kinase, cAMP response element binding protein, and peroxisome proliferator-activated receptorγcoactivator-1α. The study summarizes the recent progress in the research based on the protective effect of fucoxanthin and its related molecular mechanism, in addition to the potential use of fucoxanthin as a promising compound for human inflammation-related diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Gastrointestinal Microbiome; Humans; Inflammation; 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) has been reported to reduce mortality in mouse models of sepsis, but its exact cause remains to be determined. In the present study, we evaluated the immunomodulatory properties of FX in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our results showed that FX could not only suppress the immune activation responses caused by LPS primary stimulation, but also antagonize LPS restimulation-induced immunosuppression in macrophages. The immunomodulatory capabilities of FX was mainly demonstrated by regulating the production of the inflammatory mediator under different LPS stimuli. Furthermore, we found that adenosine monophosphate-activated protein kinase (AMPK) activation was required for FX's anti-inflammatory and anti-immunosuppressive activities. Our results complement existing data supporting the clinical potential for FX in treating sepsis.

Topics: Animals; Immunosuppression Therapy; Inflammation; Lipopolysaccharides; Macrophages; Mice; Sepsis

Hepatotoxic contaminants such as zearalenone (ZEA) are widely present in foods. Marine algae have a wide range of potential applications in pharmaceuticals, cosmetics, and food products. Research is ongoing to develop treatments and products based on the compounds found in algae. Fucoxanthin (FXN) is a brown-algae-derived dietary compound that is reported to prevent hepatotoxicity caused by ZEA. This compound has multiple biological functions, including anti-diabetic, anti-obesity, anti-microbial, and anti-cancer properties. Furthermore, FXN is a powerful antioxidant. In this study, we examined the effects of FXN on ZEA-induced stress and inflammation in HepG2 cells. MTT assays, ROS generation assays, Western blots, and apoptosis analysis were used to evaluate the effects of FXN on ZEA-induced HepG2 cell inflammation. Pre-incubation with FXN reduced the cytotoxicity of ZEA toward HepG2 cells. FXN inhibited the ZEA-induced production of pro-inflammatory cytokines, including IL-1 β, IL-6, and TNF-α. Moreover, FXN increased HO-1 expression in HepG2 by activating the PI3K/AKT/NRF2 signaling pathway. In conclusion, FXN inhibits ZEA-induced inflammation and oxidative stress in hepatocytes by targeting Nrf2 via activating PI3K/AKT signaling.

Topics: Apoptosis; Humans; Inflammation; NF-E2-Related Factor 2; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Zearalenone

Suppression of excessive inflammatory responses improves the survival of patients with sepsis. We previously illustrated the anti-inflammatory effects of fucoxanthin (FX), a natural carotenoid isolated from brown algae; nevertheless, the underlying mechanism remains unknown. In this study, we examine the mechanism of the action of FX by targeting interferon regulatory factor 3 (IRF3) to inhibit inflammatory response. We observed that FX regulated innate immunity by inhibiting IRF3 phosphorylation

Topics: Animals; Inflammation; Interferon Regulatory Factor-3; Mice; Sepsis; Xanthophylls

Macrophages play an important role in managing the onset and progression of chronic inflammatory diseases. The primary objective of this study is to explore the antioxidant potential and anti-inflammatory properties of

Topics: Animals; Antioxidants; China; Ethnicity; Humans; Inflammation; Lipopolysaccharides; Macrophages; Mice; RAW 264.7 Cells; Sargassum

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-1β 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.

Topics: AMP-Activated Protein Kinases; Animals; Fatty Acids, Nonesterified; Inflammation; Lipid Metabolism; Liver; Mice; NF-E2-Related Factor 2; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Signal Transduction; Toll-Like Receptor 4; Xanthophylls

The most common cause of intra-abdominal adhesion (IAA) is previous abdominal surgery and mortality. IAA can cause serious complications such as chronic abdominal pain, ileus, and infertility. Approximately 3% of all laparotomies are related to adhesions. IAA reduces the quality of life of the patient, causes morbidity, and increases health expenditures. In this study, we aimed to investigate the preventive effect of fucoxanthin (Fx) on IAA in the intra-abdominal surgical adhesion model that experimentally created in rats.. This study used 21 Sprague-Dawley rats divided into three groups. After anesthesia, the abdomen was opened, the cecum and right abdominal wall were damaged with a sterile toothbrush until petechiae bleeding was seen. No additional action was taken to the control group. In the sham group, 5 cc saline solution was released into the peritoneum before the abdomen was closed. In the Fx group, 35 mg/kg Fx was instilled intraperitoneally and the abdomen was closed. On the 21st post-operative day, all subjects were anesthetized with standard anesthesia. Macroscopic adhesions were quantitatively evaluated according to the Mazuji classifica-tion. The cecum anterior wall and parietal peritoneum were excised for pathological sampling. A pathologist, unaware of the groups, evaluated inflammation, fibroblastic activity, and vascular proliferation. In addition, serum tumor necrosis factor-alpha (TNF-α) and interleukin-10 levels were measured.. No rat was lost during the study period. Congenital adhesion was not observed in any of the subjects at the first laparo-tomy. Adhesion was significantly less macroscopically in the Fx group compared to the control and sham group (p<0.001 and p<0.001). Fibroblastic activity was found to be significantly less in the Fx group compared to the sham and control groups (p<0.001 and p<0.001). Vascular proliferation was found to be significantly less in the Fx group than in the sham and control groups (p<0.001 and p<0.001). The inflammation score was significantly lower in the Fx group compared to the other two groups (p<0.001 and p<0.001). The inflam-mation score in the sham group was lower than the control group and was statistically significant (p<0.001). TNF-α level was found to be statistically significantly lower in the Fx group compared to the sham and control groups (p<0.001 and p<0.001).. As a result of experimental study, we can say that Fx is effective in preventing IAAs and decreases the level of TNF-α, a pro-inflammatory cytokine.

Topics: Abdominal Wall; Animals; Humans; Inflammation; Postoperative Complications; Quality of Life; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Tumor Necrosis Factor-alpha; Xanthophylls

Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are mediated by the activation of various kinds of signaling pathways in the innate immune system. Particularly, NF-κB and NLRP3 inflammasome signaling are involved in the production and secretion of these cytokines. Each signaling is participated in the two steps necessary for IL-1β, a representative pro-inflammatory cytokine, to be processed into a form secreted by cells. In the priming step stimulated by LPS, pro-IL-1β is synthesized through NF-κB activation. Pro-IL-1β cleavages into mature IL-1β by formed NLRP3 inflammasome in the activation step induced by ATP. The mature form of IL-1β is subsequently secreted out of the cell, causing inflammation. Moreover, IL-6 and TNF-α are known to increase in NLRP3 inflammasome-mediated conditions. Here, we found that fucoxanthin, one of the major components of Phaeodactylum tricornutum, has an inhibitory effect on NF-κB and NLRP3 inflammasome activation induced by the combination of LPS and ATP in bone marrow-derived immune cells as well as astrocytes. Fucoxanthin, which is abundant in the EtOH fraction of Phaeodactylum tricornutum extracts, has shown to have less cell toxicity and found to decrease the production of major pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Fucoxanthin has also shown to suppress the expression of cleaved caspase-1 and the oligomerization of ASC, which are the main components of the NLRP3 inflammasome. Furthermore, phosphorylated IκBα and pro-IL-1β expression decreased in the presence of fucoxanthin, suggesting that fucoxanthin can negatively regulate the priming step of inflammasome signaling. Thus, our results provide reliable evidence that fucoxanthin may serve as a key candidate in the development of potential therapeutic agents for inflammatory diseases as well as neurodegenerative diseases caused by NF-κB and NLRP3 inflammasome activation.

Topics: Astrocytes; Cytokines; Dendritic Cells; Humans; Inflammasomes; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Macrophages; Microalgae; Molecular Targeted Therapy; Neurodegenerative Diseases; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Phytotherapy; Signal Transduction; Tumor Necrosis Factor-alpha; Xanthophylls

Anti-inflammatory and antioxidant effects of fucoxanthin (FCX), a xanthophyll carotenoid, have been suggested. However, underlying mechanisms are elusive. The objective of this study was to elucidate the mechanisms by which FCX and its metabolites inhibit lipopolysaccharide (LPS)-induced inflammation and oxidative stress in macrophages.. The effects of the FCX on mRNA and protein expression of pro-inflammatory cytokines and antioxidant genes, and reactive oxygen species (ROS) accumulation were determined in RAW 264.7 macrophages. A potential role of FCX in the modulation of phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear E2-related factor 2 (NRF2) axis was evaluated.. FCX significantly decreased LPS-induced interleukin (Il)6, Il1b, and tumor necrosis factor α (Tnf) mRNA abundance and TNFα secretion. FCX attenuated LPS or tert-butyl-hydroperoxide-induced ROS accumulation with concomitant increases in the expression of antioxidant enzymes. Also, trolox equivalent antioxidant capacity assay demonstrated that FCX had a potent free radical scavenging property. FCX markedly increased nuclear translocation of NRF2 in LPS-treated macrophages, consequently inducing its target gene expression. Interestingly, the effect of FCX on NRF2 nuclear translocation was noticeably diminished by LY294002, an inhibitor of PI3K, but not by inhibitors of mitogen-activated protein kinases. Phosphorylation of AKT, a downstream element of PI3K, was also markedly increased by FCX. FCX metabolites, such as fucoxanthinol and amarouciaxanthin A, significantly attenuated LPS-induced ROS accumulation and pro-inflammatory cytokine expression.. FCX exerts anti-inflammatory and antioxidant effects by the activation of NRF2 in the macrophages activated by LPS, which is mediated, at least in part, through the PI3K/AKT pathway.

Topics: Humans; Inflammation; Lipopolysaccharides; Macrophages; NF-E2-Related Factor 2; Oxidative Stress; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Xanthophylls

Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg-1 day-1, i.p) and exposed to γ-radiation (2.5 Gy week-1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1β and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues' architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.

Topics: Animals; Antioxidants; Apelin Receptors; Gamma Rays; Inflammation; Intercellular Signaling Peptides and Proteins; Kidney; L-Lactate Dehydrogenase; Liver; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; NF-kappa B; Organ Specificity; Oxidants; Signal Transduction; Tissue Inhibitor of Metalloproteinase-1; Whole-Body Irradiation; Xanthophylls

Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.

Topics: Animals; Asthma; Cell Line; Cytokines; Epithelial Cells; Female; Humans; Inflammation; Mice; Mice, Inbred BALB C; Oxidative Stress; Reactive Oxygen Species; Respiratory Hypersensitivity; Xanthophylls

In this study, we aimed to examine the effects of fucoxanthin on inflammation triggered by palmitate in macrophages. Raw 264.7 cells were treated with palmitate with or without fucoxanthin co-treatment. Fucoxanthin greatly alleviated palmitate-induced decrease in cell viability and loss of mitochondrial membrane potential. Fucoxanthin also significantly attenuated the palmitate-induced transcriptional expression of Il-6, Il-1β, Tnfα and Nlrp3 inflammasomes and increased the expression of Tgfb. In addition, fucoxanthin decreased triglyceride accumulation induced by palmitate through enhancing the expression of Cpt1a, Pparg and other lipid metabolism genes. Inhibition of CPT1a by etomoxir attenuated the anti-inflammatory effect of fucoxanthin. Furthermore, fucoxanthin increased AMPK phosphorylation and AMPKa1 knockdown by its specific siRNA diminished protective function. In addition, fucoxanthin restored palmitate-mediated mitochondrial dysfunction and improved mitophagy-related gene expression. These findings suggest that fucoxanthin could attenuate free fatty acid-induced inflammation in macrophages through modulating lipid metabolism and mitigating mitochondrial dysfunction.

Topics: Animals; Cell Survival; Fatty Acids, Nonesterified; Gene Expression; Inflammasomes; Inflammation; Interleukin-1beta; Interleukin-6; Lipid Metabolism; Macrophages; Membrane Potential, Mitochondrial; Mice; Mitochondria; Mitophagy; NLR Family, Pyrin Domain-Containing 3 Protein; Palmitates; RAW 264.7 Cells; Tumor Necrosis Factor-alpha; 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

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

Fucoxanthin, a potent carotenoid present in various natural sources especially from seaweeds; it exhibits several biological effects like anti-neoplastic, anti-mutagenic, anti-diabetic, anti-obesity and anti-inflammatory actions. Fucoxanthin role in chemoprevention of lung cancer in mouse model induced using benzo(a)pyrene [B(a)P] has been presented here. Oral administration of fucoxanthin with and without B(a)P were studied, the results from our study shows that fucoxanthin significantly decreased tumor progression in mice exposed to B(a)P, the obtained data were correlated with increased antioxidant, apoptosis and decreased tumour marker and anti-apoptotic molecules. With respect to apoptosis, fucoxanthin treated animals shows increased apoptosis compared to tumor induced mice by increased expression of caspase 9 and 3 and decreased expression of anti-apoptotic Bcl2 protein. Finally, histopathological and immuno histochemical analysis also revealed that fucoxanthin shows potent anticancer agent by bringing back the damaged tissue treated with B(a)P and also decreases the expression of PCNA in cancer induced mice. The anticancer effect of fucoxanthin may be attributed by several independent mechanisms which play a important roles in the prevention of cancer development, there is also substantial evidences to show that fucoxanthin acts indirectly by increasing the antioxidant capacity of affected tissue and prepared to cope up with oxidative stress which is proved in our study. Thus from our study it is clearly established that fucoxanthin act as a persuasive anticancer drug against lung cancer.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Benzo(a)pyrene; Inflammation; Lung Neoplasms; Male; Mice; Signal Transduction; Xanthophylls

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.

Topics: Animals; Anti-Asthmatic Agents; Antioxidants; Asthma; Biomarkers; Bronchoalveolar Lavage Fluid; Cytokines; Inflammation; Male; Mice; Ovalbumin; Reactive Oxygen Species; 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

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

The objective of the present study was to investigate the effect of the fucoxanthin (FUCO) alone and in combination with glucosamine hydrochloride (GAH) on carrageenan/kaolin-induced inflammatory arthritis model in rats and to explore its underlying mechanisms. Joint swelling, muscle weight ratio (%), histopathological examination and scoring, and proteoglycan degradation were examined. Pro-inflammatory interleukin (IL-1β) and tumor necrosis (TNF-α) levels, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase(iNOS) protein expression and nitric oxide (NO) level in knee synovial tissue extract were analyzed using enzyme-linked immunosorbent assay, western blotting analysis, and Griess reagent assay, respectively. FUCO and FUCO + GAH not only may significantly reduce degrees of knee joint swelling and prevent against muscle atrophy, but also may significantly attenuate inflammation in synovial tissue, cartilage erosion, and proteoglycan loss. The efficacies of FUCO + GAH were stronger than that of GAH or FUCO. FUCO alone and FUCO + GAH can significantly inhibit upregulation of COX-2 and iNOS protein expressions, decrease of IL-1β and TNF-α levels, and reduce NO production in knee synovial tissue extract. These results indicated that FUCO is an effective anti-arthritis agent through an antiinflammation mechanism. FUCO may enhance therapeutic effect of GAH on rat arthritis through mechanism of antiinflammation.

Topics: Animals; Arthritis, Experimental; Carrageenan; Cyclooxygenase 2; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Glucosamine; Inflammation; Inflammation Mediators; Interleukin-1beta; Kaolin; Knee Joint; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Proteoglycans; Rats; Rats, Sprague-Dawley; Synovial Membrane; Tumor Necrosis Factor-alpha; Xanthophylls

Peridinin and fucoxanthin, which are natural carotenoids isolated from a symbiotic dinoflagellate, Symbiodinium sp., and a brown alga, Petalonia fascia, respectively, were compared for inhibitory effects on delayed-type hypersensitivity in mice. The number of eosinophils at the site of inflammation and in peripheral blood was compared for the administration of peridinin and fucoxanthin applied by painting and intraperitoneally. Peridinin, but not the structurally-related fucoxanthin, significantly suppressed the number of eosinophils in both the ear lobe and peripheral blood. Furthermore, peridinin applied topically, but not administered intraperitoneally, suppressed the level of eotaxin in the ears of sensitized mice. Fucoxanthin weakly suppressed the concentration of eotaxin in ears only by intraperitoneal administration. Although both carotenoids inhibited the migration of eosinophils toward eotaxin, the inhibitory effect of peridinin was higher than that of fucoxanthin. Peridinin may be a potential agent for suppressing allergic inflammatory responses, such as atopic dermatitis, in which eosinophils play a major role in the increase of inflammation.

Topics: Administration, Topical; Animals; Carotenoids; Dinoflagellida; Eosinophilia; Eosinophils; Female; Inflammation; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Transgenic; Phaeophyceae; Xanthophylls

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease that slowly destroys memory and thinking skills. In the brains of AD patients, signs of neuronal degeneration are accompanied by markers of microglial activation and inflammation as well as oxidant damage. This study tested the hypothesis that fucoxanthin, which is known to exert a variety of pharmacological properties, would ameliorate oxidative stress and inflammation in amyloid-β42 (Aβ42)-induced BV2 microglia cells. It was found that fucoxanthin treatment attenuated pro-inflammatory secretion in BV2 cells as determined by ELISA analysis. Suppressive effects of fucoxanthin on the phosphorylation mitogen-activated protein kinase (MAPK) pathway were confirmed. Moreover, fucoxanthin was able to inhibit free radical-induced DNA oxidation in BV2 cells. This effect was associated with a significant reduction of intracellular reactive oxygen species (ROS) formation and recovery of antioxidative enzymes. The findings in this study suggest that fucoxanthin may serve as a negative feedback regulator of inflammation and oxidative stress in BV2 cells and thereby may protect neuronal cells from neurotoxic mediators released by microglia.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cell Line; Cell Proliferation; Cytokines; Dinoprostone; Inflammation; Mice; Microglia; Mitogen-Activated Protein Kinases; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Xanthophylls