Glyconutrients

Fucoidan, a sulfated polysaccharide extracted from brown algae, exhibits anti-cancer activity. However, the effects and mechanism of fucoidan-induced apoptosis via endoplasmic reticulum (ER) stress is unclear. In this study, we demonstrated that fucoidan prevents tumorigenesis and reduces tumor size in LLC1-xenograft male C57BL/6 mice. Fucoidan induces an ER stress response by activating the PERK-ATF4-CHOP pathway, resulting in apoptotic cell death in vitro and in vivo. Furthermore, ATF4 knockdown abolishes fucoidan-induced CHOP expression and rescues cell viability. Specifically, fucoidan increases intracellular reactive oxygen species (ROS), which increase ATF4 and CHOP in lung cancer cells. Using the ROS scavenger N-acetyl-l-cysteine (NAC), we found that ROS generation is involved in fucoidan-induced ER stress-mediated apoptosis. Moreover, via Toll-like receptor 4 (TLR4) knockdown, we demonstrated that fucoidan-induced ROS and CHOP expression were attenuated. Our study is the first to identify a novel mechanism for the antitumor activity of fucoidan. We showed that fucoidan inhibits tumor viability by activating the TLR4/ROS/ER stress axis and the downstream PERK-ATF4-CHOP pathway, leading to apoptosis and suppression of lung cancer cell progression. Together, these results indicate that fucoidan is a potential preventive and therapeutic agent for lung cancer that acts via activation of ROS-dependent ER stress pathways.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. As the aging population is increasing, AD is becoming one of the leading causes of disability and death among the elderly. However, currently there is no cure for this disease. Fucoidan is a complex sulfated polysaccharide ma

Multiple myeloma (MM) remains an incurable hematological neoplasms. Our previous studies showed that Fucoidan possessed anti-myeloma effect by inducing apoptosis and inhibiting invasion of myeloma cells. In this study, we evaluated the effect of Fucoidan on angiogenesis induced by human myeloma cells and elucidated its possible mechanisms. Multiple myeloma cells were treated with Fucoidan at different concentrations, then the conditioned medium (CM) was collected. The levels of VEGF in the CM were tested by ELISA. The results showed that Fucoidan significantly decreased VEGF secretion by RPMI-8226 and U266 cells. The tube formation assay and migration test on human umbilical vein endothelial cells (HUVECs) were used to examine the effect of Fucoidan on angiogenesis induced by human myeloma cells. The results showed that Fucoidan decreased HUVECs formed tube structures and inhibited HUVECs migration, and suppressed the angiogenic ability of multiple myeloma RPMI-8226 and U266 cells in a dose-dependent manner. The study also showed that Fucoidan downregulated the expression of several kinds of proteins, which may be correlated with the reduction of angiogenesis induced by myeloma cells. Moreover, results were compared from normoxic and hypoxic conditions, they showed that Fucoidan had anti-angiogenic activity. Furthermore, in a multiple myeloma xenograft mouse model, it indicated that Fucoidan negatively affected tumor growth and angiogenesis in vivo. In conclusion, our results demonstrate that Fucoidan was able to interfere with angiogenesis of multiple myeloma cells both in vitro and in vivo and may have a substantial potential in the treatment of MM.

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been used in traditional Chinese herbal medicine to treat thyroid tumors for many years. Although a number of its cellular effects have been investigated, the role of fucoidan in molecular signaling, particularly in Ca2+ signaling …

In tumor microenvironment, macrophages as a polarized M2 population promote tumor progression via releasing multiple cytokines and chemokines. A brown seaweed fucose-rich polysaccharide, fucoidan has antitumor activity and immune modulation through affecting tumor cells and lymphocytes. Here, we focused on the effect of fucoidan on macrophages especially M2 subtype. Our results demonstrated that fucoidan down-regulated partial cytokines and chemokines, especially a M2-type chemokine CCL22. Furthermore, fucoidan inhibited tumor cells migration and CD4+ T lymphocytes, especially Treg cells, recruitment induced by M2 macrophages conditioned medium through suppression of CCL22. Mechanismly, fucoidan inhibited CCL22 via suppressing p65-NF-κB phosphorylation and nuclear translocation. In addition, p38-MAPK and PI3K-AKT also affected the expression of CCL22 through differential modulation of NF-κB transcriptional activity. Taken together, we reveal an interesting result that fucoidan can inhibit tumor cell migration and lymphocytes recruitment by suppressing CCL22 in M2 macrophages via NF-κB-dependent transcription, which may be a novel and promising mechanism for tumor immunotherapy.

Fucoidan, a sulfated polysaccharide, is an active component found in various species of seaweed. Although this compound has a strong anti-inflammatory activity, the underlying mechanisms exerted by fucoidan have not been fully elucidated. In the present study, the anti-inflammatory effects of fucoidan on lipopolysaccharide (LPS)-stimulated macrophages and zebrafish larvae were examined. The present data indicated that fucoidan significantly suppressed the secretion of pro-inflammatory mediators including nitric oxide (NO ) and prostaglandin E2 (PGE2), and cytokines, such as tumor necrosis factor-α and interleukin-1β in RAW 264.7 macrophages without any significant cytotoxicity, the protective effects of which were accompanied by a marked reduction in their regulatory gene expression at the transcription levels. Fucoidan also inhibited translocation of the nuclear factor-kappa B from the cytoplasm to the nucleus and attenuated LPS-induced production of intracellular reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, fucoidan reduced NO and PGE2 production and ROS accumulation in LPS-stimulated zebrafish larvae, which was associated with a diminished recruitment of neutrophils and macrophages. Based on the results of this study, we suggest that fucoidan has excellent potential as a therapeutic agent for inflammatory disorders.

Studies have been focused on natural products with antibacterial and anti-inflammatory activities, such as fucoidan. Many in vivo studies have evaluat…

Studies have been focused on natural products with antibacterial and anti-inflammatory activities, such as fucoidan. Many in vivo studies have evaluat…

Lymphangiogenesis is one of the promoters of tumor lymphatic metastasis. Fucoidan which is a fucose-enriched sulfated polysaccharide has effect on various pharmacological activities including anti-metastasis activity. However, the inhibitory effect of fucoidan on lymphangiogenesis remains unclear. H …

Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effe

Retention after treatment and effective anchorage control are two essential factors in orthodontics. Fucoidan treatment inhibits orthodontic tooth movement and enhances the stability of teeth after m...

Background: Fucoidan is a natural sulfated polysaccharide which exists mainly in the cell wall matrix of various species of brown seaweed. Various forms of fucoidan have also been recognized in some marine invertebrates such as sea urchins and sea cucumbers. Fucoidan inhibits the spread of cancerous cells by preventing the adhesion of tumor cells to the extracellular matrix in addition to inducing apoptosis, or programmed self-destruction, in human T-cells infected by T-cells leukemia virus type I (HTLV-1) which causes adult T-cell leukemia. The polysaccharide has also been shown to stimulate the phagocytic action of macrophages and synthesis of several immune cell types, which increases protection against infection. Fucoidan gives the immune system a big boost by enhancing phagocytosis. Additionally, it increases the number of mature white blood cells which are circulating in the body, thereby bolstering the first line of defense against infections and diseases. Moreover, fucoidan has anti-coagulant, anti-thrombotic, anti-inflammatory, antioxidant, anti-allergic, anti-tumor properties and also many others. Methods and Results: In this study, we investigated whether fucoidan is able to alleviate the vascular remodeling process triggered by immunological stimuli in rat allogenic aorta transplantation model, in addition to the evaluated potential mechanisms responsible for the observed effects. Our rat aorta transplantation model was subjected to intraperitoneal or oral treatment with fucoidan or placebo. The results of our study demonstrated that fucoidan inhibits endointimal hyperplasia formation and vascular modulation. In particular, intraperitoneal and oral administration of fucoidan reduced neointima formation in allografts retrieved 8 weeks after transplantation. Moreover, both treatments with fucoidan reduced the number of smooth muscle (SM) a-actin positive cells in intima and adventitia, decreased percentage of macrophages in intima and media, and increased the number of leukocytes in media of the allografts. Fucoidan treatments have also caused reduction in apoptosis in allograft intima and media. Conclusion: Through our study, we demonstrated the inhibitory effect of fucoidan on vascular remodeling in transplant vasculopathy within rats. Our study is the first report of the beneficial effects of fucoidan oral administration on this process, which may have important clinical implications and result in a better understanding of vascular remodeling.  Keywords : fucoidan, transplant vasculopathy, vascular remodeling

Background This study was to investigate the effect and its possible mechanism of fucoidan on the development of spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice. Methods 7-week-old NOD mice were randomly divided into three groups: control group, low-dose (300 mg/kg) and high-dose (600 mg/kg) fucoidan-treatment groups. After 5 weeks of treatment, 10 mice per group were randomly selected to be sacrificed after feces collection. The remaining 12 mice per group were fed until 26 weeks of age to assess the incidence of diabetes. Results Treatment with fucoidan increased serum insulin level, delayed the onset and decreased the development of diabetes in NOD mice. Fucoidan reduced the levels of strong Th1 proinflammatory cytokines, but induced Th2-bias ed. cytokine response. And dentridic cells (DCs) in fucoidan treatment group were characterized as low expression of MHC class II and CD86 molecules. TLR4 expressions and the downstream molecules in pancreas were down-regulated in fucoidan-treated groups. There were significant differences in the composition of gut flora between NOD control group and fucoidan group. Lactobacillus and Akkermansia were significantly enriched in fucoidan group. Conclusions Fucoidan could prevent the development of autoimmune diabetes in NOD mice via regulating DC/Treg induced immune tolerance, improving gut microecology, down-regulating TLR4 signaling pathway, and maintaining pancreatic internal environment.

Fucoidan is a sulfated polysaccharide that is primarily extracted from brown seaweeds which has been broadly studied in recent years due to its numerous biological properties, including anticoagulant, antithrombotic, antitumor, and antiviral activities. In this study, we investigated whether fucoidan has the ability to attenuate the expression of pro-inflammatory mediators such as NO, prostaglandin E2 (PGE2), TNF-α, and IL-1β in LPS-stimulated RAW 264.7 macrophage cells. Fucoidan inhibited the expression of LPS-induced pro-inflammatory mediators including NO, PGE2, TNF-α, and IL-1β. In addition, gene expression of iNOS, cyclooxygenase-2 (COX-2), TNF-α, and IL-1β was inhibited both at mRNA and protein levels by fucoidan treatment, without any cytotoxic effect. Moreover, fucoidan significantly inhibited LPS-induced NF-κB activity NF-κB translocation into the nucleus by preventing the degradation of iκB-α. Taken together, these results indicate that fucoidan downregulates the expression of pro-inflammatory genes involved in the synthesis of NO, PGE2, TNF-α, and IL-1β in LPS-stimulated RAW 264.7 macrophage cells by suppressing NF-κB activity.

Fucoidans (FUC) are organic sulfated polysaccharides from natural seaweeds with multiple biological actions. The current study was performed to assess the chemoprotective, antioxidant, and anti-inflammatory effects of FUC from Laminaria japonicum against diazinon (DZN)-induced injuries to rat cardiac, hepatic, and renal tissues. Forty male Wistar rats were assigned into five groups, receiving saline, oral FUC 200 mg/kg/day, subcutaneous DZN 20 mg/kg/day, DZN plus FUC 100 mg/kg/day, or DZN plus FUC 200 mg/kg/day (each treatment was given daily for 4 weeks). Data analysis showed that DZN-intoxicated rats exhibited significantly higher (p

Fucoidan is a complex of polysaccharides showing antitumor and immunomodulation properties. Our previous studies found its regulation to myeloid immune cells, including macrophages. Aberrant infiltration and functions of macrophages are commonly found in oral squamous cell carcinoma (OSCC). In this study, we analyzed the effects of fucoidan on invasion of OSCC cells, and their regulation to macrophages, trying to evaluate its role as a potential therapy for OSCC. CAL27 and THP-1-derived macrophages were used as models for OSCC cells and tumor-infiltrated macrophages in the in vitro study, respectively. The effects of fucoidan on invasion of OSCC cells and their recruitment to macrophages were analyzed by transwell assay. KIF4A siRNA transfection was performed to investigate its role in fucoidan-modulated OSCC cells invasion. CCL3-neutralizing antibody was added into the conditioned medium of OSCC cells to evaluate its role in fucoidan-mediated macrophages recruitment and re-education. Fucoidan reduced the invasive potential of CAL27 cells with a decrease of MMP-2 and KIF4A transcription. KIF4A knockdown in CAL27 cells led to decreased invasion and MMP-2 expression. The conditioned medium of fucoidan-treated CAL27 cells promoted recruitment and inflammatory cytokines secretion on THP-1-derived macrophages. Further analysis found that fucoidan increased CCL3 production in CAL27 cells. Blocking CCL3 expression reversed the effects of fucoidan on macrophage recruitment and re-education. Our study found that fucoidan regulated the invasion of OSCC cells and also their recruiting and re-educating effects on macrophages, suggesting it could be a complementary approach in the treatment of OSCC.

Fucoidan is a complex of polysaccharides showing antitumor and immunomodulation properties. Our previous studies found its regulation to myeloid immune cells, including macrophages. Aberrant infiltration and functions of macrophages are commonly found in oral squamous cell carcinoma (OSCC). In this study, we analyzed the effects of fucoidan on invasion of OSCC cells, and their regulation to macrophages, trying to evaluate its role as a potential therapy for OSCC. CAL27 and THP-1-derived macrophages were used as models for OSCC cells and tumor-infiltrated macrophages in the in vitro study, respectively. The effects of fucoidan on invasion of OSCC cells and their recruitment to macrophages were analyzed by transwell assay. KIF4A siRNA transfection was performed to investigate its role in fucoidan-modulated OSCC cells invasion. CCL3-neutralizing antibody was added into the conditioned medium of OSCC cells to evaluate its role in fucoidan-mediated macrophages recruitment and re-education. Fucoidan reduced the invasive potential of CAL27 cells with a decrease of MMP-2 and KIF4A transcription. KIF4A knockdown in CAL27 cells led to decreased invasion and MMP-2 expression. The conditioned medium of fucoidan-treated CAL27 cells promoted recruitment and inflammatory cytokines secretion on THP-1-derived macrophages. Further analysis found that fucoidan increased CCL3 production in CAL27 cells. Blocking CCL3 expression reversed the effects of fucoidan on macrophage recruitment and re-education. Our study found that fucoidan regulated the invasion of OSCC cells and also their recruiting and re-educating effects on macrophages, suggesting it could be a complementary approach in the treatment of OSCC.

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Fucoidan is a natural derived compound found in different species of brown algae and in some animals, that has gained attention for its anticancer properties. However, the exact mechanism of action is currently unknown. Therefore, this review will address fucoidans structure, the bioavailability, an …

Fucoidans are complex polysaccharides derived from brown seaweeds which consist of considerable proportions of L-fucose and other monosaccharides, and sulphated ester residues. The search for novel and natural bioproduct drugs (due to toxicity issues associated with chemotherapeutics) has led to the …

We examined the effect of fucoidan, an immune modulator, on the phagocytic capacity of porcine peripheral blood polymorphonuclear cells (PMNs) exposed…

Mitochondria are considered to be the powerhouses of cells. They are the most commonly damaged organelles within dopaminergic neurons in patients with Parkinson's disease (PD). Despite the importance of protecting neuronal mitochondria in PD patients, the detailed mechanisms underlying mitochondrial …

Abstract. The sulfated polysaccharide fucoidan displays excellent anticancer properties with low toxicity in many kinds of cancers. However, its detailed pharma

Cisplatin-based therapy is a traditional, clinical treatment for cancers, including lung cancer. In this study, we found that sequential therapy, i.e.…

Cancer is most common in worldwide and badly threaten to human’s life. Unfortunately drugs, which are used for cancer therapy, are toxic and affect not only cancer cells but also normal cells and...

Hepatocellular carcinoma (HCC) is a fast growing tumor associated with a high tendency for vascular invasion and distant metastasis. Recently, we repo…

Osteogenesis and angiogenesis, including cell–cell communication between blood vessel cells and bone cells, are essential for bone repair. Fucoidan is a chemical compound that has a variety of biolog...