Fucoidan is a functional food that possesses various biological activities. This study aims to determine the effects of fucoidan from Undaria pinnatif…

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and antioxidant ac…

Fucoidans (FUCs) are sulfated polysaccharides that have a wide range of bioactivities. The current study was designed to evaluate the antioxidant potential of FUC against microcystin-LR (MC-LR)-induced toxicity. Five mice groups (n = 8) were used. Group 1 received saline, Group 2 received oral FUC 1 …

The current study was carried out to evaluate the ameliorative effect of fucoidan against aflatoxicosis-induced hepatorenal toxicity in streptozotocin-induced diabetic rats. Sixty-four Wister albino male rats were randomly assigned into eight groups (8 rats each) that received normal saline, fucoidan (FUC) at 100 mg/kg/day orally for 4 weeks, streptozotocin (STZ) at 50 mg/kg/i.p. single dose, STZ plus FUC, aflatoxin B1 (AFB1) at 50 μg/kg/i.p. after one month of the beginning of the experiment for 2 weeks, AFB1 plus FUC, STZ plus AFB1, or STZ plus AFB1 and FUC. Injection of rats with STZ induced hyperglycemia. Rats with STZ-induced diabetes, with or without AFB1 intoxication, had significantly elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of serum urea, creatinine, cholesterol, 8-oxo-2-deoxyguanosine, interleukin-1β, interleukin-6, and tumor necrosis factor-α. In addition, these rats exhibited increased lipid peroxidation and reduced glutathione concentration and activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes in the hepatic and renal tissues. In contrast, administration of FUC to diabetic rats, with or without AFB1 intoxication, ameliorated the altered serum parameters, reduced oxidative stress, DNA damage, and inflammatory biomarkers, and enhanced the antioxidant defense system in the hepatic and renal tissues. These results indicated that FUC ameliorated diabetes and AFB1-induced hepatorenal injuries through alleviating oxidative stress, DNA damage, and inflammation.

The proposed mechanisms of the protective effect of FO against diabetes. Fucoidan ameliorates pancreatic β-cell damage and the impaired insulin synthesis by activating Sirt-1-mediated processes under...

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.

There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues ...

In rats, FUC and GOS supplementation improved serum dyslipidemia, gut microbiota, BSH activity, and bile acid metabolism-related pathways. In vitro, GOS and FUC supplementation increased L. casei DM8121's BSH activity.

Obesity is an escalating global pandemic posing a serious threat to human health. The intervention therapy using weight-reducing drugs, accompanied by lifestyle modification, is a strategy for the treatment of obesity. In the present study, we explored the role of fucoidan, a seaweed compound, on high-fat diet (HFD)-induced obesity in mice. We found that fucoidan treatment significantly reduced the body fat and caused redistribution of visceral and subcutaneous fat in HFD-fed mice. Meanwhile, fucoidan treatment inhibited adipocyte hypertrophy and inflammation in adipose tissue. Collectively, these results suggest that fucoidan may be a promising treatment for obesity and obesity-induced complications.

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 has received much attention in healthy food and biomedicine owing to their unique (bio)physicochemical properties, particularly antibacterial…

Fucoidan is a bio-functional polysaccharide, mainly reported in brown seaweed. Diverse potential of fucoidan has created intense interest to review th…

Rupture of abdominal aortic aneurysm (AAA) is one of the leading causes of sudden death among the elderly. Most incidental AAAs are below the threshold for intervention at the time of detection; however, there is no evidence that commonly used cardiovascular drugs have clinical beneficial effects on AAA progression. Therefore, in addition to current cardiovascular risk-reducing treatments, an adjunctive medical therapy targeting the regulation of extracellular matrix metabolism is still required in the clinical setting.

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.

Background Radioiodine (RI) treatments can destroy the cellular components of salivary glands (SG) and disrupt their function. This study investigated whether fucoidan could attenuate radioiodine-induced SG dysfunction in a mouse model. Methods Female C57BL/6 mice (n = 36) were classified into three groups; i) a normal (control) group, ii) an RI-treated group (0.2 mCi/20 g mouse, administered orally), and iii) a fucoidan and RI-treated group. Mice in each group were classified into three subgroups and sacrificed at 2, 4, and 12 weeks after RI treatment. The measurements of salivary flow rates and lag times and histomorphologic examinations were performed, and apoptotic assays were conducted. Changes in salivary 99mTechnetium (Tc)-pertechnetate parameters using single-photon emission computed tomography were followed. Results Salivary flow rates and lag times in the fucoidan group were improved compared to the RI-treated group. Histologic examinations of SGs in the fucoidan group showed mucin-rich parenchymal areas and reduced periductal fibrosis as compared to the RI-treated group. Moreover, compared with the RI-treated group, fucoidan-treated groups showed evidence of cytoprotection, with a greater number of salivary epithelial cells and myoepithelial cells being observed. Fewer apoptotic cells were observed in the fucoidan group as compared to the RI group. The extent of 99mTc pertechnetate excretion in the fucoidan group was similar to that of the control group. Conclusion Our results demonstrate that fucoidan administration before RI treatment could attenuate RI-induced SG damage and provides a possible candidate for preventing SG damage induced by RI.

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 …

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 …

Marine organisms are sources of several natural compounds with potential clinical use. However, only a few marine-based pharmaceuticals have been approved for use due to limited knowledge on their biological activities. Here, we identified the functional role of fucoidan extracted from Fucus vesiculosus on ovarian cancer. Fucoidan increased the death of ES-2 and OV-90 cells, through a reduction in proliferation, cell cycle arrest, releases of cytochrome c, reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress. Additionally, fucoidan increased the concentration of cytosolic and mitochondrial calcium in both cells. The decrease of cell proliferation was controlled by the inactivation of PI3K and MAPK signaling cascades in ES-2 and OV-90 cells. In a toxicity assay with normal zebrafish larvae, fucoidan did not induce toxicity, cardiotoxicity, development, kinesis, and apoptosis at different concentrations. However, it disrupted tumor formation and vascular development in a zebrafish xenograft model and angiogenesis transgenic (Tg, fli1-eGFP) model, respectively. Collectively, the results indicate that fucoidan may be a novel pharmaceutical for the management of human ovarian cancer.

Fucoidan, a sulfated polysaccharide present in brown seaweed, has demonstrated anticancer activity in lung, breast, liver and colon cells. The insulin-like growth factor (IGF) signaling pathway regulates growth in HT-29 cells through the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Ras/Raf/extracellular signal-regulated kinase (ERK) pathways. The aim of the present study was to investigate whether fucoidan downregulates the IGF-IR signaling pathway in HT-29 human colon cancer cells. Fucoidan treatment (0-1,000 µg/ml) was administered for 24 h in HT-29 cells. First, we investigated IRS-1/PI3K/AKT pathway-related protein expression levels following treatment with fucoidan (0-500 µg/ml) using western blot analysis. Fucoidan significantly inhibited the expression of IGF-IR, PTEN, PI3K and AKT as well as their phosphorylated forms (p-IRS-1, p-PI3K and p-AKT). Next, we investigated the effects of fucoidan on Ras/Raf/ERK pathway‑related protein expression levels in HT-29 cells. Fucoidan significantly inhibited the expression of IGF-IR, Shc, Ras, SOS, Raf and MEK. HT-29 cells were then incubated in the presence of fucoidan (0 or 250 µg/ml), and IGF-I (10 nM) was added for 0 to 60 min. Immunoprecipitation (IP) experiments showed that fucoidan inhibited IGF-I-induced phosphorylation of IGF-IR, PI3K, Shc (IP, IGF-IR), and phosphorylated IRS-1 and PI3K (IP, IRS-1) compared to the control group. Western blot analysis showed that fucoidan inhibited the expression of IGF-I-induced p-IGF-IR/IGF-IR and p-AKT/AKT, but not p-ERK/ERK. In conclusion, the inhibition of cell viability by fucoidan in HT-29 cells may be due to the downregulation of IGF-IR signaling through the main IRS-1/PI3K/AKT pathway. Fucoidan also partially impacted Ras/Raf signaling in the Ras/Raf/ERK pathway. Therefore, we suggest that fucoidan may be a suitable candidate chemopreventive agent in HT-29 colon cancer cells.

Fucoidan has been reported to have abundant biological activities. The objective of the present study was to detect the protective effects of fucoidan…

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...

https://doi.org/10.18632/oncotarget.10016 Farzaneh Atashrazm, Ray M. Lowenthal, Joanne L. Dickinson, Adele F. Holloway, Gregory M. Woods

Fucoidans have been reported to exert anticancer effects with simultaneous low toxicity against healthy tissue. That correlation was observed in several cancer models, however, it has never been investigated in head and neck cancer before. To magnify the efficacy of conventional therapy, the adminis …

The inflammatory hypothesis is one of the most important mechanisms of depression. Fucoidan is a bioactive sulfated polysaccharide abundant in brown s…

Background Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities. Methodology/Principal Finding FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases. Conclusions/Significance These data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent.