Glyconutrients

Fucus vesiculosus L., known as bladderwrack, belongs to the brown seaweeds, which are widely distributed throughout northern Russia, Atlantic shores of Europe, the Baltic Sea, Greenland, the Azores, the Canary Islands, and shores of the Pacific Ocean. Fucoidan is a major fucose-rich sulfated polysaccharide found in Fucus (F.) vesiculosus. The pharmacokinetic profiling of active compounds is essential for drug development and approval. The aim of the study was to evaluate the pharmacokinetics and tissue distribution of fucoidan in rats after a single-dose oral administration. Fucoidan was isolated from F. vesiculosus. The method of measuring anti-activated factor X (anti-Xa) activity by amidolytic assay was used to analyze the plasma and tissue concentrations of fucoidan. The tissue distribution of fucoidan after intragastric administration to the rats was characterized, and it exhibited considerable heterogeneity. Fucoidan preferentially accumulates in the kidneys (AUC0–t = 10.74 µg·h/g; Cmax = 1.23 µg/g after 5 h), spleen (AUC0–t = 6.89 µg·h/g; Cmax = 0.78 µg/g after 3 h), and liver (AUC0–t = 3.26 µg·h/g; Cmax = 0.53 µg/g after 2 h) and shows a relatively long absorption time and extended circulation in the blood, with a mean residence time (MRT) = 6.79 h. The outcome of this study provides additional scientific data for traditional use of fucoidan-containing plants and offers tangible support for the continued development of new effective pharmaceuticals using fucoidan.

Increased interest in natural antioxidants has brought to light the fucoidans (sulfated polysaccharides present in brown marine algae) as highly valued nutrients as well as effective and safe therapeutics against several diseases. Based on their satisfactory in vitro antioxidant potency, researchers have identified this molecule as an efficient remedy for neuropathological as well as metabolic disorders. Some of this therapeutic activity is accomplished by upregulation of cytoprotective molecular pathways capable of restoring the enzymatic antioxidant activity and normal mitochondrial functions. Sirtuin-3 has been discovered as a key player for achieving the neuroprotective role of fucoidan by managing these pathways, whose ultimate goal is retrieving the entirety of the antioxidant response and preventing apoptosis of neurons, thereby averting neurodegeneration and brain injuries. Another pathway whereby fucoidan exerts neuroprotective capabilities is by interactions with P-selectin on endothelial cells, thereby preventing macrophages from entering the brain proper. Furthermore, beneficial influences of fucoidan have been established in hepatocytes after xenobiotic induced liver injury by decreasing transaminase leakage and autophagy as well as obtaining optimal levels of intracellular fiber, which ultimately prevents fibrosis. The hepatoprotective role of this marine polysaccharide also includes a sirtuin, namely sirtuin-1 overexpression, which alleviates obesity and insulin resistance through suppression of hyperglycemia, reducing inflammation and stimulation of enzymatic antioxidant response. While fucoidan is very effective in animal models for brain injury and neuronal degeneration, in general, it is accepted that fucoidan shows somewhat limited potency in liver. Thus far, it has been used in large doses for treatment of acute liver injuries. Thus, it appears that further optimization of fucoidan derivatives may establish enhanced versatility for treatments of various disorders, in addition to brain injury and disease.

This work aims to explore the amelioration of fucoidan on adenine-induced hyperuricemia and hepatorental damage. Adenine-induced hyperuricemic mice were administered with fucoidan, allopurinol and vehicle control respectively to compare the effects of the drugs. Serum uric acid, urea nitrogen, hepatorenal functions, activities of hepatic adenosine deaminase (ADA), xanthine oxidase (XOD), renal urate transporter 1 (URAT1) and NF-κB p65 were assessed. As the serum uric acid, urea nitrogen, creatinine, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) data demonstrated, the adenine not only mediated hepatorenal function disorders, but also induced hyperuricemia in mice. Meanwhile, activities of hepatic ADA and XOD were markedly augmented by adenine, and the expression of URAT1 was promoted, which was conducive to the reabsorption of urate. However, exposure to fucoidan completely reversed those adenine-induced negative alternations in mice, and the activities of hepatic ADA and XOD were recovered to the normal level. It was obvious that hepatic and renal functions were protected by fucoidan treatment. The expression of URAT1 was returned to normal, resulting in an increase of renal urate excretion and consequent healing of adenine-induced hyperuricemia in mice. Expression and activation of NF-κB p65 was promoted in kidneys of adenine treated mice, but suppressed in kidneys of mice exposed to fucoidan from Laminaria japonica or allopurinol. In conclusion, the fucoidan is a potential therapeutic agent for the treatment of hyperuricemia through dual regulatory roles on inhibition of hepatic metabolism and promotion of renal excretion of urate.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease which contributes to memory loss and cognitive decline in the elderly. Fucoidan, extracted from brown algae, is a complex sulfated polysaccharide and potential bioactive compound. In this study, we investigated whether fucoidan protects PC12 cells from apoptosis induced by a combination of beta-amyloid 25–35 (Aβ25–35) and d-galactose (d-Gal), and improves learning and memory impairment in AD model mice. The results indicated that fucoidan could inhibit the release of cytochrome c from the mitochondria to cytosol and activation of caspases, and increase the expression of apoptosis inhibitor proteins (IAPs), including livin and X-linked IAP (XIAP) in PC12 cells damaged by Aβ25–35 and d-Gal-induction. Fucoidan reversed the decreased activity of acetylcholine (ACh) and choline acetyl transferase (ChAT), as well as the increased activity of acetylcholine esterase (AChE), in AD model mice induced by infusion of d-Gal. Furthermore, fucoidan improved antioxidant activity in vitro and in vivo by activation of superoxide dismutase (SOD) and glutathione (GSH). These results suggested that fucoidan could protect PC12 cells from apoptosis and ameliorate the learning and memory impairment in AD model mice, which appeared to be due to regulating the cholinergic system, reducing oxidative stress, and inhibiting the caspase-dependent apoptosis pathway.

Several types of cancers share cellular and molecular behaviors. Although many chemotherapy drugs have been designed to weaken the defenses of cancer cells, these drugs may also have cytotoxic effects on healthy tissues. Fucoidan, a sulfated fucose-based polysaccharide from brown algae, has gained much attention as an antitumor drug owing to its anticancer effects against multiple cancer types. Among the anticancer mechanisms of fucoidan are cell cycle arrest, apoptosis evocation, and stimulation of cytotoxic natural killer cells and macrophages. Fucoidan also protects against toxicity associated with chemotherapeutic drugs and radiation-induced damage. The synergistic effect of fucoidan with existing anticancer drugs has prompted researchers to explore its therapeutic potential. This review compiles the mechanisms through which fucoidan slows tumor growth, kills cancer cells, and interacts with cancer chemotherapy drugs. The obstacles involved in developing fucoidan as an anticancer agent are also discussed in this review.

For a long time, fucoidan has been well known for its pharmacological activities, and recently low molecular weight fucoidan (LMF) has been used in food supplements and pharmaceutical products. In the present study, LMF was extracted from Laminaria japonica by enzyme hydrolysis. The toxicity of LMF in mouse and rat models was determined by many methods, such as total arsenic content, bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus assay. The present findings showed that LMF at 5000 μg/mL exhibited no mutagenicity. It also produced no formatting disruption of red blood cells in vivo. At 2000 mg/kg BW/day there were no toxicological indications. LMF is expected to be used as a safe food supplement.

Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline (0.4 mg kg−1) and human umbilical vein endothelial cells were cultured. vWF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce vWF level in vascular endothelial injury rats and also significantly reduce vWF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and vWF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

In this study, fucoidans with different molecular weight that were isolated from the brown alga Undaria pinnatifida (Phaeophyceae, Laminariales) were investigated for their ability to inhibit melanogenesis and scavenge superoxide and hydroxyl radicals. Fucoidan samples with low molecular weights of 89, 35, 17, and 6 kDa were prepared by radiation-degradation of a 378 kDa fucoidan isolated from U. pinnatifida. The inhibitory activity of fucoidan against melanin biosynthesis in B16BL6 melanoma cells was enhanced for low molecular weight samples. To investigate the increase in melanogenesis inhibition exhibited by the low molecular weight fucoidan, tyrosinase inhibition activity and radical scavenging activities were measured. There was an increase in the tyrosinase inhibition activity for low molecular weight samples. Additionally, the radical scavenging activity was increased for lower molecular weight fucoidans. These results suggest that low molecular weight fucoidans from seaweeds may have beneficial biological properties.

In this study, fucoidans with different molecular weight that were isolated from the brown alga Undaria pinnatifida (Phaeophyceae, Laminariales) were investigated for their ability to inhibit melanogenesis and scavenge superoxide and hydroxyl radicals. Fucoidan samples with low molecular weights of 89, 35, 17, and 6 kDa were prepared by radiation-degradation of a 378 kDa fucoidan isolated from U. pinnatifida. The inhibitory activity of fucoidan against melanin biosynthesis in B16BL6 melanoma cells was enhanced for low molecular weight samples. To investigate the increase in melanogenesis inhibition exhibited by the low molecular weight fucoidan, tyrosinase inhibition activity and radical scavenging activities were measured. There was an increase in the tyrosinase inhibition activity for low molecular weight samples. Additionally, the radical scavenging activity was increased for lower molecular weight fucoidans. These results suggest that low molecular weight fucoidans from seaweeds may have beneficial biological properties.

The intestinal microecology is an extremely complex ecosystem consisting of gut microbiota, intestinal mucosa and the intestinal immune system. The intestinal microecology performs several important ...

Fucoidan-a marine natural active polysaccharide derived from brown algae with a variety of medicinal activities and low toxicity-has been used as clinical drug for renal diseases for nearly 20 years. The pharmacological mechanism of fucoidan has been well-investigated, based on target molecules and …

Polymeric nanoparticles based on fucoidan and chitosan were developed to deliver quercetin as a novel functional food. Through the polyelectrolyte self-assembly method, fucoidan/chitosan (F/C) nanoparticles were obtained with three different weight ratios (1/1, 3/1, and 5/1). The content of quercetin in the fucoidan/chitosan nanoparticles was in the range 110 ± 3 to 335 ± 4 mg·mL−1, with the increase of weight ratio of fucoidan to chitosan in the nanoparticle. Physicochemically stable nanoparticles were obtained with a particle size within the 300–400 nm range and surface potential higher than +30 mV for the 1F/1C ratio nanoparticle and around −30 mV for the 3F/1C and 5F/1C ratios nanoparticles. The 1F/1C ratio nanoparticle became larger and more unstable as the pH increased from 2.5 to 7.4, while the 3F/1C and 5F/1C nanoparticles retained their initial characteristics. This result indicates that the latter nanoparticles were stable along the gastrointestinal tract. The quercetin-loaded fucoidan/chitosan nanoparticles showed strong antioxidant activity and controlled release under simulated gastrointestinal environments (in particular for the 3F/1C and 5F/1C ratios), preventing quercetin degradation and increasing its oral bioavailability.

Seaweeds have received huge interest in recent years given their promising potentialities. Their antioxidant, anti-inflammatory, antitumor, hypolipemic, and anticoagulant effects are among the most renowned and studied bioactivities so far, and these effects have been increasingly associated with their content and richness in both primary and secondary metabolites. Although primary metabolites have a pivotal importance such as their content in polysaccharides (fucoidans, agars, carragenans, ulvans, alginates, and laminarin), recent data have shown that the content in some secondary metabolites largely determines the effective bioactive potential of seaweeds. Among these secondary metabolites, phenolic compounds feature prominently. The present review provides the most remarkable insights into seaweed research, specifically addressing its chemical composition, phytopharmacology, and cosmetic applications.

Fucoidan is one of the dominant sulfated polysaccharide which was extracted from the brown seaweed Turbinaria decurrens. In the behavioral study mice …

Fucoidan is a marine polymer extracted from diverse types of brown algae. This polysaccharide showed great potential towards treatment of different ty…

Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated with LF or HF extracts were used for the in vitro model, and muscle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were used for the in vivo model. Although both the LF and HF extracts significantly inhibited α-glucosidase activity in a dose-dependent manner, the HF extract had a superior α-glucosidase inhibition than the LF extract. In addition, glucose uptake was significantly increased by LJ- and HF-treated groups when compared to the control group. Phosphorylation of protein kinase B and AMP-activated protein kinase was induced by LJ and HF in both the vivo and in vitro skeletal muscle models. Furthermore, LJ and HF significantly decreased tumor necrosis factor-α whereas both extracts increased interleukin (IL)-6 and IL-10 production in lipopolysaccharide-stimulated C2C12 myotubes. Taken together, these findings imply that the brown seaweeds LJ and HF could be useful therapeutic agents to attenuate muscle insulin resistance due to diet-induced obesity and its associated inflammation.

Fucoidan extracted from brown algae has multiple beneficial functions. In this study, we investigated the effects of low-molecular-weight fucoidan (oligo-FO) on renal fibrosis under in vitro and in vivo diabetic conditions, and its molecular mechanisms. Advanced glycation product (AGE)-stimulated rat renal proximal tubular epithelial cells (NRK-52E) and diabetic mice induced by high-fat diet and intraperitoneal injection of streptozotocin and nicotinamide were used. Oligo-FO treatment significantly inhibited anti-high mobility group box 1 (HMGB1)/RAGE/ anti-nuclear factor-kappa B (NF-κB)/transforming growth factor-β1 (TGF-β1)/TGF-β1R/Smad 2/3/fibronectin signaling pathway and HIF-1α activation in AGE-stimulated NRK-52E cells. Conversely, the expression and activity of Sirt-1; the levels of ubiquitin-specific peptidase 22 (USP22), p-AMPK, glucagon-like peptide-1 receptor (GLP-1R), and heme oxygenase-1 (HO-1); and Nrf2 activation were remarkably increased by oligo-FO in AGE-stimulated cells. However, the above effects of oligo-FO were greatly diminished by inhibiting Sirt-1, HO-1, or GLP-1R activity. Similar changes of these pro-fibrotic genes in the kidney and a marked attenuation of renal injury and dysfunction were observed in oligo-FO-treated diabetic mice. These findings indicated that the inhibitory effects of the oligo-FO on diabetes-evoked renal fibrosis are mediated by suppressing TGF-β1-activated pro-fibrogenic processes via Sirt-1, HO-1, and GLP-1R dependence. Collectively, fucoidan-containing foods or supplements may be potential agents for ameliorating renal diseases due to excessive fibrosis.

The aim of this study was to determine whether low-molecular-weight fucoidan (LMWF) can reduce TGF-β-mediated pathogenesis of tubulointerstitial fibro…

Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan ...

Tubulointerstitial fibrosis is recognized as a key determinant of progressive chronic kidney disease (CKD). Fucoidan, a sulphated polysaccharide extracted from brown seaweed, exerts beneficial effects in some nephropathy models. The present study evaluated the inhibitory effect of oligo-fucoidan (800 Da) on renal tubulointerstitial fibrosis. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Six weeks after the surgery, we fed the CKD mice oligo-fucoidan at 10, 20, and 100 mg/kg/d for 6 weeks and found that the oligo-fucoidan doses less than 100 mg/kg/d improved renal function and reduced renal tubulointerstitial fibrosis in CKD mice. Oligo-fucoidan also inhibited pressure-induced fibrotic responses and the expression of CD44, β-catenin, and TGF-β in rat renal tubular cells (NRK-52E). CD44 knockdown downregulated the expression of β-catenin and TGF-β in pressure-treated cells. Additional ligands for CD44 reduced the anti-fibrotic effect of oligo-fucoidan in NRK-52E cells. These data suggest that oligo-fucoidan at the particular dose prevents renal tubulointerstitial fibrosis in a CKD model. The anti-fibrotic effect of oligo-fucoidan may result from interfering with the interaction between CD44 and its extracellular ligands.

Tubulointerstitial fibrosis is recognized as a key determinant of progressive chronic kidney disease (CKD). Fucoidan, a sulphated polysaccharide extracted from brown seaweed, exerts beneficial effects in some nephropathy models. The present study evaluated the inhibitory effect of oligo-fucoidan (800 Da) on renal tubulointerstitial fibrosis. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Six weeks after the surgery, we fed the CKD mice oligo-fucoidan at 10, 20, and 100 mg/kg/d for 6 weeks and found that the oligo-fucoidan doses less than 100 mg/kg/d improved renal function and reduced renal tubulointerstitial fibrosis in CKD mice. Oligo-fucoidan also inhibited pressure-induced fibrotic responses and the expression of CD44, β-catenin, and TGF-β in rat renal tubular cells (NRK-52E). CD44 knockdown downregulated the expression of β-catenin and TGF-β in pressure-treated cells. Additional ligands for CD44 reduced the anti-fibrotic effect of oligo-fucoidan in NRK-52E cells. These data suggest that oligo-fucoidan at the particular dose prevents renal tubulointerstitial fibrosis in a CKD model. The anti-fibrotic effect of oligo-fucoidan may result from interfering with the interaction between CD44 and its extracellular ligands.

The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated prote …

Laminaria japonica is widely cultivated in East Asia, including South Korea. Fucoidan, a main component of L. japonica, protects neurons from neurological disorders such as ischemia and traumatic brain injury. In the present study, we examined the effects of extract from fermented L. japonica on the reduction of proliferating cells and neuroblasts in mice that were physically (with electric food shock) or psychologically (with visual, auditory and olfactory sensation) stressed with the help of a communication box. Vehicle (distilled water) or fermented L. japonica extract (50 mg/kg) were orally administered to the mice once a day for 21 days. On the 19th day of the treatment, physical and psychological stress was induced by foot shock using a communication box and thereafter for three days. Plasma corticosterone levels were significantly increased after exposure to physical stress and decreased Ki67 positive proliferating cells and doublecortin immunoreactive neuroblasts. In addition, western blot analysis demonstrated that physical stress as well as psychological stress decreased the expression levels of brain-derived neurotrophic factor (BDNF) and the number of phosphorylated cAMP response element binding protein (pCREB) positive nuclei in the dentate gyrus. Fermentation of L. japonica extract significantly increased the contents of reduced sugar and phenolic compounds. Supplementation with fermented L. japonica extract significantly ameliorated the increases of plasma corticosterone revels and decline in the proliferating cells, neuroblasts, and expression of BDNF and pCREB in the physically stressed mice. These results indicate that fermented L. japonica extract has positive effects in ameliorating the physical stress induced reduction in neurogenesis by modulating BDNF and pCREB expression in the dentate gyrus.

Polysaccharides from Laminaria japonica (LJPs) are reported to have various functional properties, but the effects and mechanisms of LJPs on obesity and its related diseases are unclear. This study demonstrated that LJPs prevented diet-induced obesity in a mice model, and improved obesity-related pa …

Polysaccharides from Laminaria japonica (LJPs) are reported to have various functional properties, but the effects and mechanisms of LJPs on obesity a…

Laminaria japonica, one of the most widespread seafood consumed in China and many other nations, has been traditionally utilized as an effective therapeutically active substance for treating weight loss, phlegm elimination, and detumescence for more than 2000 years. Numerous studies have found that

Laminaria japonica polysaccharides (LP) improved serum biochemical index, body weight index, and glucose tolerance in gestational diabetes mellitus (GDM) mice. This beneficial effects of LP could be ...

PET imaging using 68Ga-Fucoidan represents a valuable tool for assessing p-selectin activation in vivo discriminating ischemic stroke early after stroke onset.

Bladder cancer (BC) is a common urological cancer, with poor prognosis for advanced/metastatic stages. Various intensive treatments, including radical cystectomy, chemotherapy, immune therapy, and radiotherapy are commonly used for these patients. However, these treatments often cause complications …