2016

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.

Glucosamine is an essential substrate for N-linked protein glycosylation. However, elevated levels of glucosamine can induce endoplasmic reticulum (ER) stress. Glucosamine-induced ER stress has bee...

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.

Glucosamine is an essential substrate for N-linked protein glycosylation. However, elevated levels of glucosamine can induce endoplasmic reticulum (ER) stress. Glucosamine-induced ER stress has bee...

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.

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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…

There may be good reason to take glucosamine supplements for symptoms other than joint problems.

Glucosamine (GlcN), a dietary supplement widely utilized to promote joint health and effective in the treatment of osteoarthritis, is an effective macroautophagy/autophagy activator in vitro and in vivo. Previous studies have shown that autophagy is required for hepatitis B virus (HBV) …

Osteoarthritis (OA) is one of the major joint diseases, and the synovial inflammation is involved in the pathogenesis and progression of OA. Glucosamine (GlcN) is widely used as a dietary supplement for OA, and is expected to exert the antiinflammatory action in OA. However, the detailed mechanism for the antiinflammatory action of GlcN remains poorly understood. In this study, to elucidate the molecular mechanism involved in the GlcN-medicated regulation of synovial cell activation, we comprehensively analyzed the effect of GlcN on the gene expression using a human synovial cell line MH7A by DNA microarray. The results indicated that GlcN significantly downregulates the expression of 187 genes (≤1/1.5-fold) and upregulates the expression of 194 genes (≥1.5-fold) in IL-1β-stimulated MH7A cells. Interestingly, pathway analysis indicated that among the 10 pathways into which the GlcN-regulated genes are categorized, the 4 pathways are immune-related. Furthermore, GlcN suppressed the expression of proinflammatory cytokine genes (such as IL-6, IL-8, IL-24 and TNF-α genes). In addition, GlcN-mediated O-GlcNAc modification was involved in the downregulation of TNF-α and IL-8 genes but not IL-6 and IL-24 genes, based on the effects of alloxan, an O-GlcNAc transferase inhibitor. Thus, GlcN likely exerts an antiinflammatroy action in OA by suppressing the expression of proinflammatory cytokine genes in synovial MH7A cells by O-GlcNAc modification-dependent and -independent mechanisms.

Plantar fasciitis is the most common cause of the plantar heel pain. Its main features are a pain, tenderness mostly on the medial aspect of the calcaneum near the sole of heel. There are many conservative methods for treatment of the lantar fasciitis which include rest, massage, night splints, orthoses, injections, cast NSAID, shock wave therapy. The glucosamine is one of the nutritional product which has a good anti- properties and is already in use for arthritis knee. Depending on anti-inflammatory analgesic property can also be used in planter fasciitis. In this study 17 patients were studied after giving fixed dose of 1200 mg of glucosamine. The evaluation was done on linkert pain score. The p-value in studied group was

Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects. Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post‑translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs. Glucosamine acts as an anticancer agent possibly by inhibiting N‑linked glycosylation. The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling. Human aldehyde dehydrogenase‑positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer‑binding transcription factor 4 (OCT‑4), and Krüppel‑like factor 4 (KLF4)] expression was determined using the reverse transcription‑quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis. Furthermore, the number of mammosphere‑forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined. It was determined that glucosamine treatment decreased the viability of ALDH+ breast CSCs. Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT‑4 and KLF4 expression level, and a decreased number of MFUs. This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.

I read with interest the paper by Li et al 1 reporting the association of regular glucosamine use with lower mortality. The authors report significantly lower all-cause mortality HR 0.85 (95% CI 0.82 to 0.89), cardiovascular mortality HR 0.82 (95% CI 0.74 to 0.90), cancer mortality HR 0.94 (95% CI 0.88 to 0.99), respiratory mortality HR 0.73 (95% CI 0.66 to 0.81) and digestive mortality HR 0.74 (95% CI 0.62 to 0.90). The magnitude of the reported reduction in mortality is striking, as is the consistency across major disease categories. The results reported by the authors are consistent with other prior epidemiological studies looking at glucosamine and mortality.2–4 The biological plausibility for glucosamine having such pronounced causative effects …

Background: Glucosamine hydrochloride (GlcN·HCl) has been shown to inhibit cell growth and matrix synthesis, but not with N-acetyl-glucosamine (GlcNAc) supplementation. This effect might be related to an inhibition of critical growth factors (GF), or to a different metabolization of the two glucosamine derivatives. The aim of the present study was to evaluate the synergy between GlcN·HCl, GlcNAc, and GF on proliferation and cartilage matrix synthesis. Method: Bovine chondrocytes were cultivated in monolayers for 48 h and in three-dimensional (3D) chitosan scaffolds for 30 days in perfusion bioreactors. Serum-free (SF) medium was supplemented with either growth factors (GF) TGF-β (5 ng mL−1) and IGF-I (10 ng mL−1), GlcN·HCl or GlcNAc at 1mM each or both. Six groups were compared according to medium supplementation: (a) SF control; (b) SF + GlcN·HCl; (c) SF + GlcNAc; (d) SF + GF; (e) SF + GF + GlcN·HCl; and (f) SF + GF + GlcNAc. Cell proliferation, proteoglycan, collagen I (COL1), and collagen II (COL2) synthesis were evaluated. Results: The two glucosamines showed opposite effects in monolayer culture: GlcN·HCl significantly reduced proliferation and GlcNAc significantly augmented cellular metabolism. In the 30 days 3D culture, the GlcN·HCl added to GF stimulated cell proliferation more than when compared to GF only, but the proteoglycan synthesis was smaller than GF. However, GlcNAc added to GF improved the cell proliferation and proteoglycan synthesis more than when compared to GF and GF/GlcN·HCl. The synthesis of COL1 and COL2 was observed in all groups containing GF. Conclusion: GlcN·HCl and GlcNAc increased cell growth and stimulated COL2 synthesis in long-time 3D culture. However, only GlcNAc added to GF improved proteoglycan synthesis.

An in-depth scientific review of glucosamine and chondroitin - including their background, evidenced-based health benefits, risks, side effects and more!

In Alzheimer’s disease (AD), amyloid-β (Aβ) oligomers are considered key mediators of synaptic dysfunction and cognitive impairment. These unstable intermediate Aβ species can interfere with different cellular organelles, leading to neuronal cell death, through the formation of Ca2+-permeable membrane pores, impairment in the levels of acetylcholine neurotransmitters, increased insulin resistance, promotion of pro-inflammatory cascades, among others. Based on a series of evidences that indicate the key role of glycosaminoglycans (GAGs) in amyloid plaque formation, we evaluated the capacity of four monosaccharides, i.e., glucosamine (GlcN), N-acetyl glucosamine (GlcNAc), glucosamine-6-sulfate (GlcN6S), and glucosamine-6-phosphate (GlcN6P), to reduce the Aβ-mediated pathological hallmarks. The tested monosaccharides, in particular, GlcN6S and GlcN6P, were able to interact with Aβ aggregates, reducing neuronal cell death, Aβ-mediated damage to the cellular membrane, acetylcholinesterase activity, insulin resistance, and pro-inflammation levels.

Glucosamine hydrochloride (GH) and chondroitin sulfate (CS) are commonly used for the treatment of osteoarthritis (OA). The aim of this study was to assess their effects, alone and in combination, on preventing aggrecan degradation and inflammation in ...

What is glucosamine? Glucosamine is a polysaccharide that naturally occurs in cartilaginous joint tissues and is involved in protein and lipid synthesis. […]