•Fucoidan reduces systematic inflammation and attenuates MetS in HFD-fed mice.•Fucoidan increases Akkermansia population in the gut microbiota of mice with MetS.•Fucoidan ameliorates MetS in ...association with a robust modulation of gut microbiota.
Emerging evidence shows that dietary fucoidan contribute to the prevention and treatment of diverse diseases. Here, using a mouse model, we first demonstrate a similar beneficial effect of two fucoidans from Laminaria japonica and Ascophyllum nodosum on diet-induced metabolic syndrome (MetS). Both fucoidans were found to significantly reduce body weight, fasting blood glucose, hepatic steatosis and systematic inflammation. To decipher the mechanism behind this therapeutic effect, the gut microbiota was analyzed as fucoidan is poorly absorbed after oral administration. Interestingly, we found that benign microbes which conferred benefits upon host wellbeing including Akkermansia muciniphila and short-chain fatty acid-producers such as Alloprevotella, Blautia and Bacteroides were highly enriched by fucoidans. Collectively, our study illustrates a novel application of fucoidan as an anti-MetS functional food and, from a gut microbiota perspective, sheds new insight into the mechanism by which unabsorbed polysaccharide exerts a system therapeutic effect.
The cosmetics industry is one of the most profitable in the world today. This multi-billion-dollar industry has a profound sociological impact worldwide. Its influence is global, with most ...individuals being concerned with conserving their physical appearance, beauty, and youth. The consumers' desire for novel, better, and safer products has stimulated the utilization of natural-product-based cosmeceutical formulations over synthetic chemicals. With remarkable advancements in marine bioresource technology, algal polysaccharides have gained much attention as bioactive ingredients in cosmeceuticals. Algae biosynthesize a variety of polysaccharides including fucoidans, alginates, carrageenans, galactans, agar, porphyran, glucans, and ulvans, all of which exhibit distinctive structural and functional properties. Many of these materials have been proven to possess skin-protective effects, including anti-wrinkle, lightening, moisturizing, UV protective, antioxidative, and anti-inflammatory activity. Moreover, they have a wide spectrum of physicochemical properties, such as the ability to form hydrogels, which extend their utilization as emulsifiers, stabilizers, and viscosity controlling ingredients in cosmeceuticals. Accordingly, algal hydrocolloids and their synthetic derivatives can also be applied in tissue engineering and cosmetic surgery. The challenge is to increase awareness about these polysaccharides and consequently generate value-added products. This review discusses the beneficial biological and physicochemical properties of algal polysaccharides, highlighting their potential in cosmeceutical applications.
Effective thrombolysis is critical to rapidly rebuild blood flow for thrombosis patients. Drug delivery systems have been developed to address inadequate pharmacokinetics of thrombolytic agents, but ...challenges still remain in the timely removal of blood clots regarding the dense fibrin networks. Herein, rod-shaped tubular micromotors were developed to achieve efficient penetration and thorough destruction of thrombi. By using electrospun fiber fragments as the template, urokinase (uPA)-loaded polydopamine (PDA) microtubes with surface decorated fucoidan (FuPDAuPA) were prepared at the aspect ratio of around 2. One E. coli Nissle 1917 (EcN) was assembled into one microtube to construct a FuPDAuPA@EcN hybrid micromotor through PDA adhesion and L-aspartate induction. The pharmacokinetic analysis indicates that the encapsulation of uPA into micromotors extends the half-life from 0.4 to 5.6 h and increases the bioavailability over 10 times. EcN-propelled motion elevates adsorption capacities of FuPDAuPA@EcN for more than four times compared with that of FuPDAuPA. The fucoidan-mediated targeting causes 2-fold higher thrombolysis capacity in vitro and over 10-fold higher uPA accumulation in thrombi in vivo. In the treatment of venous thrombi at mouse hindlimbs, intravenous administration of FuPDAuPA@EcN completely removed blood clots with almost full recovery of blood flows and apparently alleviated tail bleeding. It should be noted that FuPDAuPA@EcN treatment at a reduced uPA dose caused no significant difference in the blood flow rate compared with those of FuPDAuPA. The synergistic action of fucoidan-induced targeting and EcN-driven motion provides a prerequisite for promoting thrombolytic efficacy and reducing uPA dose and bleeding side effect.
The standard treatment to thrombosis patient is intravenous infusion of thrombolytic agents, but the associated bleeding complications and impairment of normal haemostasis greatly offset the therapeutic benefits. Drug delivery systems have been developed to address the limitations of inadequate pharmacokinetics of thrombolytic agents, but challenges still exist in less efficient penetration into dense networks for thorough destruction of thrombi. Up to now only few attempts have been made to construct nano-/micromotors for combating thrombosis and there is no single case that antithrombosis is assisted by bacteria or cells-propelled motors. Herein, bacteria-propelled microtubes were developed to carry urokinase for efficient penetration into blood clots and effective thrombolysis. The synergistic action of bacteria-driven motion and specific ligand-induced targeting holds a promising treatment strategy for life-threatening cardiovascular diseases such as thrombosis and atherosclerosis.
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Fucoidans are a group of fucose-containing sulfated polysaccharides found in many species of brown seaweeds, with numerous bioactive properties. As a highly bioactive seaweed substance with many ...promising physiological activities, fucoidans have attracted attention from many industries all over the world. Even though fucoidans are a rich source of bioactive properties, the structural properties and bioactive mechanisms of fucoidans are poorly understood. Therefore, novel studies that either characterize the physical properties or biological activities of fucoidans will fill the knowledge gap between industrial applications and the scientific background of those applications. Both purified and partially purified fucoidans isolated from brown seaweeds present high potential as preventative and therapeutic agents against number of chronic diseases, due to their anti-inflammatory, antioxidant, anticancer, neuroprotective, antiviral, antimicrobial, and anticoagulative properties. This Special Issue is aimed at presenting updated information on well-documented studies of the structural characterization and major biological actions relevant for medical, cosmeceutical, and pharmaceutical applications that fucoidans isolated from brown seaweed can offer.
Platelet endothelial aggregation receptor 1 (PEAR1) is a single-transmembrane orphan receptor primarily expressed on platelets and endothelial cells. Genetic variants of PEAR1 have repeatedly and ...independently been identified to be associated with cardiovascular diseases, including coronary artery disease.
We have identified sulfated fucoidans and their mimetics as ligands for PEAR1 and proposed that its endogenous ligand is a sulfated proteoglycan. The aim of this study was to test this hypothesis.
A heparin proteoglycan-mimetic (HPGM) was created by linking unfractionated heparin (UFH) to albumin. The ability of the HPGM, UFH and selectively desulfated heparins to stimulate platelet aggregation and protein phosphorylation was investigated. Nanobodies against the 12th to 13th epidermal growth factor-like repeat of PEAR1 and phosphoinositide 3-kinase (PI3K) isoform-selective inhibitors were tested for the inhibition of platelet activation.
We show that HPGM, heparin conjugated to an albumin protein core, stimulates aggregation and phosphorylation of PEAR1 in washed platelets. Platelet aggregation was abolished by an anti-PEAR1 nanobody, Nb138. UFH stimulated platelet aggregation in washed platelets, but desulfated UFH did not. Furthermore, HPGM, but not UFH, stimulated maximal aggregation in platelet-rich plasma. However, both HPGM and UFH increased integrin αIIbβ3 activation in whole blood. By using PI3K isoform-selective inhibitors, we show that PEAR1 activates PI3Kβ, leading to Akt phosphorylation.
Our findings reveal that PEAR1 is a receptor for heparin and HPGM and that PI3Kβ is a key signaling molecule downstream of PEAR1 in platelets. These findings may have important implications for our understanding of the role of PEAR1 in cardiovascular disease.
•Variants of PEAR1 are associated with cardiovascular disease and increased platelet aggregability.•Unfractionated heparin and heparin proteoglycan-mimetics cause platelet activation via PEAR1.•Both agonists cause aggregation in washed platelets and αIIbβ3 activation in whole blood.•PEAR1 aggregation is mediated via PI3Kβ, a PI3K isoform known to induce platelet priming.
Resveratrol is a well-studied dietary polyphenol with diverse health-promoting bioactivities. However, the aqueous insolubility and chemical instability of resveratrol hamper its practical ...application. This study set out to address these limitations by constructing zein-fucoidan composite nanoparticles as a delivery system of resveratrol. The optimized resveratrol-loaded zein-fucoidan particles (RE-ZFP) were obtained at zein-to-fucoidan ratio of 2:1 (w/w) and zein-to-resveratrol ratio of 10:1 (w/w), and RE-ZFP showed evenly distributed and smoothly spherical microstructures, mean particle size of 121 nm, ζ-potential of − 41 mV, encapsulation efficiency for resveratrol of 95.4%. Electrostatic, steric, hydrophobic, and hydrogen-bonding interactions were major forces required to form RE-ZFP. In addition, RE-ZFP exhibited greater photostability and colloidal stability (including pH, ionic, and storage stabilities) than resveratrol-loaded zein particles (RE-ZP). Particularly, RE-ZFP showed fairly good pH stability. Moreover, zein-fucoidan-based delivery system exhibited a controlled release of resveratrol under in vitro digestion. Finally, zein-fucoidan nanocarriers presented extremely low cytotoxicity to HIEC-6 cells. All the findings demonstrate that the zein-fucoidan nanoparticles developed in the current work will be a prospective strategy for loading resveratrol and other hydrophobic bioactive ingredients and thus extending their application in nutraceuticals or pharmaceuticals.
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•Fucoidan can stabilize zein particles well at zein-to-fucoidan mass ratio of 2:1.•Zein-fucoidan nanoparticles can efficiently encapsulate and protect resveratrol.•Addition of fucoidan improved the colloidal stability of zein-based particles.•Zein-fucoidan nanoparticles manifested a controlled release of resveratrol.•Zein-fucoidan nanoparticles showed no cytotoxicity and biocompatibility.
Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical ...evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC) patients.
We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC). Sixty eligible patients with mCRC were included. Finally, 54 patients were enrolled, of whom 28 were included in the study group and 26 in the control group. The primary endpoint was the disease control rate (DCR), and secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and quality of life (QOL).
The DCRs were 92.8% and 69.2% in the study and control groups, respectively (
= 0.026), in a median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not significantly differ between the two groups.
This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with mCRC. The results indicate that LMF combined with chemotarget agents significantly improved the DCR.
The surface of rocky mineral talc has good floatability, and separating it from valuable sulfide minerals by flotation is challenging. Here, in the xanthate system for talc, the depression effect and ...mechanism of a novel depressant CF were investigated. In the system where CF was used as a depressant and xanthate as a collector, CF adsorbed on the talc surface and reduced the hydrophobicity of the surface, thus effectively reducing the floatability of talc in flotation. Moreover, the xanthate hardly adsorbed on the talc surface and did not affect the adsorption of CF, as shown by FTIR and adsorption tests. The absorption energy of CF on the surface of talc was found to be negative by DFT calculations and was physical adsorption by hydrogen bonding, and the XPS analysis also confirmed that there was no chemisorption. This finding has theoretical and practical significance for the research of talc separation.
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Injection of recombinant tissue plasminogen activator (rt-PA) is the standard drug treatment for thrombolysis. However, rt-PA shows risk of hemorrhages and limited efficiency even at high doses. ...Polysaccharide-poly(isobutylcyanoacrylate) nanoparticles functionalized with fucoidan and loaded with rt-PA were designed to accumulate on the thrombus. Fucoidan has a nanomolar affinity for the P-selectin expressed by activated platelets in the thrombus. Solid spherical fluorescent nanoparticles with a hydrodynamic diameter of 136 ± 4 nm were synthesized by redox radical emulsion polymerization. The clinical rt-PA formulation was successfully loaded by adsorption on aminated nanoparticles and able to be released in vitro. We validated the in vitro fibrinolytic activity and binding under flow to both recombinant P-selectin and activated platelet aggregates. The thrombolysis efficiency was demonstrated in a mouse model of venous thrombosis by monitoring the platelet density with intravital microscopy. This study supports the hypothesis that fucoidan-nanoparticles improve the rt-PA efficiency. This work establishes the proof-of-concept of fucoidan-based carriers for targeted thrombolysis.
Core-shell polymer nanoparticles are functionalized with fucoidan to target P-selectin and promote the specific accumulation of loaded rt-PA at the thrombus. Display omitted
Inflammation is the initial response of the immune system to potentially harmful stimuli (e.g., injury, stress, and infections). The process involves activation of macrophages and neutrophils, which ...produce mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory and anti-inflammatory cytokines. The pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) are considered as biomarkers of inflammation. Even though it occurs as a physiological defense mechanism, its involvement in the pathogenesis of various diseases is reported. Rheumatoid arthritis, inflammatory bowel disease, Alzheimer’s disease, and cardiovascular diseases are only a part of the diseases, in which pathogenesis the chronic inflammation is involved. Fucoidans are complex polysaccharides from brown seaweeds and some marine invertebrates, composed mainly of l-fucose and sulfate ester groups and minor amounts of neutral monosaccharides and uronic acids. Algae-derived fucoidans are studied intensively during the last years regarding their multiple biological activities and possible therapeutic potential. However, the source, species, molecular weight, composition, and structure of the polysaccharides, as well as the route of administration of fucoidans, could be crucial for their effects. Fucoidan is reported to act on different stages of the inflammatory process: (i) blocking of lymphocyte adhesion and invasion, (ii) inhibition of multiple enzymes, and (iii) induction of apoptosis. In this review, we focused on the immunemodulating and anti-inflammatory effects of fucoidans derived from macroalgae and the models used for their evaluation. Additional insights on the molecular structure of the compound are included.
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