The Potency of Seaweed Sulfated Polysaccharides for the Correction of Hemostasis Disorders in COVID-19.

Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.

Evaluation of the antidepressant- and anxiolytic-like effects of a hydrophilic extract from the green seaweed Ulva sp. in rats.

OBJECTIVES: The green seaweed Ulva sp. contains a large amount of ulvans, a family of sulphated polysaccharides. The present study was designed to investigate in rats the antidepressant- and anxiolytic-like effects of a hydrophilic extract of Ulva sp. (MSP) containing about 45% of ulvans. METHODS: After a 14-day administration of MSP at doses of 10, 20 and 40 mg/kg/day, 48 and 60 male adult Wistar rats were respectively tested in the elevated plus-maze (EPM) and the forced swimming test (FST). In the FST, MSP effects were compared to the reference antidepressant drug imipramine (IMI) (10 mg/kg/day). Acute and sub-chronic toxicities of the extract were also assessed in male and female rats following OECD guidelines. RESULTS: MSP treatment did not modify anxiety-related behaviour in the EPM. In contrast, MSP induced a dose-dependent reduction of immobility behaviour in the FST. At the highest tested dose of 40 mg/kg, MSP displayed a significant antidepressant-like effect similar to IMI. MSP did not modify the exploratory behaviour of rats in the open field test and did not produce any toxic effect. DISCUSSION: MSP may potentially represent a good adjunct or alternative to existing antidepressant therapeutics. Further studies are necessary to confirm the mechanism of action of MSP and its modulation of brain functioning.

Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

Marine Bioactive Compounds Derived from Macroalgae as New Potential Players in Drug Delivery Systems: A Review.

The marine algal ecosystem is characterized by a rich ecological biodiversity and can be considered as an unexploited resource for the discovery and isolation of novel bioactive compounds. In recent years, marine macroalgae have begun to be explored for their valuable composition in bioactive compounds and opportunity to obtain different nutraceuticals. In comparison with their terrestrial counterparts, Black Sea macroalgae are potentially good sources of bioactive compounds with specific and unique biological activities, insufficiently used. Macroalgae present in different marine environments contain several biologically active metabolites, including polysaccharides, oligosaccharides, polyunsaturated fatty acids, sterols, proteins polyphenols, carotenoids, vitamins, and minerals. As a result, they have received huge interest given their promising potentialities in supporting antitumoral, antimicrobial, anti-inflammatory, immunomodulatory, antiangiogenic, antidiabetic, and neuroprotective properties. An additional advantage of ulvans, fucoidans and carrageenans is the biocompatibility and limited or no toxicity. This therapeutic potential is a great natural treasure to be exploited for the development of novel drug delivery systems in both preventive and therapeutic approaches. This overview aims to provide an insight into current knowledge focused on specific bioactive compounds, which represent each class of macroalgae e.g., ulvans, fucoidans and carrageenans, respectively, as valuable potential players in the development of innovative drug delivery systems.

Seaweed polysaccharides and derived oligosaccharides stimulate defense responses and protection against pathogens in plants.

Plants interact with the environment by sensing "non-self" molecules called elicitors derived from pathogens or other sources. These molecules bind to specific receptors located in the plasma membrane and trigger defense responses leading to protection against pathogens. In particular, it has been shown that cell wall and storage polysaccharides from green, brown and red seaweeds (marine macroalgae) corresponding to ulvans, alginates, fucans, laminarin and carrageenans can trigger defense responses in plants enhancing protection against pathogens. In addition, oligosaccharides obtained by depolymerization of seaweed polysaccharides also induce protection against viral, fungal and bacterial infections in plants. In particular, most seaweed polysaccharides and derived oligosaccharides trigger an initial oxidative burst at local level and the activation of salicylic (SA), jasmonic acid (JA) and/or ethylene signaling pathways at systemic level. The activation of these signaling pathways leads to an increased expression of genes encoding: (i) Pathogenesis-Related (PR) proteins with antifungal and antibacterial activities; (ii) defense enzymes such as pheylalanine ammonia lyase (PAL) and lipoxygenase (LOX) which determine accumulation of phenylpropanoid compounds (PPCs) and oxylipins with antiviral, antifugal and antibacterial activities and iii) enzymes involved in synthesis of terpenes, terpenoids and/or alkaloids having antimicrobial activities. Thus, seaweed polysaccharides and their derived oligosaccharides induced the accumulation of proteins and compounds with antimicrobial activities that determine, at least in part, the enhanced protection against pathogens in plants.

Green seaweeds ulvan-cellulose scaffolds enhance in vitro cell growth and in vivo angiogenesis for skin tissue engineering.

Cellulose has been extracted from a wide range of land resources, whereas it has been scarcely exploited from marine resources. Cellulose from green seaweeds can be extracted together with smaller molecules called ulvans. We have successfully extracted and characterized cellulose from Ulva sp. Solid state 13C NMR indicated the presence of ulvans in the cellulose extracts. The extracted cellulose was blended with polylactide and polydioxanone and electrospun into nanofibrous mats with a range of physico-chemical properties. These cellulose-based scaffolds were assessed in vitro using fibroblast cells and showed accelerated cell growth. In vivo biocompatibility studies using a Wistar rat model indicated the absence of foreign body response and enhanced angiogenesis.

Effect of extraction procedures on the chemical structure, antitumor and anticoagulant properties of ulvan from Ulva lactuca of Tunisia coast.

The effect of extraction procedures on chemical composition, structural, antitumor and anticoagulant properties of the sulphated polysaccharide 'ulvan' from the green seaweed Ulva lactuca were investigated. The structural features of ulvans were carried out by FTIR and by one- and two- dimensional 1H and 13C NMR spectroscopic. The ulvans were mainly composed of rhamnose, xylose, and uronic acid. Chemical and spectroscopic analyses demonstrated that ulvans were constituted of (1→4)-ß-glucuronic acid, (1→3,4)-α-L-rhamnose-3-sulphate and (1→4)-α-xylose. The extraction procedures effect were observed in chemical structure, Mw and biological activities. Cytotoxic activity of enzymatic-chemical extract on cervical cancer cells (HeLa) (IC50 = 1000 µg/mL) was higher than on normal peripheral blood lymphocytes cells (PBL). Acid extracts promoted to reduce HeLa cells and to grow PBL cells. At high concentrations, acid extracts showed the highest APTT and TT clotting time. Antitumoral and anticoagulant activities of ulvans from Ulva lactuca promote their use as effective therapeutic agent.

Sulfated Polysaccharides from Marine Algae as a Basis of Modern Biotechnologies for Creating Wound Dressings: Current Achievements and Future Prospects.

Wound healing involves a complex cascade of cellular, molecular, and biochemical responses and signaling processes. It consists of successive interrelated phases, the duration of which depends on a multitude of factors. Wound treatment is a major healthcare issue that can be resolved by the development of effective and affordable wound dressings based on natural materials and biologically active substances. The proper use of modern wound dressings can significantly accelerate wound healing with minimum scar mark. Sulfated polysaccharides from seaweeds, with their unique structures and biological properties, as well as with a high potential to be used in various wound treatment methods, now undoubtedly play a major role in innovative biotechnologies of modern natural interactive dressings. These natural biopolymers are a novel and promising biologically active source for designing wound dressings based on alginates, fucoidans, carrageenans, and ulvans, which serve as active and effective therapeutic tools. The goal of this review is to summarize available information about the modern wound dressing technologies based on seaweed-derived polysaccharides, including those successfully implemented in commercial products, with a focus on promising and innovative designs. Future perspectives for the use of marine-derived biopolymers necessitate summarizing and analyzing results of numerous experiments and clinical trial data, developing a scientifically substantiated approach to wound treatment, and suggesting relevant practical recommendations.

Smart ulvan films responsive to stimuli of plasticizer and extraction condition in physico-chemical, optical, barrier and mechanical properties.

Smart films were produced with ulvan extracted from the green seaweed Ulva. lactuca at different extraction conditions, by varying the glycerol or sorbitol in specific plasticizer concentration. Chemical composition and molecular weight characteristics of ulvans were carried out by GLC and HPSEC analysis, respectively. Regardless of the extraction procedure, the investigation revealed that ulvans were selected as reproducible and suitable materials of stimuli-responsive due to its peculiar chemical composition and self-aggregation molecular behavior. When using the terminology of stimuli-responsive system, we declare that the physico-chemical, barrier, optical, and mechanical characteristics of ulvan films system are strongly responsive to extraction conditions and to plasticizer type and concentration. As plasticizer concentration increased, thickness, moisture content (MC), water solubility, water vapor permeability (WVP), transparency, elongation at break (EAB), usually UV and visible light protection of ulvan films increased, while, their tensile strength (TS) decreased significantly. The films prepared with glycerol exhibited better solubility, transparency and mechanical properties, than those with sorbitol. However, the films formed with sorbitol had the greatest moisture resistance and more effective vapor, visible and UV light barrier as well as the lowest solubility. The FTIR spectra evidenced the expected outcome of the chemical interaction and miscibility kind between polysaccharides and plasticizers.

Immunomodulating effect of a seaweed extract from Ulva armoricana in pig: Specific IgG and total IgA in colostrum, milk, and blood.

The transfer of passive immunity from sows to piglets can be improved through the administration of immuno-stimulating products before farrowing. This study evaluated the immuno-stimulating effect of an algal sulfated polysaccharide extract (MSP extract) from the green algae Ulva armoricana when administrated orally to sows at the end of gestation. Four diets were tested: Control (no MSP extract), MSP1 (2 g/day of MSP extract), MSP2 (8 g/day), and MSP3 (16 g/day). The experimental diets were provided in two periods: before the last atrophic rhinitis vaccine booster, and a week before farrowing. Anti-Bordetella IgG antibodies were recorded in blood, colostrum, and milk, and total IgA were measured in colostrum and milk. Titer kinetics between the blood sampled before farrowing and colostrum displayed an increase in specific IgG for MSP3. Moreover, the MSP2 diet increased the level of total IgA in milk compared to the control group. Although the immuno-stimulating effect of MSP extract on piglet performance was not concurrent across the different supplementation levels, the present study supports the use of natural algae extract (MSP) as an immunomodulating solution in swine production.

Ulvans induce resistance against plant pathogenic fungi independently of their sulfation degree.

The present work aimed to evaluate the defense responses induced by chemically sulfated ulvans in Arabidopsis thaliana plants against the phytopathogenic fungi Alternaria brassicicola and Colletotrichum higginsianum. Derivatives with growing sulfate content (from 20.9 to 36.6%) were prepared with SO3-pyridine complex in formamide. NMR and FTIR spectroscopic analyses confirmed the increase of sulfate groups after the chemical sulfation process. The native sulfated polysaccharide (18.9% of sulfate) and its chemically sulfated derivatives similarly reduced the severity of both pathogenic fungi infections. Collectively, our results suggest that ulvans induce resistance against both fungal pathogens independently of its sulfation degree.