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Protein reactivity of kappa-CGN and casein. Figure used with permission from Blakemore et al. (2014a).
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Carrageenan (CGN) is a common food additive that has been widely used for decades as a gelling, thickening and stabilizing agent. Carrageenan has been proven safe for human consumption; however, there has been significant confusion in the literature between CGN and the products of intentional acid-hydrolysis of CGN, which are degraded CGN (d-CGN) a...
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Introduction : Evaluation of anti-inflammatory action of Codelac ® Broncho with Thymus Serpyllum (elixir) in comparison with Fenspiride was carried out on the model of acute carrageenan inflammation of the paws in rats.
Materials and methods : Edema was caused by subplantar injection of 0.1 ml of 1% λ- carrageenan gel into the hind paw. The severit...
Citations
... They differ in their ability to gel and their solubility in water [61]. The κ form forms strong, stiff gels with potassium salts [57,62] and brittle gels with calcium salts [57], the ι form forms flexible gels with calcium salts, while carrageenan λ has no gelling ability [62] but can be used as a thickening agent [57,62]. In addition, the gel of ι carrageenan is transparent, in contrast to κ carrageenan [57]. ...
... They differ in their ability to gel and their solubility in water [61]. The κ form forms strong, stiff gels with potassium salts [57,62] and brittle gels with calcium salts [57], the ι form forms flexible gels with calcium salts, while carrageenan λ has no gelling ability [62] but can be used as a thickening agent [57,62]. In addition, the gel of ι carrageenan is transparent, in contrast to κ carrageenan [57]. ...
... Poligeenan has a low molecular weight, i.e., 10,000-20,000 Da, degraded carrageenan an average of 20,000-40,000 Da, while the carrageenan used in food products has a high molecular weight (200,000-800,000 Da). As suggested by the authors of the above review, confusing nomenclature causes problems in the precise understanding of studies [62] which was also noted during the writing of this paper. It is necessary to pay particular attention to the nomenclature and to distinguish between carrageenan found in food products and degraded carrageenan and poligeenan. ...
While the exact pathogenesis of IBD remains unclear, genetic, environmental and nutritional factors as well as the composition of the gut microbiome play crucial roles. Food additives, which are increasingly consumed in the Western diet, are being investigated for their potential effects on IBD. These additives can affect gut health by altering the composition of the microbiota, immune responses, and intestinal permeability, contributing to autoimmune diseases and inflammation. Despite the growing number of studies on food additives and IBD, the specific effects of carrageenan have not yet been sufficiently researched. This review addresses this gap by critically analyzing recent studies on the effects of carrageenan on the gut microbiota, intestinal permeability, and inflammatory processes. We searched the MEDLINE and SCOPUS databases using the following terms: carrageenan, carrageenan and inflammatory bowel disease, carrageenan and cancer, food additives and microbiome, food additives and intestinal permeability, and food additives and autoimmune diseases. In animal studies, degraded carrageenan has been shown to trigger intestinal ulceration and inflammation, highlighting its potential risk for exacerbating IBD. It can affect the gut microbiota, reduce bacterial diversity, and increase intestinal permeability, contributing to “leaky gut” syndrome. Some studies suggest that carrageenan may inhibit the growth of cancer cells by influencing the progression of the cell cycle, but the anti-cancer effect is still unclear. Carrageenan may also increase glucose intolerance and insulin resistance. Further research is needed to determine whether carrageenan should be excluded from the diet of individuals with IBD.
... For example, all representatives inhibit Haemophilus influenzae, Streptococcus oralis inhibits Streptococcus pneumoniae and Streptococcus sanguis inhibits Streptococcus pyogenes. The antiviral effect of carrageenans is most likely based on reduced attachment and entry of the virus into target cells, which reduces the viral load in the nose and nasopharynx and supports the protective function of the microbiota [94,95]. The barrier function of the microbiota plays an important role in protecting us from infections. ...
Emerging or re-emerging viral infections significantly affect human health. In recent decades, we have observed the emergence of new diseases in different geographical areas caused by a large number of highly pathogenic viruses belonging to the families Filoviridae, Arenaviridae, Bunyaviridae, Paramyxoviridae, Coronaviridae, Flaviviridae, Togaviridae and Hepeviridae. All of them have a zoonotic origin. Climatic and environmental changes, population mobility, uneven population density, unequal sanitary conditions, change in animal habitats and anthropophilic vectors have led to increased pressure on the host-pathogen-environment system. The more we impact on the nature, the more likely we are to disrupt ecosystems and create conditions for diseases to develop and spread. Conclusion: The possibility suggested by the last pandemic is that only linking the One health approach to the infectious spectrum, dietary interventions, factors determining human susceptibility to infections, vaccinations-universal, unrelated and local, testing platforms for potential pathogens, pre-and probiotics will help us better deal with such challenges. All of them can help us in developing effective control and protection measures against viral pathogens. Differences in emerging and re-emerging infections must be considered. Knowing and properly using the negative interactions between viral and bacterial pathogens and the human microbiota and inhibiting their positive interactions will help us in combining pharmacological, non-pharmacological and dietary interventions in the personalized treatment of patients with diseases caused by viral pathogens.
... It is unquestioned that carrageenan toxicity depends on its molecular weight. Low-molecularweight degraded carrageenans and poligeenans (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) are considered unsafe and remain prohibited, while high-molecular-weight food-grade carrageenans (200-800 kDa) are claimed to be safe for human consumption [15]. However, a growing number of concerns have been raised with regard to food-grade carrageenan toxicity, especially in relation to its detrimental gastrointestinal effects [16][17][18][19][20][21]. ...
... It is unquestioned that carrageenan toxicity depends on its molecular weight. Low-molecularweight degraded carrageenans and poligeenans (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) are considered unsafe and remain prohibited, while high-molecular-weight food-grade carrageenans (200-800 kDa) are claimed to be safe for human consumption [15]. However, a growing number of concerns have been raised with regard to food-grade carrageenan toxicity, especially in relation to its detrimental gastrointestinal effects [16][17][18][19][20][21]. ...
Aim In the current study, hemocompatibility of three major commercially available types of carrageenans (ι, κ and λ) was investigated focusing on eryptosis. Materials and methods: Carrageenans of ι-, κ- and λ-types were incubated with washed erythrocytes (hematocrit 0.4%) at 0–1–5–10 g/L for either 24 h or 48 h. Incubation was followed by flow cytometry-based quantitative analysis of eryptosis parameters, including cell volume, cell membrane scrambling and reactive oxygen species (ROS) production, lipid peroxidation markers and confocal microscopy-based evaluation of intracellular Ca2+ levels, assessment of lipid order in cell membranes and the glutathione antioxidant system. Confocal microscopy was used to assess carrageenan cellular internalization using rhodamine B isothiocyanate-conjugated carrageenans. Results: All three types of carrageenans were found to trigger eryptosis. Pro-eryptotic properties were type-dependent and λ-carrageenan had the strongest impact inducing phosphatidylserine membrane asymmetry, changes in cell volume, Ca2+ signaling and oxidative stress characterized by ROS overproduction, activation of lipid peroxidation and severe glutathione system depletion. Eryptosis induction by carrageenans does not require their uptake by erythrocytes. Changes in physicochemical properties of cell membrane were also type-dependent. No carrageenan-induced generation of superoxide and hydroxyl radicals was observed in cell-free milieu. Conclusions: Our findings suggest that ι-, κ- and λ-types trigger eryptosis in a type-dependent manner and indicate that carrageenans can be further investigated as potential eryptosis-regulating therapeutic agents.
... The primary basis for this efficacy lies in carrageenan's capacity to hinder blood platelet aggregation, demonstrating its anticoagulant activity [27,28]. Different carrageenans excel in other demonstrable bioactivities such as anti-tumor, anti-viral, and immunomodulation activities, and their anti-viral properties are commercially exploited [29]. ...
Seaweed, a miscellaneous group of marine algae, has long been recognized for its rich nutritional composition and bioactive compounds, being considered nutraceutical ingredient. This revision delves into the promising role of seaweed-derived nutrients as a beneficial resource for drug discovery and innovative product development. Seaweeds are abundant sources of essential vitamins, minerals, polysaccharides, polyphenols, and unique secondary metabolites, which reveal a wide range of biological activities. These bioactive compounds possess potential therapeutic properties , making them intriguing candidates for drug leads in various medical applications and pharmaceutical drug development. It explores their pharmacological properties, including antioxidant, anti-inflammatory, antimicrobial, and anticancer activities, shedding light on their potential as therapeutic agents. Moreover, the manuscript provides insights into the development of formulation strategies and delivery systems to enhance the bioavailability and stability of seaweed-derived compounds. The manuscript also discusses the challenges and opportunities associated with the integration of seaweed-based nutrients into the pharmaceutical and nutraceutical industries. Regulatory considerations, sustainability, and scalability of sustainable seaweed sourcing and cultivation methods are addressed, emphasizing the need for a holistic approach in harnessing seaweed's potential. This revision underscores the immense potential of seaweed-derived compounds as a valuable reservoir for drug leads and product development. By bridging the gap between marine biology , pharmacology, and product formulation, this research contributes to the critical advancement of sustainable and innovative solutions in the pharmaceutical and nutraceutical sectors.
... Some examples of microbial polysaccharides include bacterial cellulose, dextran, alginate, pullulan, and chitosan, among others (Xibo et al., 2021). These polysaccharides possess unique properties, such as biocompatibility, biodegradability, and ease of modification, making them suitable candidates for various biomedical and pharmaceutical applications, including nutraceutical delivery (McKim et al., 2019). ...
Polysaccharide-based nanoparticles have garnered significant attention in recent years due to their unique properties and diverse applications in the biomedical field. These nanoparticles are fabricated from natural polysaccharides, such as chitosan, alginate, cellulose, starch, and hyaluronic acid, which offer inherent biocompatibility, biodegradability, and low toxicity, making them attractive candidates for drug delivery, imaging, and tissue engineering. This abstract provides a comprehensive overview of the synthesis, properties, and biomedical applications of polysaccharide-based nanoparticles. The synthesis methods encompass both chemical and physical approaches, including emulsification, nanoprecipitation, ionic gelation, and self-assembly techniques. These methods allow for precise control over nanoparticle size, shape, and surface characteristics, which directly impact their functionality and performance in various applications. Furthermore, polysaccharide-based nanoparticles find utility in medical imaging, providing contrast agents for enhanced diagnostic accuracy and disease monitoring. Additionally, they hold immense potential in tissue engineering, facilitating scaffold fabrication and promoting tissue regeneration through controlled release of growth factors and bioactive molecules.
... These findings support the FTIR analysis and indicate that the ultrasonication did not change the polysaccharide network, although it reduced the intermolecular chain connections. Indeed, the ultrasonication of polysaccharides is beneficial in various industries, such as in food and cosmetics, because it does not significantly affect the molecular weight of the polysaccharide and does not lead to the formation of small fractions of poligeenan, which are known to be toxic [41]. The antiviral activity of the ultrasonicated ἰ-carrageenan fractions with low molecular weights (<10 kDa) was less effective against both HSV-1 and VZV than that of the ultrasonicated fractions with higher molecular weights and the native ἰ-carrageenan ( Figure 8). ...
... These findings support the FTIR analysis and indicate that the ultrasonication did not change the polysaccharide network, although it reduced the intermolecular chain connections. Indeed, the ultrasonication of polysaccharides is beneficial in various industries, such as in food and cosmetics, because it does not significantly affect the molecular weight of the polysaccharide and does not lead to the formation of small fractions of poligeenan, which are known to be toxic [41]. (Figure 8). ...
carrageenan is a linear macroalgal polysaccharide that is well known for its antiviral bioactivity. Although it is considered a candidate for antiviral therapeutics, its application is highly limited due to its low solubility and high viscosity, which lower its adsorption efficiency. With the aim of deriving an active ἰ-carrageenan fragment with an improved adsorption capacity, we studied the effects of ultrasonication on structural changes in ἰ-carrageenan with respect to changes in its bioactivity against herpesviruses. An FTIR analysis revealed that ultrasonication increased the hydrophilicity of ἰ-carrageenan without changing its functional groups, and a rheological analysis demonstrated that it gradually decreased the strength of the polysaccharide gel, which completely lost its gel structure and formed small nanoparticles after 30 min of ultrasonication. Concomitantly with these physicochemical changes, a plaque assay revealed that longer ultrasonication increased the antiviral activity of ἰ-carrageenan against two herpesviruses, namely, HSV-1 and VZV. Finally, we separated the 30-min ultrasonicated ἰ-carrageenan into four fractions and found that fractions with a lower molecular weight were significantly less active against both herpesviruses than those with a higher molecular weight. Our findings show that ultrasonication induces physicochemical changes in ἰ-carrageenan that increase its antiviral bioactivity.
... These studies are summarized in several reviews [36][37][38][39][40]. However, some authors state that the data supporting the toxicity of food-grade CGNs are subject to misinterpretation due to confusion in the nomenclature of CGNs [41]. In particular, many toxicological studies lack clarifications on the molecular weight of CGNs used. ...
... However, formation of toxic low-molecularweight fragments is suggested to occur via acid hydrolysis in the stomach [43]. Nevertheless, human stomach pH is subject to changes depending on fasting state [41]. Secondly, accumulating evidence suggests that CGNs may induce inflammation through modulating gut microbiota [39,40,[44][45][46][47][48]. ...
Purpose of Review
A growing number of studies indicate that a network of regulated cell death (RCD) pathways plays a vital role in tumorigenesis suggesting its targeting to be a promising therapeutic avenue for cancer treatment. In this review, we firstly systematically summarize the current knowledge on the impact of carrageenans on different non-conventional non-apoptotic RCDs and explore a therapeutic potential of carrageenans as RCDs-modulating agents. Furthermore, we cover the knowledge gaps and controversies in our understanding of cell death-related carrageenan-mediated effects and highlight the directions of further research aiming at studying the pharmacological potential of carrageenans.
Recent Findings
A compelling body of evidence indicates that non-apoptotic RCDs, including necroptosis, ferroptosis, pyroptosis, and autophagy-related cell death, are involved in modulating tumorigenesis and immune response in cancer. Recent advances in our understanding of the role of distinct non-apoptotic RCDs suggest that pharmacological modulation of diverse RCDs is a tempting anti-cancer therapeutic strategy. In particular, carrageenans, which are a group of heterogenous anionic hydrocolloids of polysaccharide nature widely used as food additives (E407 and E407a), have been shown to have anti-viral, anti-cancer, and immunomodulatory activity. The anti-cancer activity of carrageenans is attributed to a certain extent to activation of apoptosis, but the effects of carrageenan on other RCD modes, which can be targeted in oncopathology, are poorly summarized.
Summary
Anti-cancer, immunomodulatory, and anti-viral properties of marine polysaccharides carrageenans are at least partly explained by their modulation of RCD modalities, primarily pyroptosis. Thus, carrageenans can be considered promising RCD-regulating agents, which can be therapeutically exploitable. Furthermore, we emphasize the need to consider induction of non-conventional RCDs as one of the possible molecular mechanisms of carrageenan toxicity.
Graphical Abstract
... These compounds are extensively employed in the food, cosmetic, and pharmaceutical sectors. As a result, extracts from red algae containing carrageenans are commercially utilized [47,48]. Carrageenan, illustrated in Figure 1, is a linear polysaccharide composed of sulphated or nonsulphated galactose units linked together through α-1,3-glycosidic and β-1,4-galactose bonds [49]. ...
Seaweeds are abundant sources of diverse bioactive compounds with various properties and mechanisms of action. These compounds offer protective effects, high nutritional value, and numerous health benefits. Seaweeds are versatile natural sources of metabolites applicable in the production of healthy food, pharmaceuticals, cosmetics, and fertilizers. Their biological compounds make them promising sources for biotechnological applications. In nature, hydrocolloids are substances which form a gel in the presence of water. They are employed as gelling agents in food, coatings and dressings in pharmaceuticals, stabilizers in biotechnology, and ingredients in cosmetics. Seaweed hydrocolloids are identified in carrageenan, alginate, and agar. Carrageenan has gained significant attention in pharmaceutical formulations and exhibits diverse pharmaceutical properties. Incorporating carrageenan and natural polymers such as chitosan, starch, cellulose, chitin, and alginate. It holds promise for creating biodegradable materials with biomedical applications. Alginate, a natural polysaccharide, is highly valued for wound dressings due to its unique characteristics, including low toxicity, biodegradability, hydrogel formation, prevention of bacterial infections, and maintenance of a moist environment. Agar is widely used in the biomedical field. This review focuses on analysing the therapeutic applications of carrageenan, alginate, and agar based on research highlighting their potential in developing innovative drug delivery systems using seaweed phycocolloids.
... The safety of carrageenan does not depend on the species of seaweed, the geographic location, and growing season of the seaweed species, this is shown in comparison with the previously published carrageenan toxicity. [27] 4. Conclusion Carrageenan extracted from Kappaphycus alverazii based on the treatment of the algae surface by using enzyme and extracting by using aqueous was effective in the treatment of gastric ulcers that damaged by acid. 1.5% (w/v) carrageenan had a protective effect and regenerated the gastric mucosa of mice that acutely damaged by 10% hydrochloric acid after a 10-day treatment. ...
Polysaccharides of marine algae belong to anion groups such as fucoidan and alginate are known the treating ability of gastric ulcers but carrageenan has not seen the announcement yet. Therefore, the paper focused on the treating ability evaluation of gastric ulcers of carrageenan that was extracted from Kappaphycus alverazii grown in Vietnam. Three acid agent (hydrochloric acid, 5-sulfosalicylic acid, and acetic acid) in various concentration (1, 5, and 10%) was used for causing disease. Various concentration of carrageenan (0.5, 1.0, and 1.5%) was used for the treating of gastric ulcers. Guinea pig (Cavia porcellus) was observed clinical pharmacology (rate of blood sedimentation and gastric disease surgery) on day 5th and 10th after the treatment. The results showed that carrageenan has the treatment effect of gastric ulcers. A concentration of 1.5% (w/v) carrageenan is a suitable choice for the protection of the gastric mucosa of mice that drunk 10% hydrochloric acid after a 10-day treatment. In summary, carrageen extracted from Kappaphycus alverazii grown in Vietnam can completely be used in food and pharmaceutical products, especially in the preparation of drugs, and functional foods to support the treatment of gastric ulcers.
... Carrageenan is degraded by gastric acid in the gastrointestinal tract to produce oligocarrageenan [24]. Therefore, mice were given λ-COS by intraperitoneal injection in this study. ...
Gastric carcinoma is a frequently detected malignancy worldwide, while its mainstream drugs usually result in some adverse reactions, including immunosuppression. λ-carrageenan oligosaccharides (COS) have attracted increasing attention as potential anticancer agents due to their ability to enhance immune function. Our current work assessed the antitumor mechanism of λ-COS using BGC-823 cells. Our findings indicated that λ-COS alone did not have a significant impact on BGC-823 cells in vitro; however, it was effective in inhibiting tumor growth in vivo. When THP-1 cells were pre-incubated with λ-COS and used to condition the medium, BGC-823 cells in vitro displayed a concentration-dependent induction of cell apoptosis, nuclear damage, and the collapse of mitochondrial transmembrane potential. These findings suggested that the antineoplastic effect of λ-COS was primarily due to its immunoenhancement property. Treatment with λ-COS was found to significantly enhance the phagocytic capability of macrophages, increase the secretion of TNF-α and IFN-γ, and improve the indexes of spleen and thymus in BALB/c mice. In addition, λ-COS was found to inhibit the growth of BGC-823-derived tumors in vitro by activating the Par-4 signaling pathway, which may be stimulated by the combination of TNF-α and IFN-γ. When used in combination with 5-FU, λ-COS demonstrated enhanced anti-gastric carcinoma activity and improved the immunosuppression induced by 5-FU alone. These findings suggested that λ-COS could be used as an immune-modulating agent for chemotherapy.
