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Carrageenans are valuable marine polysaccharides derived from specific species of red seaweed (Rhodophyta) widely used as thickening and stabilizing agents across various industries. Kappaphycus alvarezii, predominantly cultivated in tropical countries, is the primary source of kappa-carrageenan. Traditional industrial extraction methods involve alkaline treatment for up to three hours followed by heating, which is inefficient and generates substantial waste. Thus, developing improved extraction techniques would be helpful for enhancing efficiency and reducing environmental impacts, solvent costs, energy consumption, and the required processing time. In this study, we explored innovative extraction methods, such as ultrasound-assisted extraction (UAE) and supercritical water extraction (SFE), together with other extraction methods to produce kappa-carrageenan from a new strain of K. alvarezii from the Philippines. FTIR-ATR spectroscopy was employed to characterize the structure of the different carrageenan fractions. We also examined the physicochemical properties of isolated phycocolloids, including viscosity, and the content of fatty acids, proteins, and carbohydrates. For refined carrageenan (RC), both the traditional extraction method and the UAE method used 1 M NaOH. Additionally, UAE (8% KOH) was employed to produce semi-refined carrageenan (SRC). UAE (8% KOH) produced a high yield of carrageenan, in half the extraction time (extraction yield: 76.70 ± 1.44), and improved carrageenan viscosity (658.7 cP), making this technique highly promising for industrial scaling up. On the other hand, SFE also yielded a significant amount of carrageenan, but the resulting product had the lowest viscosity and an acidic pH, posing safety concerns as classified by the EFSA’s re-evaluation of carrageenan as a food additive.

Carrageenan oligosaccharides (COSs) possess versatile activities and have drawn increasing attention in recent years. Due to their unique structures, COSs have been considered to be potential antibacterial agents and immune stimulators. Herein, we aimed to efficiently prepare the COSs by using a novel carrageenase CgkA from Zobellia uliginosa with high activity and further investigate the effects of dietary supplementation with COSs on the growth performance, serum biochemical parameters and non-specific immunity in Carassius auratus gibelio. The results indicated that the CgkA could effectively degrade the carrageenan into oligosaccharides with DPs of 2–6 and the oligosaccharides exhibited promoting effects on growth performance, serum biochemical index and non-specific immune parameters. After a 6-month feeding trial, the SR (Survival Ratio) was significantly higher in fish fed 0.1% (Diet 1), 0.2% (Diet 2), 0.5% (Diet 3) and 1% (Diet 4) COSs diets than that in the control group (p < 0.05). In addition, the supplementation of COSs decreased the malondialdehyde (MDA) content in the serum and increased the activity of lysozyme (LZM), superoxide dismutase (SOD) and catalase (CAT). In conclusion, COSs as a dietary supplement enhance the growth performance and non-specific immunity of crucian carp and their resistance to diseases.

Different kinds of red algae are enriched with chemically diverse carbohydrates. In particular, a group of sulfated polysaccharides, which were isolated from the cell walls of red algae, gained a large amount of attention due to their broad-spectrum antimicrobial activities. Within that group, carrageenans (CGs) were expected to be the first clinically applicable microbicides that could prevent various viral infections due to their superior antiviral potency and desirable safety profiles in subclinical studies. However, their anticipated beneficial effects could not be validated in human studies. To assess the value of a second attempt at pharmacologically developing CGs as a new class of preventive microbicides, all preclinical and clinical development processes of CG-based microbicides need to be thoroughly re-evaluated. In this review, the in vitro toxicities; in vivo safety profiles; and in vitro, ex vivo, and in vivo antiviral activities of CGs are summarized according to the study volume of their target viruses, which include human immunodeficiency virus, herpesviruses, respiratory viruses, human papillomavirus, dengue virus, and other viruses along with a description of their antiviral modes of action and development of antiviral resistance. This evaluation of the strengths and weaknesses of CGs will help provide future research directions that may lead to the successful development of CG-based antimicrobial prophylactics.

Carrageenan and carrageenan oligosaccharides are red seaweed sulfated carbohydrates with well-known antiviral properties, mainly through the blocking of the viral attachment stage. They also exhibit other interesting biological properties and can be used to prepare different drug delivery systems for controlled administration. The most active forms are λ-, ι-, and κ-carrageenans, the degree and sulfation position being determined in their properties. They can be obtained from sustainable worldwide available resources and the influence of manufacturing on composition, structure, and antiviral properties should be considered. This review presents a survey of the antiviral properties of carrageenan in relation to the processing conditions, particularly those assisted by intensification technologies during the extraction stage, and discusses the possibility of further chemical modifications.

Carrageenan-containing nasal sprays, available over-the-counter (OTC), are often marketed as having anti-viral effects. Carrageenan belongs to the glycosaminoglycan family alongside heparin, and heparin is known to inhibit real-time quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal swabs used to detect SARS-CoV-2. As heparin and carrageenan share structural similarities, this work aimed to investigate the interferent effect of carrageenan on RT-qPCR for SARS-CoV-2 detection across 4 different diagnostic platforms. This work demonstrated that in the presence of carrageenan samples return inaccurate and invalid results on the Seegene STARlet, while qualitative accuracy was maintained on the Cepheid GeneXpert, Roche Cobas LIAT, and Hologic Panther Aptima. Evidence of carrageenan interference on SARS-CoV-2 testing was consistent across two OTC brands and research-grade reconstituted iota-carrageenan, with 80% of results returning invalid regardless of the carrageenan formulation added to the samples. Further, a preliminary in vivo interference study demonstrated an increased Ct value within 15 minutes of carrageenan dosage, with Ct values restored 60 minutes post-application. A direct comparison of carrageenan- and heparin-mediated PCR interference demonstrated that carrageenan PCR interference occurs to a lesser degree, but is not reversible by the addition of heparinase I. As carrageenan is available OTC, interference with PCR testing that causes an increase in false negative results could lead to accidental spread of disease and could therefore have significant public health impacts on community testing of respiratory infectious diseases via PCR.

Carrageenan is an anionic sulfated polysaccharide that accounts for a high content of red seaweed Eucheuma gelatinae. This paper focused on the extraction, optimization, and evaluation of antioxidant activity, rheology characteristics, and physic-chemistry characterization of β-carrageenan from Eucheuma gelatinae. The extraction and the optimization of β-carrageenan were by the maceration-stirred method and the experimental model of Box-Behken. Antioxidant activity was evaluated to be the total antioxidant activity and reducing power activity. The rheology characteristics of carrageenan were measured to be gel strength and viscosity. Physic-chemistry characterization was determined, including the molecular weight, sugar composition, function groups, and crystal structure, through GCP, GC-FID, FTIR, and XRD. The results showed that carrageenan possessed antioxidant activity, had intrinsic viscosity and gel strength, corresponding to 263.02 cps and 487.5 g/cm2, respectively. Antioxidant carrageenan is composed of rhamnose, mannose, glucose, fucose, and xylose, with two molecular weight fractions of 2.635 × 106 and 2.58 × 106 g/mol, respectively. Antioxidant carrageenan did not exist in the crystal. The optimization condition of antioxidant carrageenan extraction was done at 82.35 °C for 115.35 min with a solvent-to-algae ratio of 36.42 (v/w). At the optimization condition, the extraction efficiency of carrageenan was predicted to be 87.56 ± 5.61 (%), the total antioxidant activity and reducing power activity were predicted to 71.95 ± 5.32 (mg ascorbic acid equivalent/g DW) and 89.84 ± 5.84 (mg FeSO4 equivalent/g DW), respectively. Purity carrageenan content got the highest value at 42.68 ± 2.37 (%, DW). Antioxidant carrageenan from Eucheuma gelatinae is of potential use in food and pharmaceuticals.

The COVID-19 pandemic continues to spread around the world and remains a major public health threat. Vaccine inefficiency, vaccination breakthroughs and lack of supply, especially in developing countries, as well as the fact that a non-negligible part of the population either refuse vaccination or cannot be vaccinated due to age, pre-existing illness or non-response to existing vaccines intensify this issue. This might also contribute to the emergence of new variants, being more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity. Hence, the need of effective and viable prevention options to reduce viral transmission is of outmost importance. In this study, we investigated the antiviral effect of iota-, lambda- and kappa-carrageenan, sulfated polysaccharides extracted from red seaweed, on SARS-CoV-2 Wuhan type and the spreading variants of concern (VOCs) Alpha, Beta, Gamma and Delta. Carrageenans as part of broadly used nasal and mouth sprays as well as lozenges have the potential of first line defense to inhibit the infection and transmission of SARS-CoV-2. Here, we demonstrate by using a SARS-CoV-2 spike pseudotyped lentivirus particles (SSPL) system and patient-isolated SARS-CoV-2 VOCs to infect transgenic A549ACE2/TMPRSS2 and Calu-3 human lung cells that all three carrageenan types exert antiviral activity. Iota-carrageenan exhibits antiviral activity with comparable IC50 values against the SARS-CoV-2 Wuhan type and the VOCs. Altogether, these results indicate that iota-carrageenan might be effective for prophylaxis and treatment of SARS-CoV-2 infections independent of the present and potentially future variants.

Antimicrobial resistance (AMR)-related diseases have ruined the lives of many people and the multidrug-resistant bacterial infections have a key role in the mortality associated with antimicrobial resistance (AMR). The focus was shifted to natural resources for the development of antimicrobial compounds in order to overcome this resistance. In this study K-Carrageenan was extracted from Kappaphycus alvarezii and characterized by the Fourier transform infrared (FTIR), Gas chromatography mass spectrometry (GC–MS), Liquid chromatography mass spectrum (LC–MS) and Nuclear Magnetic Resonance (H-NMR) analysis. The antibacterial property of carrageenan was tested using the Minimum Inhibitory Concentration and the bacterial cell growth rate. The results showed higher antibacterial activity of K-Carrageenan against S. aureus , E. coli , P. aeruginosa , P. vulgaris , and V. parahaemolyticus. Well diffusion method, growth curve studies, anti-biofilm studies were done in K-Carrageenan. Intracellular protein molecules and nucleic acid leakage confirmed that 100 µg/mL of K-Carrageenan increase membrane permeability, leading to cell death. At a concentration of 100 µg/mL of K-Carrageenan was non-cytotoxic to RBCs cells and promoted antibacterial and antibiofilm properties against the wound pathogens. From this study, these results determine the strong potential of K-Carrageenan treating MDR bacteria-infected chronic wounds.

Seaweed contains a variety of bioactive compounds; the most abundant of them are polysaccharides, which have significant biological and chemical importance. Although algal polysaccharides, especially the sulfated polysaccharides, have great potential in the pharmaceutical, medical and cosmeceutical sectors, the large molecular size often limits their industrial applications. The current study aims to determine the bioactivities of degraded red algal polysaccharides by several in vitro experiments. The molecular weight was determined by size-exclusion chromatography (SEC), and the structure was confirmed by FTIR and NMR. In comparison to the original furcellaran, the furcellaran with lower molecular weight had higher OH scavenging activities. The reduction in molecular weight of the sulfated polysaccharides resulted in a significant decrease in anticoagulant activities. Tyrosinase inhibition improved 2.5 times for hydrolyzed furcellaran. The alamarBlue assay was used to determine the effects of different Mw of furcellaran, κ-carrageenan and ι-carrageenan on the cell viability of RAW264.7, HDF and HaCaT cell lines. It was found that hydrolyzed κ-carrageenan and ι-carrageenan enhanced cell proliferation and improved wound healing, whereas hydrolyzed furcellaran did not affect cell proliferation in any of the cell lines. Nitric oxide (NO) production decreased sequentially as the Mw of the polysaccharides decreased, which indicates that hydrolyzed κ-Carrageenan, ι-carrageenan and furcellaran have the potential to treat inflammatory disease. These findings suggested that the bioactivities of polysaccharides were highly dependent on their Mw, and the hydrolyzed carrageenans could be used in new drug development as well as cosmeceutical applications.

Microglial inflammation plays an essential role in neurodegenerative disease. Our previous studies had shown that κ-carrageenan oligosaccharides (KOS) could inhibit the excessive activation of microglia that induced by LPS, while the interrelated mechanisms were still indistinct. Therefore, we detected the inflammatory signaling pathway on LPS-activated microglia that pretreat by different content of KOS to reveal the mechanism on KOS's inhibition of microglia inflammatory response. ELISA was used to detect the effects of KOS on the secretion of interleukin-1 (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PG-2) by LPS-activated microglia, respectively. The production of reactive oxygen species (ROS) and nitric oxide (NO) in microglia cells was detected by flow cytometry, and the protein expression of immunoinflammation-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protected the microglia from the over-activated inflammatory by inhibiting the release of inflammatory cytokines and the oxidative stress response. And KOS could reduce the expression of the protein that related to the TLR4/NF-κB and p38/JNK MAPKs pathways activated by LPS in microglia. However, there may be no specific target of KOS in cells. Therefore, KOS, a natural algal source oligosaccharide, has immunomodulatory effects and can be used as a potential intervention therapy for inflammatory related neurodegenerative diseases.