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Seaweeds are important source of bioactive compounds, including sulfated polysaccharides (SP). Because of their structural heterogeneity, these compounds are promising sources of anticancer compounds. SP from brown and red seaweeds have shown antimelanoma activity in different in vitro and in vivo models. However, SP from green seaweed are still poorly evaluated. Therefore, SP were extracted from the green alga Caulerpa cupressoides var. flabellata, and their antiproliferative, anti-migratory, and inhibitory effect on melanin production on B16-F10 melanoma cells was evaluated. Cell assays, including flow cytometry, demonstrated that SP (100–1000 μg mL−1) are non-cytotoxic, do not induce apoptosis or necrosis, and do not interfere with cell cycle. However, SP (1000 μg mL−1) were found to significantly inhibit cell colony formation (80–90%), cell migration (40–75%), and melanin production (~ 20%). In summary, these results showed that SP inhibited important melanoma development events without cytotoxicity effects, suggesting that C. cupressoides may be an important source of SP with antitumor properties.

Oxidative stress is the cause of numerous diseases in humans, therefore, there has been a continuous search for novel antioxidant molecules. Fungal chitosan is an attractive molecule that has several applications (antifungal, antibacterial, anticancer and antiparasitic action) owing to its unique characteristics, however, it exhibits low antioxidant activity. The aim of this study was to obtain fungal chitosan (Chit-F) from the fungus Rhizopus arrhizus and synthesize its derivative, fungal chitosan-gallic acid (Chit-FGal), as a novel antioxidant chitosan derivative for biomedical use. A low molecular weight Chi-F (~3.0 kDa) with a degree of deacetylation of 86% was obtained from this fungus. Chit-FGal (3.0 kDa) was synthesized by an efficient free radical-mediated method using hydrogen peroxide (H2O2) and ascorbic acid. Both Chit-F and Chit-FGal showed similar copper chelating activities, however, Chit-FGal was more efficient as an antioxidant, exhibiting twice the total antioxidant capacity than Chi-F (p &lt, 0.05). Furthermore, H2O2 (0.06 M) promoted a 50% decrease in the viabilities of the 3T3 fibroblast cells. However, this effect was abolished in the presence of Chit-FGal (0.05–0.25 mg/mL), indicating that Chit-FGal protected the cells from oxidative damage. These results suggest that Chit-FGal may be a promising agent to combat oxidative stress.

Melanoma is the most lethal form of skin cancer, with a worldwide increase in incidence. Despite the increased overall survival of metastatic melanoma patients given recent advances in targeted and immunotherapy, it still has a poor prognosis and available treatment options carry diverse severe side effects. Polysaccharides from seaweed have been shown to exert antitumor activities. Here we show in vitro and in vivo antitumor activities of a sulfated homogalactan (named 3G4S) from Codium isthmocladum seaweed in the B16-F10 murine melanoma cell line. 3G4S did not induce cytotoxicity or proliferation changes; however, it was able to reduce solid tumor growth and metastasis, while not inducing side effects in mice. B16-F10 cells traits related to the metastatic cascade were also impaired by 3G4S, reducing cell invasion, colony-forming capacity and membrane glycoconjugates. Therefore, 3G4S shows promising antitumor activities without the commonly associated drawbacks of cancer treatments and can be further explored.

Cell wall polysaccharides from filamentous fungi and yeasts have been reported as antioxidant and antiproliferative polymers. Thus, we evaluated these activities from cell wall polysaccharides from Kluyveromyces marxianus CCT7735. By using a centrifugal filter, a 203 kDa α-d-mannan (KMM-5) was obtained. KMM-5 exhibited no effect on HeLa cells and a weak antiproliferative activity against Hep-G2 cells. In addition, at higher concentrations, it presented a cytotoxicity to the normal cell line, 3T3. However, KMM-5 showed copper- and iron-chelating abilities, the latter of which presented improved activity. By using 2D-NMR COSY, HSQC edited and HMBC experiments, a structure arrangement was proposed. The main chain was formed by 6)-α-d-Manp-(1 → 6) units substituted at the 2-O-position by non-reducing terminals α-d-Manp-(1 → 2) and by a branched tetrasaccharide. The latter was formed by an internal 2)-α-d-Manp-(1 → 2) unit with linked to it a 2,3)-α-d-Manp-(1 → 2) unit substituted at the 2-O-position by a non-reducing terminal α-d-Manp-(1 → 2), and at the 3-O-position by a non-reducing terminal α-d-Manp-(1 → 3). In conclusion, we considered K. marxianus CCT7735 a source of natural and renewable polysaccharides with pharmacological properties.

Sulfated polysaccharides (SPs) obtained from green seaweeds are structurally heterogeneous molecules with multifunctional bioactivities. In this work, two sulfated and pyruvated galactans were purified from Caulerpa cupressoides var. flabellata (named SP1 and SP2), and their immunostimulatory effect was evaluated using cultured murine macrophage cells. Both SPs equally increased the production of nitric oxide, reactive oxygen species, and the proinflammatory cytokines TNF-&alpha, and IL-6. NMR spectroscopy revealed that both galactans were composed primarily of 3)-&beta, d-Galp-(1&rarr, 3) units. Pyruvate groups were also found, forming five-membered cyclic ketals as 4,6-O-(1'carboxy)-ethylidene-&beta, d-Galp residues. Some galactoses are sulfated at C-2. In addition, only SP2 showed some galactose units sulfated at C-4, indicating that sulfation at this position is not essential for the immunomodulatory activity of these galactans. Overall, the data showed that the galactans of C. cupressoides exhibited immunostimulating activity with potential therapeutic applications, which can be used in the development of new biomedical products.

Xylan is one of the most abundant hemicellulose constituents in the plant kingdom. We extracted xylan from corn cobs (XCC) using ultrasound. The structure of XCC was determined by NMR analysis, which revealed a composition of xylose:glucose:arabinose:galactose:mannose:glucuronic acid in a molar percentage ratio of 48:21:16:10:2.5:2.5. XCC induced the proliferation of murine macrophage cells (RAW 264.7) and inhibited the proliferation of human lung adenocarcinoma epithelial cells (A549) by 20% and human cervical adenocarcinoma cells (HeLa) by 60%. Several cell death-associated morphological changes were observed after the exposure of HeLa cells to XCC for 24 h. In addition, by using fluorescent probes, we observed a larger number of irregular and pyknotic nuclei with condensed chromatin bodies (nuclear condensation). FACS analysis showed an increase in the number of annexin V-positive and propidium iodide (PI)-positive cells (37.0%) in the presence of XCC compared with that of the negative control cells (5.0%). XCC also increased the ratio of Bax:Bcl-2 (3.5:1) and the levels of cytochrome c, caspase 3, and apoptosis-inducing factor (AIF) in treated cells. Therefore, the results demonstrated the antiproliferative potential of XCC, which induced apoptosis in HeLa cells.

Leaves of Arctium lappa contain several mono- and dicaffeoylquinic acids, as evaluated by liquid chromatography-mass spectrometry. In order to investigate the protection on gastric mucosa against ulcers, rats were treated with fractions from leaf extract prior to ethanol-induced ulcers. The original fraction obtained as ethanol soluble fraction from hot aqueous extract was able to protect de gastric mucosa, and this effect was retained in the ethyl acetate fraction, obtained from liquid/liquid fractionation. The main compound in this fraction was isolated and chemically characterized by nuclear magnetic resonance and mass spectrometry, assisted by isopropylidene derivatization which gave rise a mass increment of 40 units. Therefore, the underivatized compound that had m/z 515.119 [M-H](-) was shifted to m/z 555.151, being confirmed as 1,3-O-dicaffeoylquinic acid, which presented an ED50 of 57 µg kg(-1) on gastric protection, lesser than the therapeutic concentration of omeprazole (40 mg kg(-1)).

Two sulfated polysaccharides (SPs), F2 and F3, isolated from Codium isthmocladum were found to contain galactose, sulfate, and pyruvate. The apparent molecular weights of F2 and F3 were determined to be 62 and 61 kDa, respectively. NMR spectroscopy combined with chemical analysis showed that F2 and F3 have the same structural features. However, F3 showed higher sulfate/sugar ratio (1/2.6) than F2 (1/4). F2 and F3 are essentially (1 → 3)-β-D-galactans with some branching at C6. Pyruvylation occurs at O3 and O4, forming 3,4-O-(1-carboxyethylidene)-β-D-Galp residues; some of these pyruvylated residues contain sulfate groups at C6. Some non-branching residues contain sulfate at C4. None of the SPs exhibited antioxidant activity. MTT results indicated that 1 mg/mL of both SPs about 40% of PANC-1 cell viability. At 10 μg/mL, F2 and F3 had 1.7-fold longer clotting times compared to that of Clexane® at the same concentration. The higher sulfate content of F3 is not a determining factor for pharmacological activities of galactans, considering that both F2 and F3 exerted the effects.

In this study, we evaluated the effect of different doses of polysaccharides extracted from Caripia montagnei mushroom at different intervals of treatment on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The FT-IR analysis and NMR showed that the polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed the reduction of colonic lesions in all groups treated with the glucans. Such glucans significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that the glucans from C. montagnei acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01) and myeloperoxidase (p < 0.001), a result confirmed by the reduction of cellular infiltration observed microscopically. The increase of catalase activity possibly indicates a protective effect of these glucans on colonic tissue, confirming their anti-inflammatory potential.

Fucan (SV1) sulfated polysaccharides from the brown algae Sargassum vulgare were extracted, fractionated in acetone and examined with respect to chemical composition, anticoagulant, anti-inflammatory, antithrombotic effects and cellular proliferation. These polysaccharides contain low levels of protein, high level of carbohydrate and sulfate. Monosaccharides analysis revealed that SV1 was composed of fucose, galactose, xylose, glucuronic acid and mannose. SV1 polysaccharide prolonged activated partial thromboplastin time (aPTT) and exhibited high antithrombotic action in vivo, with a concentration ten times higher than heparin activity. PSV1, a purified form in gel filtration showed very low biological activities. SV1 stimulated the enzymatic activity of FXa. Its action on DPPH radical scavenging activity was 22%. This polymer has no cytotoxic action (hemolytic) on ABO and Rh blood types in different erythrocyte groups. It displays strong anti-inflammatory action at all concentrations tested in the carrageenan-induced paw edema model, demonstrated by reduced edema and cellular infiltration.

Gold nanorods (AuNRs) are suitable for constructing self-assembled structures for the development of biosensing devices and are usually obtained in the presence of cetyltrimethylammonium bromide (CTAB). Here, a sulfated chitosan (ChiS) and gum arabic (GA) were employed to encapsulate CTAB/AuNRs with the purpose of studying the interactions of the polysaccharides with CTAB, which is cytotoxic and is responsible for the instability of nanoparticles in buffer solutions. The presence of a variety of functional groups such as the sulfate groups in ChiS and the carboxylic groups in GA, led to efficient interactions with CTAB/AuNRs as evidenced through UV-vis and FTIR spectroscopies. Electron microscopies (HR-SEM and TEM) revealed that nanoparticle clusters were formed in the GA-AuNRs sample, whereas individual AuNRs, surrounded by a dense layer of polysaccharides, were observed in the ChiS-AuNRs sample. Therefore, the presented work contributes to the understanding of the driving forces that control the surface interactions of the studied materials, providing useful information in the building-up of gold self-assembled nanostructures.

Seaweeds are a source of several biopolymers widely used in cosmetics, food, and pharmaceuticals. Among them are sulfated polysaccharides, which have several biological/pharmacological activities, such as antioxidant and anticoagulant activities. In the present study, four sulfated polysaccharides, denominated CCB-F0.3, CCB-F0.5, CCB-F1.0, and CCB-F2.0, were obtained from the chlorophyte Caulerpa cupressoides var. flabellata through proteolytic digestion, followed by acetone fractionation and molecular sieving in Sephadex G-100. Chemical analyses showed that CCB-F0.5 had the highest sulfate/sugar ratio (0.73), whereas CCB-F1.0 exhibited the lowest ratio (0.23). Polysaccharides from C. cupressoides displayed a heterogeneous constitution of monosaccharides, with galactose as the main sugar unit (except for CCB-F2.0). The presence of sulfated polysaccharides was confirmed by electrophoretic and infrared analyses. Sulfated polysaccharides showed no activity in superoxide and hydroxyl radical scavenging; however, they did demonstrate total antioxidant capacity and ferrous chelating activity. Caulerpa polysaccharides also exhibited anticoagulant activity in the intrinsic (activated partial thromboplastin time (aPTT) test) and extrinsic pathway (prothrombin time (PT) test). In the aPTT test, all polysaccharides displayed considerable dose-dependent activity. A significant result was the aPTT activity of the polysaccharides CCB-F0.3 and CCB-F0.5, which was similar to that of Clexane®, a commercial low molecular weight heparin. In addition, CCB-F0.3 and CCB-F0.5 showed PT activity. Sulfated polysaccharides from C. cupressoides are therefore promising antioxidant agents in preventing the formation of reactive oxygen species and for their possible use in anticoagulant therapy.

Fucan is a term used to denominate a family of sulfated polysaccharides rich in L-fucose. The brown alga Spatoglossum schröederi, Dictyotaceae, synthesizes three heterofucans named A, B, and C. Fucan A is a non-anticoagulant heterofucan which possesses potent antithrombotic (in vivo) and antiproliferative (in vitro) activities. However, its toxicity in vivo has not been determined. The present study examined the acute and subchronic toxicity of the fucan A in Wistar rats after subcutaneous administration. After that, the animals were killed and examined. The results showed in the acute study that fucan A did not cause general adverse effects and mortality in the concentrations 0, 20, 100, 1000, and 2000 µg/g body weight per rat for seven days. Regarding the subchronic study, the data showed that the fucan A did not cause any change in hematological and biochemistry parameters, as well as in the morphology, and in the size of the rat's organs analyzed at a concentration of 20 µg/g body weight per rat during a 62-day period. In conclusion, this study indicates this heterofucan is a compound with potential pharmacological value that has no toxicity in vivo.

In the present study, six families of sulfated polysaccharides were obtained from seaweed Dictyopteris delicatula by proteolytic digestion, followed by acetone fractionation and molecular sieving on Sephadex G-100. Chemical analyses demonstrated that all polysaccharides contain heterofucans composed mainly of fucose, xylose, glucose, galactose, uronic acid, and sulfate. The fucans F0.5v and F0.7v at 1.0 mg/mL showed high ferric chelating activity (∼45%), whereas fucans F1.3v (0.5 mg/mL) showed considerable reducing power, about 53.2% of the activity of vitamin C. The fucan F1.5v presented the most prominent anticoagulant activity. The best antiproliferative activity was found with fucans F1.3v and F0.7v. However, F1.3v activity was much higher than F0.7v inhibiting almost 100% of HeLa cell proliferation. These fucans have been selected for further studies on structural characterization as well as in vivo experiments, which are already in progress.

Sulfated polysaccharides from 11 species of tropical marine algae (one edible specie of Rhodophyta, six species of Phaeophyta and four species of Chlorophyta) collected from Natal city coast (Northeast of Brazil) were evaluated for their anticoagulant, antioxidant and antiproliverative in vitro activities. In the activated partial thromboplastin time (APTT) test, which evaluates the intrinsic coagulation pathway, seven seaweeds presented anticoagulant activity. Dictyota cervicornis showed the highest activity, prolonging the coagulation time to double the baseline value in the APTT with only 0.01 mg/100 microl of plasma, 1.4-fold lesser than Clexane, a low molecular weight heparin. In the protrombin time (PT) test, which evaluates the extrinsic coagulation pathway, only Caulerpa cupresoides showed anticoagulant activity. All species collected showed antioxidant activities. This screening emphasized the great antioxidant potential (total capacity antioxidant, power reducing and ferrous chelating) of four species: C. sertularioide; Dictyota cervicornis; Sargassum filipendula and Dictyopteris delicatula. After 72 h incubation, HeLa cell proliferation was inhibited (p