Cerium oxide nanoparticles: Chemical properties, biological effects and potential therapeutic opportunities (Review).

The chemistry of pure cerium oxide (CeO2-x) nanoparticles has been widely studied since the 1970s, especially for chemical catalysis. CeO2-x nanoparticles have been included in an important class of industrial metal oxide nanoparticles and have been attributed a range of wide applications, such as ultraviolet absorbers, gas sensors, polishing agents, cosmetics, consumer products, high-tech devices and fuel cell conductors. Despite these early applications in the field of chemistry, the biological effects of CeO2-x nanoparticles were only explored in the 2000s. Since then, CeO2-x nanoparticles have gained a spot in research related to various diseases, especially the ones in which oxidative stress plays a part. Due to an innate oxidation state variation on their surface, CeO2-x nanoparticles have exhibited redox activities in diseases, such as cancer, acting either as an oxidizing agent, or as an antioxidant. In biological models, CeO2-x nanoparticles have been shown to modulate cancer cell viability and, more recently, cell death pathways. However, a deeper understanding on how the chemical structure of CeO2-x nanoparticles (including nanoparticle size, shape, suspension, agglomeration in the medium used, pH of the medium, type of synthesis and crystallite size) influences the cellular effects observed remains to be elucidated. In the present review, the chemistry of CeO2-x nanoparticles and their impact on biological models and modulation of cell signalling, particularly focusing on oxidative and cell death pathways, were investigated. The deeper understanding of the chemical activity of CeO2-x nanoparticles may provide the rationale for further biomedical applications towards disease treatment and drug delivery purposes.

Recent Progress in Understanding the Impact of Food Processing and Storage on the Structure-Activity Relationship of Fucoxanthin.

Fucoxanthin, a brown algae carotenoid, has attracted great interest because of its numerous biological activities supported by in vitro and in vivo studies. However, its chemical structure is susceptible to alterations when subjected to food processing and storage conditions, such as heat, oxygen, light, and pH changes. Consequently, these conditions lead to the formation of fucoxanthin derivatives, including cis-isomers, apo-fucoxanthinone, apo-fucoxanthinal, fucoxanthinol, epoxides, and hydroxy compounds, collectively known as degradation products. Currently, little information is available regarding the stability and functionality of these fucoxanthin derivatives resulting from food processing and storage. Therefore, enhancing the understanding of the biological effect of fucoxanthin derivatives is crucial for optimizing the utilization of fucoxanthin in various applications and ensuring its efficacy in potential health benefits. To this aim, this review describes the main chemical reactions affecting the stability of fucoxanthin during food processing and storage, facilitating the identification of the major fucoxanthin derivatives. Moreover, recent advancements in the structure-activity relationship of fucoxanthin derivatives will be critically assessed, emphasizing their biological activity. Overall, this review provides a critical updated understanding of the effects of technological processes on fucoxanthin stability and activity that can be helpful for stakeholders when designing processes for food products containing fucoxanthin.

Isolation, NMR characterization and bioactivity of a (4-O-methyl-α-D-glucurono)-ß-D-xylan from Campomanesia xanthocarpa Berg fruits.

Hemicellulose-type polysaccharides were isolated from Campomanesia xanthocarpa fruits by alkaline extraction and submitted to fractionation processes giving rise to eluted (GE-300) and retained (GR-300) fractions. GE-300 presented a mixture of galactoglucomannans (GGM) and glucuronoxylans (MGX), while the GR-300 fraction is composed only of MGX. In this way, the chemical structure of MGX, investigated by 1D 1H, 13C and 2D 1H-13C HSQC, 1H-1H COSY and 1H-13C HMBC NMR spectroscopy, revealed that the chemical structure of polysaccharide is a (4-O-methyl-α-D-glucurono)-D-xylan. Deep and precise NMR chemical shift determination of clean and specific 1H NMR glycosyl units were developed by 1D TOCSY and 1D NOESY analysis. This approach demonstrated unequivocally that 4-O-methyl-α-D-glucopyranosyl uronic acid group is linked to O-2 of a (1 â†’ 4)-ß-D-xylan in the main chain. Furthermore, MGX scavenged DPPH radical (0.5 to 1.0 mg mL-1) and was not cytotoxic to human dermal fibroblasts at concentrations up to 1.0 mg mL-1, as demonstrated by neutral red and crystal violet assays, evidencing in vitro biocompatibility. The structure elucidation of GR-300 together with its bioactivity assessment contributed to better understand the chemical characteristics of C. xanthocarpa hemicelluloses and may provide structural basis for future structure-property studies.

The kinetics of formation of resveratrol-ß-cyclodextrin-NH2 and resveratrol analog-ß-cyclodextrin-NH2 supramolecular complexes.

The determination of the kinetics of inclusion processes is significant for the application of inclusion complexes as carriers for bioactive molecules. We determined the kinetic parameters of inclusion between modified ß-cyclodextrin (ß-CD-NH2) and the polyphenols resveratrol (RES) and its structural analog (RESAn1), using the real-time analysis of surface plasmon resonance. The association and dissociation rate constants (ka and kd) showed that RESAn1 inclusion and its dissociation from ß-CD-NH2 were faster than a similar process for RES ( [Formula: see text]  = 3.10∙104 ± 0.14 M-1s-1, [Formula: see text] =1.87∙103 ± 0.11 M-1s-1; [Formula: see text] =0.39 ± 0.02 s-1, [Formula: see text] =0.30 ± 0.02 s-1, at 25 °C). The activated complex formation was also affected by the structural differences between the polyphenols, as showed by the activation energies of the association step ( [Formula: see text] 14.81 ± 0.64 kJ∙mol-1, [Formula: see text] -15.01 ± 0.75 to 82.35 ± 4.47 kJ∙mol-1). These effects of polyphenol structural differences are due to the desolvation process of interacting molecules. These results elucidate the role of small group to the dynamics of the molecular inclusion of ß-CD.

Advances in microalgal cell wall polysaccharides: a review focused on structure, production, and biological application.

Microalgae have been shown to be useful in several biotechnological fields due to their feasible cultivation and high-value biomolecules production. Several substances of interest produced by microalgae, such as: proteins, lipids, and natural colorants, have already been explored. Based on the continuing demand for new natural molecules, microalgae could also be a valuable source of polysaccharides. Polysaccharides are extremely important in aquaculture, cosmetics, pharmaceutical, and food industries, and have great economic impact worldwide. Despite this, reviews on microalgal polysaccharide production, biological activity, and chemical structure are not abundant. Moreover, techniques of microalgal cultivation, coupled with carbohydrate production, need to be clarified in order to develop forward-looking technologies. The present review provides an overview of the main advances in microalgal cell wall polysaccharide production, as well as their associated potential biological applications and chemical structure. Several studies on future prospects, related to microalgae are presented, highlighting the key challenges in microalgal polysaccharide production.

An α-D-galactan and a ß-D-glucan from the mushroom Amanita muscaria: Structural characterization and antitumor activity against melanoma.

Polysaccharides α-D-galactan (GAL-Am) and ß-D-glucan (GLC-Am) were obtained from Amanita muscaria fruiting bodies. They were purified using different methodologies, such as Fehling precipitation (for both fractions), freeze-thawing process and ultrafiltration (for GLC-Am). Results showed that the GAL-Am has (1 â†’ 6)-linked Galp main chain branched at O-2 by terminal Galp units and has not been previously reported. Besides, GLC-Am has (1 â†’ 3)-linked Glcp in the main chain, substituted at O-6 by (1 â†’ 6)-linked ß-Glcp units. Both are water-soluble, with 9.0 × 103 g/moL and 1.3 × 105 g/moL, respectively. GAL-Am and GLC-Am presented a selective proliferation reduction against B16-F10 melanoma cell line, not affecting non tumoral BALB/3T3 fibroblast cell line. Furthermore, both fractions reduced clonogenic capacity of melanoma cell line over an extended period of time. These results were obtained without modulations in B16-F10 cell adhesion, reinforcing the biological activities towards cell proliferation impairment and eliciting these polysaccharides as promising compounds to further exploration of their antimelanoma properties.

Chemical structure of native and modified sulfated heterorhamnans from the green seaweed Gayralia brasiliensis and their cytotoxic effect on U87MG human glioma cells.

A water-soluble sulfated heterorhamnan (Gb1) was isolated from the green seaweed Gayralia brasiliensis and purified by ultrafiltration, yielding a homogeneous polysaccharide (Gb1r). Both fractions contained rhamnose, xylose, galacturonic and glucuronic acids, galactose, and glucose. Chemical and spectroscopic methods allowed the determination of Gb1 and Gb1r chemical structure. Their backbones were constituted by 3-, 2-, and 2,3-linked rhamnosyl units (1:0.49:0.13 and 1:0.58:0.17, respectively), which are unsulfated (13.5 and 14.6%), disulfated (16.6 and 17.8%) or monosulfated at C-2 (8 and 8.6%) and C-4 (24.5 and 23.4%). Gb1 was oversulfated giving rise to Gb1-OS, which presented ~2.5-fold higher content of disulfated rhamnosyl units than Gb1, as determined by methylation analyses and NMR spectroscopy. Gb1 and Gb1-OS potently reduced the viability of U87MG human glioblastoma cells. Gb1 caused cell cycle arrest in the G1 phase, increased annexin V-stained cells, and no DNA fragmentation, while Gb1-OS increased the percentage of cells in the S and G2 phases and the levels of fragmented DNA and cells double-stained with annexin V/propidium iodide, suggesting an apoptosis mechanism. The results suggest that the different effects of Gb1 and Gb1-OS were related to differences in the sulfate content and position of these groups along the polysaccharide chains.

Saponin production from Quillaja genus species. An insight into its applications and biology

Quillaja genus (Quillajaceae family) is endemic to South America, where is represented by two species, Quillaja saponaria and Quillaja brasiliensis. One outstanding characteristic of these forest tree species is their production of saponins, a family of amphipathic glycosides, involved in the defensive response of plants against biotic and abiotic factors. Saponins are metabolites of economic importance due to their chemical and physical properties. Basic and applied research efforts performed during the last decades, mainly on Q. saponaria, have placed these compounds as an important raw material in industrial areas, such as food and beverage, cosmetics, vaccine production, biopesticides, among others. In this review, we summarize information on saponins from Quillaja species during the last years, analyzing current developments by application areas, as well as their chemical composition and properties. We also describe the general advances in revealing saponin biosynthesis pathways, related genes and Quillaja genomes, as well as the conservation status, domestication processes, and perspectives in the context of implementing genetic improvement programs.

Saponin production from Quillaja genus species. An insight into its applications and biology

Quillaja genus (Quillajaceae family) is endemic to South America, where is represented by two species, Quillaja saponaria and Quillaja brasiliensis. One outstanding characteristic of these forest tree species is their production of saponins, a family of amphipathic glycosides, involved in the defensive response of plants against biotic and abiotic factors. Saponins are metabolites of economic importance due to their chemical and physical properties. Basic and applied research efforts performed during the last decades, mainly on Q. saponaria, have placed these compounds as an important raw material in industrial areas, such as food and beverage, cosmetics, vaccine production, biopesticides, among others. In this review, we summarize information on saponins from Quillaja species during the last years, analyzing current developments by application areas, as well as their chemical composition and properties. We also describe the general advances in revealing saponin biosynthesis pathways, related genes and Quillaja genomes, as well as the conservation status, domestication processes, and perspectives in the context of implementing genetic improvement programs.(AU)

Sulfated polysaccharide from the red algae Gelidiella acerosa: Anticoagulant, antiplatelet and antithrombotic effects.

A sulfated polysaccharide from the red algae Gelidiella acerosa (GaSP) was obtained through enzymatic extraction and subjected to chemical characterization by HPSEC, elemental microanalysis, FT-IR and NMR spectroscopies. The GaSP anticoagulant activity was investigated through APTT and PT tests and platelet aggregation assessed by turbidimetry. The antithrombotic and hemorrhagic activities were evaluated by venous thrombosis and hemorrhagic tendency models, respectively. FT-IR and NMR demonstrated that GaSP is a sulfated agaran. HPSEC and elemental microanalysis revealed a peak molar mass of 284.8 kDa and a degree of sulfation of 0.63, respectively. This molecule prolonged the coagulation time in 2.1 times and inhibited the platelet aggregation by 45%. Furthermore, it showed significant dose-dependent antithrombotic effect of 40%, 64% and 80% at 0.1, 0.5 and 1 mg/kg, respectively, without hemorrhage. These results suggest that GaSP has promising antithrombotic.

Inhibition of Leishmania amazonensis arginase by fucogalactan isolated from Agrocybe aegerita mushroom.

The inhibition of arginase from Leishmania spp. is considered a promising approach to the leishmaniasis treatment. In this study, the potential of a fucogalactan isolated from the medicinal mushroom Agrocybe aegerita was evaluated against arginase (ARG) from Leishmania amazonensis. The polysaccharide was obtained via aqueous extraction, and purified by freeze thawing and precipitation with Fehling solution. Its chemical structure was established by monosaccharide composition, methylation analysis, partial acid hydrolysis, and NMR spectroscopy. The data indicated that it is a fucogalactan (FG-Aa; Mw = 13.8 kDa), having a (1→6)-linked α-D-Galp main-chain partially substituted in O-2 by non-reducing end-units of α-L-Fucp. FG-Aa showed significant inhibitory activity on ARG with IC50potency of 5.82 ± 0.57 µM. The mechanism of ARG inhibition by the heterogalactan was the competitive type, with Kiof 1.54 ± 0.15 µM. This is the first report of an inhibitory activity of arginase from L. amazonensis by biopolymers, which encourages us to investigate further polysaccharides as a new class of ARG inhibitors.

Chemical structure of a partially 3-O-methylated mannofucogalactan from edible mushroom Grifola frondosa.

An unusual heteropolysaccharide was isolated from the fruiting bodies of the medicinal mushroom Grifola frondosa, via successive cold aqueous extraction, followed by fractionation through freeze-thawing, precipitation with Fehling solution and dialysis using a membrane with a size exclusion cut-off of 500 kDa. Its chemical structure was determined based on total acid hydrolysis, methylation analysis and NMR studies. The mannofucogalactan had a molar mass of 15.9 × 103 g mol-1, which was determinate by HPSEC-MALLS. This heteropolymer showed to have a main chain of (1 → 6)-linked α-d-Galp partially substituted at O-2 by 3-O-α-d-mannopyranosyl-α-l-fucopyranosyl groups and in a minor proportion with α-l-Fucp single-unit side chains. Moreover, the presence of 3-O-Me-Galp units could also be observed in the main chain of the G. frondosa mannofucogalactan.

Partially methylated galactans containing different proportions of 3-O-methyl-galactose from Pleurotus citrinopileatus.

Pleurotus citrinopileatus, popularly known as "golden oyster mushroom" have medicinal properties, which are attributed mainly to the presence of bioactive polysaccharides. In this work, two partially 3-O-methylated galactans were isolated from the fruiting bodies of this fungus, via successive aqueous extraction, followed by fractionation by freeze-thawing, and precipitation of soluble material with Fehling solution. The structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. The polysaccharides were characterized as linear, partially 3-O-methylated (1 → 6)-linked α-galactopyranans, containing only Gal and 3-O-Me-Gal, in 2:1 and 1:1 molar ratios, with molar masses of 37.6 × 103 g/mol and 28.5 × 103 g/mol, respectively. Similar structures have been described for other Pleurotus spp., but showing a lower content of 3-O-Me-Gal.

Natural antioxidant extracts as food preservatives.

The food industry is becoming more specialized and processing methods are continuously being developed to meet consumer needs. Consumers demand products that are safe and preferably free of synthetic additives. These additives are associated with health effects, in most cases without reasonable justification. Consequently, consumers are looking for clearly labelled products that guarantee the absence of synthetic additives. This has led to the need to search for natural additives, which the food industry claims arenatural antioxidant preservatives. The sources of natural antioxidants can be extremely varied, because practically all plants contain antioxidants that allow them to protect themselves from solar radiation and pests, as well as to regulate the production of chemical energy. However, the best alternatives for the food industry are fruits and spices, because they are already foods themselves. This article will describe fruits and spices considered as important sources of phenolic antioxidants. The main medicinal properties are related to phenolic compounds and their uses as additives, depending on their chemical structure.

Safe therapeutics of murine melanoma model using a novel antineoplasic, the partially methylated mannogalactan from Pleurotus eryngii.

A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A mannogalactan having a main chain of (1→6)-linked α-d-galactopyranosyl and 3-O-methyl-α-d-galactopyranosyl residues, both partially substituted at OH-2 by ß-d-Manp (MG-Pe) single-unit was found. Biological effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells invasion. Also, 50mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up to 10days decreased in 60% the tumor volume compared to control. Additionally, no changes were observed when biochemical profile, complete blood cells count (CBC), organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti-melanoma molecule capable of switching melanoma cells to a non-invasive phenotype with no toxicity to melanoma-bearing mice.

Protective Effect of the Sulfated Agaran Isolated from the Red Seaweed Laurencia aldingensis Against Toxic Effects of the Venom of the Snake, Lachesis muta.

Snakebite is a serious occupational hazard affecting mainly rural populations of tropical and subtropical developing countries. Lachesis muta (Bushmaster) bites are extremely serious but are rarely reported in the literature. Bushmaster envenomings are characterized by intense local pain, edema, neurotoxicity, hypotension, local hemorrhage, and dramatic systemic alterations. Antivenom treatment has regularly been used for more than a century; however, it fails to neutralize local tissue damage and hemorrhage, leading to morbidity or disabilities in victims. Thus, the production and clinical use of antivenom must be improved. The present work characterizes, for the first time, a sulfated polysaccharide from the red seaweed, Laurencia aldingensis, including its neutralizing effect on some toxic activities of L. muta venom. Chemical and spectroscopic analyses showed that L. aldingensis produces sulfated agarans with the A-units partially C-2 sulfated or 6-O-methoxylated presetting the B-units in the cyclized (3,6-anhydro-α-L-galactose) or in the non-cyclized form (α-L-galactose). The latter is significantly substituted by sulfate groups on C-6. In vitro and in vivo assays showed that this sulfated agaran inhibited hemolysis, coagulation, proteolysis, edema, and hemorrhage of L. muta venom. Neutralization of hemorrhagic activity was also observed when the agaran was administered by different routes and after or before the venom injection. Furthermore, the agaran blocked the edema caused by a phospholipase A2 isolated from the L. muta venom. Experimental evidence therefore indicates that the sulfated agaran of L. aldingensis has potential to aid antivenom therapy of accidents caused by L. muta venom and may help to develop more effective antivenom treatments of snake bites in general.

Structural characterization and gastroprotective property of a novel glucofructan from Allium ampeloprasum var. porrum.

A new polysaccharide with an estimated weight-average molar mass of 2.6×10(3) was isolated from Allium ampeloprasum var. porrum by hot water extraction, and purified by Sephacryl S-300 HR high-resolution chromatography. It was composed of D-fructose and D-glucose in 10:6 molar ratio, respectively. The structure of the glucofructan was investigated by chemical and spectroscopic methods, including methylation analysis, nuclear magnetic resonance, and electrospray mass spectrometry (ES-MS). The results permitted the structure of the glucofructan to be written as α-D-Glcp-(1→1)-ß-D-Fruf-(2→1)-{[α-D-Glcp-(1→6)-ß-D-Fruf-(2→6)]-ß-D-Fruf-(2→1)}4-ß-D-Fruf-(2↔1)-α-D-Glcp. Results of the present study indicated that this new glucofructan exhibited significant gastroprotective property, using in vivo experimental models.

Sulfated heterorhamnans from the green seaweed Gayralia oxysperma: partial depolymerization, chemical structure and antitumor activity.

Sulfated heterorhamnans produced by Gayralia oxysperma were utilized for the preparation of two homogeneous and highly sulfated Smith-degraded products (M(w) of 109 and 251 kDa), which were constituted principally by 3-linked α-L-rhamnosyl units 2- or 4-sulfate and 2-linked α-L-rhamnosyl units 4- or 3,4-sulfate, in different percentages. The homogeneous products and the crude extracts containing the sulfated heterorhamnans showed cytotoxic effect against U87MG cells. These sulfated polysaccharides induced an increase in the number of cells in G1 phase with concomitant increase of the mRNA levels of p53 and p21. The presence of 2-linked disulfated rhamnose residues together with the molecular weight could be important factors to be correlated with the inhibitory effect on human glioblastoma cells.

Polysaccharide isolated from Agardhiella ramosissima: chemical structure and anti-inflammation activity.

The sulfated polysaccharide (PLS) fraction of Agardhiella ramosissima was characterized by microanalysis, infrared spectroscopy, NMR and gas-liquid-chromatography-mass-spectrometry. The main constituent of PLS was the ι carrageenan. The monosaccharide composition of the PLS showed galactose, 3,6-anhydrogalactose and 6-O-methylgalactose. The PLS (30 mg kg(-1)) significantly reduced the paw oedema induced by carrageenan, dextran, histamine and serotonin and also was able to significantly inhibit leucocyte migration into the peritoneal cavity and decrease the concentration of myeloperoxidase (MPO) in paw tissue. In the antinociceptive tests, the pre-treatment with PLS reduced the number of writhes, the licking time but did not increase the latency time of response. This study demonstrates for the first time the anti-inflammatory and anti-nociceptive effects of PLS from A. ramosissima. Thus, we concluded that PLS could be a new natural tool in pain and acute inflammatory conditions.

Structure and anti-metapneumovirus activity of sulfated galactans from the red seaweed Cryptonemia seminervis.

The anti-HMPV (human metapneumovirus) activity was determined for sulfated dl-hybrid galactans obtained from the red seaweed Cryptonemia seminervis and their depolymerized products obtained by reductive partial hydrolysis. Structural studies carried out in three homogeneous depolymerized fractions DS-1, DS-2e and DS-3 (Mw of 51.6-63.8 kDa) showed that these galactans present different chemical characteristics, as monosaccharide composition, content of sulfate groups (14.1-29.9%) and agaran:carrageenan molar ratio diads, 2.7:1 for DS-1 and DS-2e and 1:1 for DS-3. The sulfate groups are located principally on C-2 of ß-d-galactopyranose and 4,6-O-(1'-carboxyethylidene)-ß-d-galactopyranose residues and on C-6 of α-galactose residues. Sulfated dl-galactans and their depolymerized products exhibited antiviral activity at a very early stage of the viral infection cycle. All fractions, except DS-2e inhibited HMPV replication by binding to the viral particle. Besides depolymerized galactans DS-2e and DS-3 inhibited the recognition of cell receptor by HMPV and penetration to the host cell, respectively.