Marine Drugs

2024

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18 pages, 7206 KiB

Open AccessArticle

Extraction Optimization and Anti-Tumor Activity of Polysaccharides from Chlamydomonas reinhardtii

by Zhongwen Liang, Lan Xiong, Ying Zang, Zhijuan Tang, Zhenyu Shang, Jingyu Zhang, Zihan Jia, Yanting Huang, Xiaoyu Ye, Hongquan Liu and Mei Li

Mar. Drugs 2024, 22(8), 356; https://doi.org/10.3390/md22080356 - 2 Aug 2024

Viewed by 906

Abstract

Chlamydomonas reinhardtii polysaccharides (CRPs) are bioactive compounds derived from C. reinhardtii, yet their potential in cancer therapy remains largely unexplored. This study optimized the ultrasound-assisted extraction conditions using response surface methodology and proceeded with the isolation and purification of these polysaccharides. The [...] Read more.

Chlamydomonas reinhardtii polysaccharides (CRPs) are bioactive compounds derived from C. reinhardtii, yet their potential in cancer therapy remains largely unexplored. This study optimized the ultrasound-assisted extraction conditions using response surface methodology and proceeded with the isolation and purification of these polysaccharides. The optimal extraction conditions were identified as a sodium hydroxide concentration of 1.5%, ultrasonic power of 200 W, a solid-to-liquid ratio of 1:25 g/mL, an ultrasonic treatment time of 10 min, and a water bath duration of 2.5 h, yielding an actual extraction rate of 5.71 ± 0.001%, which closely aligns with the predicted value of 5.639%. Infrared analysis revealed that CRP-1 and CRP-2 are α-pyranose structures containing furoic acid, while CRP-3 and CRP-4 are β-pyranose structures containing furoic acid. Experimental results demonstrated that all four purified polysaccharides inhibited the proliferation of cervical (HeLa) hepatoma (HepG-2) and colon (HCT-116) cancer cells, with CRP-4 showing the most significant inhibitory effect on colon cancer and cervical cancer, achieving inhibition rates of 60.58 ± 0.88% and 40.44 ± 1.44%, respectively, and significantly reducing the migration of HeLa cells. DAPI staining confirmed that the four purified polysaccharides inhibit cell proliferation and migration by inducing apoptosis in HeLa cells. CRP-1 has the most significant inhibitory effect on the proliferation of liver cancer cells. This study not only elucidates the potential application of C. reinhardtii polysaccharides in cancer therapy but also provides a scientific basis for their further development and utilization. Full article

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27 pages, 14164 KiB

Open AccessArticle

A Comparative Analysis of the Anti-Tumor Activity of Sixteen Polysaccharide Fractions from Three Large Brown Seaweed, Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida

by Lin Song, Yunze Niu, Ran Chen, Hao Ju, Zijian Liu, Bida Zhang, Wancui Xie and Yi Gao

Mar. Drugs 2024, 22(7), 316; https://doi.org/10.3390/md22070316 - 16 Jul 2024

Viewed by 784

Abstract

Searching for natural products with anti-tumor activity is an important aspect of cancer research. Seaweed polysaccharides from brown seaweed have shown promising anti-tumor activity; however, their structure, composition, and biological activity vary considerably, depending on many factors. In this study, 16 polysaccharide fractions [...] Read more.

Searching for natural products with anti-tumor activity is an important aspect of cancer research. Seaweed polysaccharides from brown seaweed have shown promising anti-tumor activity; however, their structure, composition, and biological activity vary considerably, depending on many factors. In this study, 16 polysaccharide fractions were extracted and purified from three large brown seaweed species (Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida). The chemical composition analysis revealed that the polysaccharide fractions have varying molecular weights ranging from 8.889 to 729.67 kDa, and sulfate contents ranging from 0.50% to 10.77%. Additionally, they exhibit different monosaccharide compositions and secondary structures. Subsequently, their anti-tumor activity was compared against five tumor cell lines (A549, B16, HeLa, HepG_2, and SH-SY5Y). The results showed that different fractions exhibited distinct anti-tumor properties against tumor cells. Flow cytometry and cytoplasmic fluorescence staining (Hoechst/AO staining) further confirmed that these effective fractions significantly induce tumor cell apoptosis without cytotoxicity. qRT-RCR results demonstrated that the polysaccharide fractions up-regulated the expression of Caspase-3, Caspase-8, Caspase-9, and Bax while down-regulating the expression of Bcl-2 and CDK-2. This study comprehensively compared the anti-tumor activity of polysaccharide fractions from large brown seaweed, providing valuable insights into the potent combinations of brown seaweed polysaccharides as anti-tumor agents. Full article

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2022

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18 pages, 4078 KiB

Open AccessArticle

Complexes of Cu–Polysaccharide of a Marine Red Microalga Produce Spikes with Antimicrobial Activity

by Nofar Yehuda, Levi A. Gheber, Ariel Kushmaro and Shoshana (Mails) Arad

Mar. Drugs 2022, 20(12), 787; https://doi.org/10.3390/md20120787 - 19 Dec 2022

Cited by 2 | Viewed by 3970

Abstract

Metal–polysaccharides have recently raised significant interest due to their multifunctional bioactivities. The antimicrobial activity of a complex of Cu₂O with the sulfated polysaccharide (PS) of the marine red microalga Porphyridium sp. was previously attributed to spikes formed on the complex surface [...] Read more.

Metal–polysaccharides have recently raised significant interest due to their multifunctional bioactivities. The antimicrobial activity of a complex of Cu₂O with the sulfated polysaccharide (PS) of the marine red microalga Porphyridium sp. was previously attributed to spikes formed on the complex surface (roughness). This hypothesis was further examined here using other Cu–PS complexes (i.e., monovalent-Cu₂O, CuCl and divalent-CuO, CuCl₂). The nanostructure parameters of the monovalent complexes, namely, longer spikes (1000 nm) and greater density (2000–5000 spikes/µm²) were found to be related to the superior inhibition of microbial growth and viability and biofilm formation. When Escherichia coli TV1061, used as a bioluminescent test organism, was exposed to the monovalent Cu–PS complexes, enhanced bioluminescence accumulation was observed, probably due to membrane perforation by the spikes on the surface of the complexes and consequent cytoplasmic leakage. In addition, differences were found in the surface chemistry of the monovalent and divalent Cu–PS complexes, with the monovalent Cu–PS complexes exhibiting greater stability (ζ-potential, FTIR spectra, and leaching out), which could be related to spike formation. This study thus supports our hypothesis that the spikes protruding from the monovalent Cu–PS surfaces, as characterized by their aspect ratio, are responsible for the antimicrobial and antibiofilm activities of the complexes. Full article

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11 pages, 6884 KiB

Open AccessArticle

Polysaccharide from Edible Alga Enteromorpha clathrata Improves Ulcerative Colitis in Association with Increased Abundance of Parabacteroides spp. in the Gut Microbiota of Dextran Sulfate Sodium-Fed Mice

by Mingfeng Ma, Tianyu Fu, Yamin Wang, Aijun Zhang, Puyue Gao, Qingsen Shang and Guangli Yu

Mar. Drugs 2022, 20(12), 764; https://doi.org/10.3390/md20120764 - 4 Dec 2022

Cited by 8 | Viewed by 2318

Abstract

Polysaccharide from the edible alga Enteromorpha clathrata has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we [...] Read more.

Polysaccharide from the edible alga Enteromorpha clathrata has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we illustrate that Enteromorpha clathrata polysaccharide (ECP) could alleviate body weight loss, reduce incidences of colonic bleeding, improve stool consistency and ameliorate mucosal damage in diseased mice. 16S rRNA high-throughput sequencing and bioinformatic analysis indicated that ECP significantly changed the structure of the gut microbiota and increased the abundance of Parabacteroides spp. in DSS-fed mice. In vitro fermentation studies further confirmed that ECP could promote the growth of Parabacteroides distasonis F1-28, a next-generation probiotic bacterium isolated from the human gut, and increase its production of short-chain fatty acids. Additionally, Parabacteroides distasonis F1-28 was also found to have anti-ulcerative colitis effects in DSS-fed mice. Altogether, our study demonstrates for the first time a beneficial effect of ECP on ulcerative colitis and provides a possible basis for understanding its therapeutic mechanisms from the perspective of symbiotic gut bacteria Parabacteroides distasonis. Full article

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Dietary ECP improved ulcerative colitis in DSS-fed mice. Changes of the body weight during the experiment (A). Representative morphologies of the colon (B). Colon length (C). Symptom score analysis of ulcerative colitis (D). * p < 0.05 versus NC group; ** p < 0.01 versus NC group; # p < 0.05 versus MD group; ## p < 0.01 versus MD group. Full article ">Figure 2
Dietary ECP ameliorated DSS-induced mucosal damage in the colon. H&E staining (A) and Alcian blue staining (B) of the colon tissues. Alcian blue staining was applied to show the changes of the intestinal acidic mucin O-glycans. Histopathological colon score analysis (C). ** p < 0.01 versus NC group; # p < 0.05 versus MD group. Full article ">Figure 3
Dietary ECP changed the overall structure of the gut microbiota in diseased mice. Venn diagram analysis of the OTUs (A). PCA score plot analysis (B). NMDS score plot analysis (C). Full article ">Figure 4
Dietary ECP modulated the composition of the gut microbiota at different taxonomic levels. Heatmap analysis of the gut microbiota at the phylum and genus levels. Full article ">Figure 5
LEfSe LDA score analysis of the gut microbiota in NC versus MD group (A) and MD versus ECP group (B). Only bacterial taxa with an LDA score of above 4.0 and 3.0 are listed. Full article ">Figure 6
ECP promoted the growth of P. distasonis F1-28 and increased the production of SCFAs. Growth curves (A) and colony forming units (CFUs) (B). Concentrations of total SCFAs (C), acetate (D), propionate (E) and succinate (F). * p < 0.05 versus NC group; ** p < 0.01 versus NC group. Full article ">Figure 7
Oral administration of live P. distasonis F1-28 alleviated ulcerative colitis in DSS-fed mice. Changes of the body weight during the experiment (A). Representative morphologies of the colon (B). Colon length (C). Symptom score analysis of ulcerative colitis (D). ** p < 0.01 versus NC group; # p < 0.05 versus MD group; ## p < 0.01 versus MD group. Full article ">Figure 8
Oral administration of live P. distasonis F1-28 attenuated DSS-induced mucosal damage in the colon. H&E staining (A) and Alcian blue staining (B) of the colon tissues. Histopathological colon score analysis (C). ** p < 0.01 versus NC group; ## p < 0.01 versus MD group. Full article ">

22 pages, 6555 KiB

Open AccessArticle

Anti-Biofilm Activity of a Hyaluronan-like Exopolysaccharide from the Marine Vibrio MO245 against Pathogenic Bacteria

by Marie Champion, Emilie Portier, Karine Vallée-Réhel, Isabelle Linossier, Eric Balnois, Guillaume Vignaud, Xavier Moppert, Claire Hellio and Fabienne Faÿ

Mar. Drugs 2022, 20(11), 728; https://doi.org/10.3390/md20110728 - 21 Nov 2022

Cited by 7 | Viewed by 2430

Abstract

Biofilms, responsible for many serious drawbacks in the medical and marine environment, can grow on abiotic and biotic surfaces. Commercial anti-biofilm solutions, based on the use of biocides, are available but their use increases the risk of antibiotic resistance and environmental pollution in [...] Read more.

Biofilms, responsible for many serious drawbacks in the medical and marine environment, can grow on abiotic and biotic surfaces. Commercial anti-biofilm solutions, based on the use of biocides, are available but their use increases the risk of antibiotic resistance and environmental pollution in marine industries. There is an urgent need to work on the development of ecofriendly solutions, formulated without biocidal agents, that rely on the anti-adhesive physico-chemical properties of their materials. In this context, exopolysaccharides (EPSs) are natural biopolymers with complex properties than may be used as anti-adhesive agents. This study is focused on the effect of the EPS MO245, a hyaluronic acid-like polysaccharide, on the growth, adhesion, biofilm maturation, and dispersion of two pathogenic model strains, Pseudomonas aeruginosa sp. PaO1 and Vibrio harveyi DSM19623. Our results demonstrated that MO245 may limit biofilm formation, with a biofilm inhibition between 20 and 50%, without any biocidal activity. Since EPSs have no significant impact on the bacterial motility and quorum sensing factors, our results indicate that physico-chemical interactions between the bacteria and the surfaces are modified due to the presence of an adsorbed EPS layer acting as a non-adsorbing layer. Full article

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18 pages, 2621 KiB

Open AccessArticle

Neoagaro-Oligosaccharides Ameliorate Chronic Restraint Stress-Induced Depression by Increasing 5-HT and BDNF in the Brain and Remodeling the Gut Microbiota of Mice

by Yan Zhuang, Runying Zeng, Xiao Liu, Longhe Yang and Zhuhua Chan

Mar. Drugs 2022, 20(11), 725; https://doi.org/10.3390/md20110725 - 18 Nov 2022

Cited by 10 | Viewed by 3128

Abstract

Neoagaro-oligosaccharides (NAOs) belong to the algae oligosaccharides. NAOs have been found to have diverse biological activities. However, the effects of NAOs on depression and their underlying mechanism have not been thoroughly studied. A chronic restraint stress (CRS)-induced C57BL/6J mouse model was used to [...] Read more.

Neoagaro-oligosaccharides (NAOs) belong to the algae oligosaccharides. NAOs have been found to have diverse biological activities. However, the effects of NAOs on depression and their underlying mechanism have not been thoroughly studied. A chronic restraint stress (CRS)-induced C57BL/6J mouse model was used to assess the antidepressant effects of NAOs. Anxiety and depression behaviors were assessed by open field tests (OFT) and forced swimming tests (FST), while interleukin 18 (IL-18), 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were the molecular biomarkers of depression. Fecal microbiota transplantation (FMT) was performed. The results showed that NAO treatment significantly improved the body weight of depressed mice and reduced the central area time in the OFT and immobility time in the FST. NAO treatment decreased the levels of IL-18 in the serum and increased the levels of 5-HT in the serum and whole brain and of BDNF in the whole brain. NAO treatment mitigated the gut microbiota dysbiosis in the depressed mice and reversed the decreased levels of short-chain fatty acids (SCFAs) in the cecum of the depressed mice. FMT indicated that the gut microbiota is, indeed, linked to depression, which was reflected in the changes in weight gain and behaviors. In a word, NAOs effectively reversed the CRS-induced mice model of depression, which depended on the changes in the gut microbiota and SCFAs, as well as its modulation of 5-HT and BDNF. Full article

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14 pages, 2582 KiB

Open AccessArticle

In Vivo Anticoagulant and Antithrombic Activity of Depolymerized Glycosaminoglycan from Apostichopus japonicus and Dynamic Effect–Exposure Relationship in Rat Plasma

by Han Wang, Dandan He, Linlin Duan, Lv Lv, Qun Gao, Yuanhong Wang, Shuang Yang and Zhihua Lv

Mar. Drugs 2022, 20(10), 631; https://doi.org/10.3390/md20100631 - 2 Oct 2022

Cited by 2 | Viewed by 2638

Abstract

Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and [...] Read more.

Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa). These glycosaminoglycans markedly prevented thrombosis formation and thrombin-induced platelet aggregation in a dose- and molecular weight-dependent manner in vitro and in vivo. The further bleeding time measurement indicated that DAHG10 exhibited obviously lower hemorrhage risks than native AHG100. Following oral administration, DAHG10 could be absorbed into blood, further dose-dependently prolonging activated partial thromboplastin time (APTT) and thrombin time (TT) as well as inhibiting FXa and FIIa partially through FXase. Anticoagulant activity was positively associated with plasma concentration following oral administration of DAHG10. Our study proposed a new point of view to understand the correlation between effects and exposure of fucosylated chondroitin sulfate as an effective and safe oral antithrombotic agent. Full article

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The structure of AHG100. Full article ">Figure 2
1H NMR and IR spectrum of AHG100 and DAHGs. (A) 1H NMR spectrum, (B) IR spectrum. Full article ">Figure 3
The structural information and anticoagulant activity of AHG100 and DAHGs (mean ± SD, n = 3). (A) Anti-FIIa activity, (B) anti-FXa activity, (C) anti-intrinsic FXase complex activity, and (D) platelet aggregation. Compared with normal control (NC) group, * p < 0.05, ** p < 0.01. Full article ">Figure 4
Effects of AHG100 and DAHGs on CT and BT (mean ± SD, n = 10). (A) CT, (B) BT. Compared with NC group * p < 0.05, ** p < 0.01. Full article ">Figure 5
Effects of AHG100 and DAHGs on antithrombosis (mean ± SD, n = 8). (A) Thrombus formation time, (B) thrombus length, and (C) thrombus weight. Compared with NC group ** p < 0.01. Full article ">Figure 6
Effect of AHG100 and DAHGs on APTT and TT in rats (mean ± SD, n = 3). (A) AHG100, APTT; (B) AHG100, TT; (C) DAHG50, APTT; (D) DAHG50, TT; (E) DAHG10, APTT; (F) DAHG10, TT. Compared with blank time of intravenous administration, * p < 0.05, ** p < 0.01. Compared with blank time of oral administration, # p < 0.05. Full article ">Figure 7
Effect of DAHG10 on FXa, FIIa, and FXIIa in rats (mean ± SD, n = 4). (A) Residual activity of FIIa after oral dosing with DAHG10. (B) Residual activity of FIIa after injection of DAHG10. (C) Residual activity of FXa after oral dosing with DAHG10. (D) Residual activity of FXa after injection of DAHG10. (E) Residual activity of factor XIIa (FXIIa) after oral dosing with DAHG10. (F) Residual activity of FXIIa after injection of DAHG10. Compared with blank time after administration, # p < 0.05, ## p < 0.01, ### p < 0.01. Full article ">Figure 8
The concentration–time–effect relationship in rats (mean ± SD, n = 4). (A) Inhibition of FIIa activity after oral administration of DAHG10 at 250 mg/kg. (B) Inhibition of FIIa activity after intravenous injection of DAHG10 at 5 mg/kg [<a href="#B22-marinedrugs-20-00631" class="html-bibr">22</a>]. (C) Inhibition of FXa activity after oral administration of DAHG10 at 250 mg/kg. (D) Inhibition of FXa activity after intravenous injection of DAHG10 at 5 mg/kg [<a href="#B22-marinedrugs-20-00631" class="html-bibr">22</a>]. Full article ">

16 pages, 4370 KiB

Open AccessArticle

Synthesis, Characterization, and the Antioxidant Activity of Phenolic Acid Chitooligosaccharide Derivatives

by Yan Sun, Xia Ji, Jingmin Cui, Yingqi Mi, Jingjing Zhang and Zhanyong Guo

Mar. Drugs 2022, 20(8), 489; https://doi.org/10.3390/md20080489 - 28 Jul 2022

Cited by 18 | Viewed by 2221

Abstract

A series of phenolic acid chitooligosaccharide (COS) derivatives synthesized by two mild and green methods were illuminated in this paper. Seven phenolic acids were selected to combine two kinds of COS derivatives: the phenolic acid chitooligosaccharide salt derivatives and the phenolic-acid-acylated chitooligosaccharide derivatives. [...] Read more.

A series of phenolic acid chitooligosaccharide (COS) derivatives synthesized by two mild and green methods were illuminated in this paper. Seven phenolic acids were selected to combine two kinds of COS derivatives: the phenolic acid chitooligosaccharide salt derivatives and the phenolic-acid-acylated chitooligosaccharide derivatives. The structures of the derivatives were characterized by FT-IR and ¹H NMR spectra. The antioxidant experiment results in vitro (including DPPH-radical scavenging activity, superoxide-radical scavenging activity, hydroxyl-radical scavenging ability, and reducing power) demonstrated that the derivatives exhibited significantly enhanced antioxidant activity compared to COS. Moreover, the study showed that the phenolic acid chitooligosaccharide salts had stronger antioxidant activity than phenolic-acid-acylated chitooligosaccharide. The cytotoxicity assay of L929 cells in vitro indicated that the derivatives had low cytotoxicity and good biocompatibility. In conclusion, this study provides a possible synthetic method for developing novel and nontoxic antioxidant agents which can be used in the food and cosmetics industry. Full article

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20 pages, 3981 KiB

Open AccessArticle

Immunomodulatory Activity In Vitro and In Vivo of a Sulfated Polysaccharide with Novel Structure from the Green Alga Ulvaconglobata Kjellman

by Sujian Cao, Yajing Yang, Shan Liu, Zhuling Shao, Xiao Chu and Wenjun Mao

Mar. Drugs 2022, 20(7), 447; https://doi.org/10.3390/md20070447 - 8 Jul 2022

Cited by 10 | Viewed by 2723

Abstract

Algae accumulate large amounts of polysaccharides in their cell walls or intercellular regions. Polysaccharides from algae possess high potential as promising candidates for marine drug development. In this study, a sulfated polysaccharide, UCP, from the green alga Ulva conglobata Kjellman was obtained by [...] Read more.

Algae accumulate large amounts of polysaccharides in their cell walls or intercellular regions. Polysaccharides from algae possess high potential as promising candidates for marine drug development. In this study, a sulfated polysaccharide, UCP, from the green alga Ulva conglobata Kjellman was obtained by water extraction, anion-exchange, and size-exclusion chromatography purification, and its structure was characterized by a combination of chemical and spectroscopic methods. UCP mainly consisted of →4)-α/β-l-Rhap-(1→, →4)-β-d-Xylp-(1→ and →4)-β-d-GlcAp-(1→ residues. Sulfate ester groups were substituted mainly at C-3 of →4)-l-Rhap-(1→ and C-2 of →4)-β-d-Xylp-(1→. Partial glycosylation was at C-2 of →4)-α-l-Rhap-(1→ residues. UCP possessed a potent immunomodulatory effect in vitro, evaluated by the assays of lymphocyte proliferation and macrophage phagocytosis. The immunomodulatory activity of UCP in vivo was further investigated using immunosuppressive mice induced by cyclophosphamide. The results showed that UCP markedly increased the spleen and thymus indexes and ameliorated the cyclophosphamide-induced damage to the spleen and thymus. UCP could increase the levels of white blood cells, lymphocytes, and platelets, and improve the hematopoietic inhibition caused by cyclophosphamide. Moreover, UCP significantly promoted the secretions of the immunoglobulin (Ig)G, IgE, and IgM. The data demonstrated that UCP is a novel sulfated polysaccharide and may be a promising immunomodulatory agent. Full article

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18 pages, 2839 KiB

Open AccessArticle

Stimulating the Hematopoietic Effect of Simulated Digestive Product of Fucoidan from Sargassum fusiforme on Cyclophosphamide-Induced Hematopoietic Damage in Mice and Its Protective Mechanisms Based on Serum Lipidomics

by Wei-Ping Ma, Shi-Ning Yin, Jia-Peng Chen, Xi-Cheng Geng, Ming-Fei Liu, Hai-Hua Li, Ming Liu and Hong-Bing Liu

Mar. Drugs 2022, 20(3), 201; https://doi.org/10.3390/md20030201 - 9 Mar 2022

Cited by 7 | Viewed by 2967

Abstract

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and [...] Read more.

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8–7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25–100 μg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide. Full article

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Graphical abstract

Graphical abstract
Full article ">Figure 1
Effects of simulated digestive product of fucoidan from Sargassum fusiforme (DSFF) on the (A) body weight gain, (B) splenic index, and (C) thymic index of mice with cyclophosphamide-induced hematopoietic damage. ** p < 0.01, vs. control; # p < 0.05, ## p < 0.01, vs. model. Full article ">Figure 2
Effects of DSFF on bone marrow DNA content in cyclophosphamide-induced mice. Data are the mean ± standard deviation (n = 10). ** p < 0.01, vs. control; ## p < 0.01, vs. model. Full article ">Figure 3
PCA score plots of serum samples: (A) control vs. model in positive ion mode; (B) control vs. model in negative ion mode; (C) control vs. model vs. rhG-CSF in positive ion mode; (D) control vs. model vs. rhG-CSF in negative ion mode. Full article ">Figure 4
OPLS-DA score plot of serum samples from control group and model group in (A) positive ion mode and (B) negative ion mode. Full article ">Figure 5
Differential metabolite pathway analysis of serum samples in the control group and the model group. A: arachidonic acid metabolism; B: glycerophospholipid metabolism; C: alpha-linolenic acid metabolism; D: linoleic acid metabolism. Full article ">Figure 6
PCA and OPLS-DA score plots of serum samples between the control group, model group, and 3.6 μg/mL DSFF group under positive ion mode. (A): PCA score plot; (B): OPLS-DA score plot. Full article ">Figure 7
Effects of simulated digestive product of fucoidan from Sargassum fusiforme (DSFF) on the proliferation and differentiation of K562 cells. (A) Proliferative effect of DSFF on K562 cells using CCK-8 assay; (B) effects of DSFF on the differentiation of K562 cells using a benzidine-staining assay (10×, scale bar: 100 μm); (C) effects of DSFF on the erythroid differentiation of K562 cells using flow cytometry; (D) effects of DSFF on the megakaryocyte differentiation of K562 cells using flow cytometry; (E) effects of DSFF on the differentiation-related protein expression of K562 cells using Western blotting. Data are the mean ± standard deviation (n = 10). * p < 0.05, ** p < 0.01, vs. control. Full article ">

2021

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24 pages, 4568 KiB

Open AccessArticle

Agarose Stearate-Carbomer₉₄₀ as Stabilizer and Rheology Modifier for Surfactant-Free Cosmetic Formulations

by Qiong Xiao, Guo Chen, Yong-Hui Zhang, Fu-Quan Chen, Hui-Fen Weng and An-Feng Xiao

Mar. Drugs 2021, 19(6), 344; https://doi.org/10.3390/md19060344 - 16 Jun 2021

Cited by 16 | Viewed by 3536

Abstract

Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional, high-performance polymers are good alternatives to overcome these problems. In this study, agarose stearate (AS) with emulsifying, thickening, and gel properties was synthesized. Surfactant-free cosmetic [...] Read more.

Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional, high-performance polymers are good alternatives to overcome these problems. In this study, agarose stearate (AS) with emulsifying, thickening, and gel properties was synthesized. Surfactant-free cosmetic formulations were successfully prepared from AS and carbomer₉₄₀ (CBM₉₄₀) mixed systems. The correlation of rheological parameter with skin feeling was determined to study the usability of the mixed systems in cosmetics. Based on rheological analysis, the surfactant-free cosmetic cream (SFC) stabilized by AS-carbomer₉₄₀ showed shear-thinning behavior and strongly synergistic action. The SFC exhibited a gel-like behavior and had rheological properties similar to commercial cosmetic creams. Scanning electron microscope images proved that the AS-CBM₉₄₀ network played an important role in SFC’s stability. Oil content could reinforce the elastic characteristics of the AS-CBM₉₄₀ matrix. The SFCs showed a good appearance and sensation during and after rubbing into skin. The knowledge gained from this study may be useful for designing surfactant-free cosmetic cream with rheological properties that can be tailored for particular commercial cosmetic applications. They may also be useful for producing medicine products with highly viscous or gel-like textures, such as some ointments and wound dressings. Full article

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2020

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14 pages, 4128 KiB

Open AccessArticle

Isolation, Characterization and Bioactive Properties of Alkali-Extracted Polysaccharides from Enteromorpha prolifera

by Shifeng Zhao, Yuan He, Chungu Wang, Israa Assani, Peilei Hou, Yan Feng, Juanjuan Yang, Yehua Wang, Zhixin Liao and Songdong Shen

Mar. Drugs 2020, 18(11), 552; https://doi.org/10.3390/md18110552 - 6 Nov 2020

Cited by 23 | Viewed by 2973

Abstract

Four new purified polysaccharides (PAP) were isolated and purified from the Enteromorpha prolifera by alkali extraction, and further characterization was investigated. Their average molecular weights of PAP-1, PAP-2, PAP-3, and PAP-4 were estimated as 3.44 × 10⁴, 6.42 × 10⁴ [...] Read more.

Four new purified polysaccharides (PAP) were isolated and purified from the Enteromorpha prolifera by alkali extraction, and further characterization was investigated. Their average molecular weights of PAP-1, PAP-2, PAP-3, and PAP-4 were estimated as 3.44 × 10⁴, 6.42 × 10⁴, 1.20 × 10⁵, and 4.82 × 10⁴ Da, respectively. The results from monosaccharide analysis indicated that PAP-1, PAP-2, PAP-3 were acidic polysaccharides and PAP-4 was a neutral polysaccharide. PAP-1 and PAP-2 mainly consist of galacturonic acid, while PAP-3 and PAP-4 mainly contained rhamnose. Congo red test showed that no triple helical structure was detected in the four polysaccharides. The antioxidant activities were investigated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), Superoxide, and 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical assay. In vitro antitumor activities were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PAP-1 exhibited relatively stronger antioxidant activities among the four polysaccharides in a dose-dependent manner. At a concentration of 1.00 mg/mL, the antioxidant activities of PAP-1 on the DPPH radical scavenging rate, superoxide anion radical scavenging rate, and ABTS radical rate at 1.00 mg/mL were 56.40%, 54.27%, and 42.07%, respectively. They also showed no significant inhibitory activity against MGC-803, HepG2, T24, and Bel-7402 cells. These investigations of polysaccharides provide a scientific basis for the use of E. prolifera as an ingredient in functional foods and medicines. Full article

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13 pages, 3091 KiB

Open AccessArticle

Sargassum fusiforme Polysaccharides Prevent High-Fat Diet-Induced Early Fasting Hypoglycemia and Regulate the Gut Microbiota Composition

by Bin Wei, Qi-Wu Zhong, Song-Ze Ke, Tao-Shun Zhou, Qiao-Li Xu, Si-Jia Wang, Jian-Wei Chen, Hua-Wei Zhang, Wei-Hua Jin and Hong Wang

Mar. Drugs 2020, 18(9), 444; https://doi.org/10.3390/md18090444 - 27 Aug 2020

Cited by 19 | Viewed by 3411

Abstract

A low fasting blood glucose level is a common symptom in diabetes patients and can be induced by high-fat diet (HFD) feeding at an early stage, which may play important roles in the development of diabetes, but has received little attention. In this [...] Read more.

A low fasting blood glucose level is a common symptom in diabetes patients and can be induced by high-fat diet (HFD) feeding at an early stage, which may play important roles in the development of diabetes, but has received little attention. In this study, five polysaccharides were prepared from Sargassumfusiforme and their effects on HFD-induced fasting hypoglycemia and gut microbiota dysbiosis were investigated. The results indicated that C57BL/6J male mice fed an HFD for 4 weeks developed severe hypoglycemia and four Sargassumfusiforme polysaccharides (SFPs), consisting of Sf-2, Sf-3, Sf-3-1, and Sf-A, significantly prevented early fasting hypoglycemia without inducing hyperglycemia. Sf-1 and Sf-A could also significantly prevent HFD-induced weight gain. Sf-2, Sf-3, Sf-3-1, and Sf-A mainly attenuated the HFD-induced decrease in Bacteroidetes, and all five SFPs had a considerable influence on the relative abundance of Oscillospira, Mucispirillum, and Clostridiales. Correlation analysis revealed that the fasting blood glucose level was associated with the relative abundance of Mucispinllum and Oscillospira. Receiver operating characteristic analysis indicated that Mucispinllum and Oscillospira exhibited good discriminatory power (AUC = 0.745–0.833) in the prediction of fasting hypoglycemia. Our findings highlight the novel application of SFPs (especially Sf-A) in glucose homeostasis and the potential roles of Mucispinllum and Oscillospira in the biological activity of SFPs. Full article

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Effects of S. fusiforme polysaccharides on the (A) body weight, (B) fasting blood glucose, (C) oral glucose tolerance test (OGTT), (D) liver, (E) epididymal fat, and (F) pancreas weight in high-fat diet (HFD)-treated mice. Values are the mean ± SD (n = 10). * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. blank. # p < 0.05, ## p < 0.01, and ### p < 0.001 vs. control. Full article ">Figure 2
Effects of S. fusiforme polysaccharides on the composition and α-diversity of the gut microbiota in HFD-treated mice. (A) Gut microbiota composition at the phylum level, (B) Abundance-based Coverage Estimator (ACE) metric, (C) Chao1 diversity index, (D) Simpson’s diversity index, and (E) Shannon’s diversity index of the gut microbiota. Values are the mean ± SD (n = 10). *** p < 0.001 vs. blank. # p < 0.05 vs. control. Full article ">Figure 3
Effects of S. fusiforme polysaccharides on the relative abundance of (A) Bacteroidetes, (B) Firmicutes, (C) Proteobacteria, (D) Actinobacteria, (E) Deferribacteres, and (F) Verrucomicrobia in the gut microbiota in HFD-treated mice. Values are the mean ± SD (n = 10). * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. blank. # p < 0.05, ### p < 0.001 vs. control. Full article ">Figure 4
Effects of S. fusiforme polysaccharides on the relative abundance of (A) o_Clostridiales._._, (B) g_Oscillospira, (C) g_Mucispirillum, (D) f_Coriobacteriaceae.g_, (E) g_Moryella, and (F) g_Bifidobacterium in the gut microbiota in HFD-treated mice. Values are the mean ± SD (n = 10). * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. blank. # p < 0.05, ## p < 0.01, and ### p < 0.001 vs. control. Full article ">Figure 5
Effects of S. fusiforme polysaccharides on the (A) gut microbiota composition at the genus level, (B) predicted functional gene, (C) metabolic pathway coverage, and (D) abundance in HFD-treated mice. Full article ">Figure 6
(A) Correlations between the fasting blood glucose level and the relative abundance of gut microbiota. A color key is shown at the bottom right of the heatmap to demonstrate the size of the correlation coefficient. Values in each lattice represent the correlation coefficients. * False discovery rate (FDR)-corrected p-value < 0.05; ** FDR-corrected p-value < 0.01; *** FDR-corrected p-value < 0.05. NA, not applicable. (B) Fitting receiver operating characteristic (ROC) curves of g_Oscillospira, g_Bifidobacterium, f_Coriobacteriaceae.g_, and g_Mucispinllum for the prediction of fasting hypoglycemia. Full article ">

16 pages, 4520 KiB

Open AccessArticle

Immunomodulatory Effects of N-Acetyl Chitooligosaccharides on RAW264.7 Macrophages

by Jun-Jin Deng, Zong-Qiu Li, Ze-Quan Mo, Shun Xu, He-Hua Mao, Dan Shi, Zhi-Wei Li, Xue-Ming Dan and Xiao-Chun Luo

Mar. Drugs 2020, 18(8), 421; https://doi.org/10.3390/md18080421 - 12 Aug 2020

Cited by 35 | Viewed by 4426

Abstract

The ongoing development of new production methods may lead to the commercialization of N-acetyl chitooligosaccharides (NACOS), such as chitosan oligosaccharides (COS). The bioactivity of NACOS, although not well detailed, differs from that of COS, as they have more acetyl groups than COS. [...] Read more.

The ongoing development of new production methods may lead to the commercialization of N-acetyl chitooligosaccharides (NACOS), such as chitosan oligosaccharides (COS). The bioactivity of NACOS, although not well detailed, differs from that of COS, as they have more acetyl groups than COS. We used two enzymatically produced NACOS with different molecular compositions and six NACOS (NACOS1–6) with a single degree of polymerization to verify their immunomodulatory effects on the RAW264.7 macrophage cell line. We aimed to identify any differences between COS and various NACOS with a single degree of polymerization. The results showed that NACOS had similar immune enhancement effects on RAW264.7 cells as COS, including the generation of reactive oxygen species (ROS), phagocytotic activity, and the production of pro-inflammation cytokines (IL-1β, IL-6, and TNF-α). However, unlike COS and lipopolysaccharide (LPS), NACOS1 and NACOS6 significantly inhibited nitric oxide (NO) production. Besides their immune enhancement effects, NACOS also significantly inhibited the LPS-induced RAW264.7 inflammatory response with some differences between various polymerization degrees. We confirmed that the NF-κB pathway is associated with the immunomodulatory effects of NACOS on RAW264.7 cells. This study could inform the application of NACOS with varying different degrees of polymerization in human health. Full article

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26 pages, 1315 KiB

Open AccessReview

Potential Beneficial Actions of Fucoidan in Brain and Liver Injury, Disease, and Intoxication—Potential Implication of Sirtuins

by Jasmina Dimitrova-Shumkovska, Ljupcho Krstanoski and Leo Veenman

Mar. Drugs 2020, 18(5), 242; https://doi.org/10.3390/md18050242 - 5 May 2020

Cited by 37 | Viewed by 6590

Abstract

Increased interest in natural antioxidants has brought to light the fucoidans (sulfated polysaccharides present in brown marine algae) as highly valued nutrients as well as effective and safe therapeutics against several diseases. Based on their satisfactory in vitro antioxidant potency, researchers have identified [...] Read more.

Increased interest in natural antioxidants has brought to light the fucoidans (sulfated polysaccharides present in brown marine algae) as highly valued nutrients as well as effective and safe therapeutics against several diseases. Based on their satisfactory in vitro antioxidant potency, researchers have identified this molecule as an efficient remedy for neuropathological as well as metabolic disorders. Some of this therapeutic activity is accomplished by upregulation of cytoprotective molecular pathways capable of restoring the enzymatic antioxidant activity and normal mitochondrial functions. Sirtuin-3 has been discovered as a key player for achieving the neuroprotective role of fucoidan by managing these pathways, whose ultimate goal is retrieving the entirety of the antioxidant response and preventing apoptosis of neurons, thereby averting neurodegeneration and brain injuries. Another pathway whereby fucoidan exerts neuroprotective capabilities is by interactions with P-selectin on endothelial cells, thereby preventing macrophages from entering the brain proper. Furthermore, beneficial influences of fucoidan have been established in hepatocytes after xenobiotic induced liver injury by decreasing transaminase leakage and autophagy as well as obtaining optimal levels of intracellular fiber, which ultimately prevents fibrosis. The hepatoprotective role of this marine polysaccharide also includes a sirtuin, namely sirtuin-1 overexpression, which alleviates obesity and insulin resistance through suppression of hyperglycemia, reducing inflammation and stimulation of enzymatic antioxidant response. While fucoidan is very effective in animal models for brain injury and neuronal degeneration, in general, it is accepted that fucoidan shows somewhat limited potency in liver. Thus far, it has been used in large doses for treatment of acute liver injuries. Thus, it appears that further optimization of fucoidan derivatives may establish enhanced versatility for treatments of various disorders, in addition to brain injury and disease. Full article

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Mechanism of action of fucoidan in traumatic brain injury (TBI). Fucoidan alleviates brain injury through upregulation of sirtuin, which decreases reactive oxygen species (ROS) overproduction by inhibiting the mitochondrial permeability transition pore (mPTP) opening, and restores normal mitochondrial function via stimulation of ATP synthesis, and attenuates mitochondria-initiated apoptosis by decreasing leakage of cytochrome c from the mitochondria into the cytosol. Additionally, fucoidan stimulates expression of FOXO3A and Nrf-2-ARE genes, thus increasing glutathione (GSH) production and Mn-SOD and Cat activity. Full article ">Figure 2
Effects of fucoidan on brain disease. Fucoidan reduces inflammatory response in brain diseases by inhibiting microglial activation, thus resulting in significantly decreased neuronal and astrocyte degeneration due to diminishing production of pro-apoptotic agents and improving antioxidant responses of the cell. Furthermore, fucoidan prevents leukocyte adhesion to the brain by blocking P-selectin. Full article ">Figure 3
Effects of fucoidan on liver injury. Damaging agents at the top left side, APAP and carbon tetrachloride (CCl4), and protective fucoidan at the top right side. Fucoidan averts liver fibrosis by inhibiting HSCs production through optimal synthesis of collagen and alpha smooth muscle actin and prevents tissue damage by reducing transaminase release and restoring antioxidant potentials of cells. It decreases CYP2E1 activity, which reduces levels of toxic metabolites and inhibits TGF-β/Smad pathway, thereby hindering the occurrence of autophagosomes. Fucoidan also stimulates expression of sirtuin-1 in the liver, which activates AMPK and alleviates insulin resistance. Full article ">

14 pages, 1935 KiB

Open AccessArticle

Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway

by Wenhui Jin, Longhe Yang, Zhiwei Yi, Hua Fang, Weizhu Chen, Zhuan Hong, Yiping Zhang, Guangya Zhang and Long Li

Mar. Drugs 2020, 18(4), 222; https://doi.org/10.3390/md18040222 - 21 Apr 2020

Cited by 23 | Viewed by 4344

Abstract

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a [...] Read more.

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA–PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway. Full article

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13 pages, 1892 KiB

Open AccessArticle

Identification of a Key Enzyme for the Hydrolysis of β-(1→3)-Xylosyl Linkage in Red Alga Dulse Xylooligosaccharide from Bifidobacterium Adolescentis

by Manami Kobayashi, Yuya Kumagai, Yohei Yamamoto, Hajime Yasui and Hideki Kishimura

Mar. Drugs 2020, 18(3), 174; https://doi.org/10.3390/md18030174 - 20 Mar 2020

Cited by 21 | Viewed by 4308

Abstract

Red alga dulse possesses a unique xylan, which is composed of a linear β-(1→3)/β-(1→4)-xylosyl linkage. We previously prepared characteristic xylooligosaccharide (DX3, (β-(1→3)-xylosyl-xylobiose)) from dulse. In this study, we evaluated the prebiotic effect of DX3 on enteric bacterium. Although DX3 was utilized by Bacteroides [...] Read more.

Red alga dulse possesses a unique xylan, which is composed of a linear β-(1→3)/β-(1→4)-xylosyl linkage. We previously prepared characteristic xylooligosaccharide (DX3, (β-(1→3)-xylosyl-xylobiose)) from dulse. In this study, we evaluated the prebiotic effect of DX3 on enteric bacterium. Although DX3 was utilized by Bacteroides sp. and Bifidobacterium adolescentis, Bacteroides Ksp. grew slowly as compared with β-(1→4)-xylotriose (X3) but B. adolescentis grew similar to X3. Therefore, we aimed to find the key DX3 hydrolysis enzymes in B. adolescentis. From bioinformatics analysis, two enzymes from the glycoside hydrolase family 43 (BAD0423: subfamily 12 and BAD0428: subfamily 11) were selected and expressed in Escherichia coli. BAD0423 hydrolyzed β-(1→3)-xylosyl linkage in DX3 with the specific activity of 2988 mU/mg producing xylose (X1) and xylobiose (X2), and showed low activity on X2 and X3. BAD0428 showed high activity on X2 and X3 producing X1, and the activity of BAD0428 on DX3 was 1298 mU/mg producing X1. Cooperative hydrolysis of DX3 was found in the combination of BAD0423 and BAD0428 producing X1 as the main product. From enzymatic character, hydrolysis of X3 was completed by one enzyme BAD0428, whereas hydrolysis of DX3 needed more than two enzymes. Full article

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Effect of carbohydrate on bacterial growth and pH. The bacterial strains were cultured at 37 °C for 96 h in PYF (Peptone−Yeast extract−Fildes) medium containing 0.5% carbohydrate samples under anaerobic conditions. The data were obtained as ΔOD600 and ΔpH by the subtraction of each bacterial growth without carbohydrate samples. Error bars indicate SD (n = 3). Growth data of C. paraputrificum and E. limosum for β-(1→4)-xylotriose (X3) were not determined. Symbols: black bar, glucose; gray bar, xylose; red bar, X3; and blue bar, β-(1→3)/β-(1→4)-xylotriose (DX3). Full article ">Figure 2
Time course growth rate of B. vulgatus (a) and B. adolescentis (b). Bacteria grow in PYF medium containing 0.5% carbohydrates at 37 °C in anaerobic condition. Symbols: ●, glucose (G1); ◯, xylose (X1); ▲, X3; △, DX3. Mean ± standard deviation of three replicate determinations and the error bars were within the symbols. Full article ">Figure 3
Relationship between bacteria and the number of enzymes containing β-xylosidase (EC 3.2.1.37) in glycoside hydrolase families (GHs). The colors are related to the number of enzymes from pink (low) to red (high). The bold and underlined number means that GHs contain β-xylosidase. Full article ">Figure 4
Relationship between bacteria and the number of enzymes in the GH43 subfamily. The colors are related to the number of enzymes from pink (low) to purple (high). The bold and underlined number shows subfamilies contain β-xylosidase. Full article ">Figure 5
Hydrolysis products of oligosaccharides (XOS). Ten mM XOS was hydrolyzed by 50 μg/mL BAD0423, BAD0428, and BAD1527 at pH 6.5 and 37 °C for 1 h. The products were analyzed by HPLC. Black and gray indicate the amount of X1 and X2, respectively. Full article ">Figure 6
The putative hydrolysis mechanism of DX3 and X3. (a) DX3; (b) X3. Full article ">

29 pages, 2151 KiB

Open AccessReview

Advanced Technologies for the Extraction of Marine Brown Algal Polysaccharides

by Ana Dobrinčić, Sandra Balbino, Zoran Zorić, Sandra Pedisić, Danijela Bursać Kovačević, Ivona Elez Garofulić and Verica Dragović-Uzelac

Mar. Drugs 2020, 18(3), 168; https://doi.org/10.3390/md18030168 - 18 Mar 2020

Cited by 154 | Viewed by 11590

Abstract

Over the years, brown algae bioactive polysaccharides laminarin, alginate and fucoidan have been isolated and used in functional foods, cosmeceutical and pharmaceutical industries. The extraction process of these polysaccharides includes several complex and time-consuming steps and the correct adjustment of extraction parameters (e.g., [...] Read more.

Over the years, brown algae bioactive polysaccharides laminarin, alginate and fucoidan have been isolated and used in functional foods, cosmeceutical and pharmaceutical industries. The extraction process of these polysaccharides includes several complex and time-consuming steps and the correct adjustment of extraction parameters (e.g., time, temperature, power, pressure, solvent and sample to solvent ratio) greatly influences the yield, physical, chemical and biochemical properties as well as their biological activities. This review includes the most recent conventional procedures for brown algae polysaccharides extraction along with advanced extraction techniques (microwave-assisted extraction, ultrasound assisted extraction, pressurized liquid extraction and enzymes assisted extraction) which can effectively improve extraction process. The influence of these extraction techniques and their individual parameters on yield, chemical structure and biological activities from the most current literature is discussed, along with their potential for commercial applications as bioactive compounds and drug delivery systems. Full article

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26 pages, 1286 KiB

Open AccessReview

Advances in Research on the Bioactivity of Alginate Oligosaccharides

by Maochen Xing, Qi Cao, Yu Wang, Han Xiao, Jiarui Zhao, Qing Zhang, Aiguo Ji and Shuliang Song

Mar. Drugs 2020, 18(3), 144; https://doi.org/10.3390/md18030144 - 28 Feb 2020

Cited by 153 | Viewed by 9055

Abstract

Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely [...] Read more.

Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products. Full article

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13 pages, 4649 KiB

Open AccessArticle

Impact of Prevalence Ratios of Chondroitin Sulfate (CS)- 4 and -6 Isomers Derived from Marine Sources in Cell Proliferation and Chondrogenic Differentiation Processes

by Estefanía López-Senra, Paula Casal-Beiroa, Miriam López-Álvarez, Julia Serra, Pío González, Jesus Valcarcel, José Antonio Vázquez, Elena F. Burguera, Francisco J. Blanco and Joana Magalhães

Mar. Drugs 2020, 18(2), 94; https://doi.org/10.3390/md18020094 - 31 Jan 2020

Cited by 17 | Viewed by 4544

Abstract

Osteoarthritis is the most prevalent rheumatic disease. During disease progression, differences have been described in the prevalence of chondroitin sulfate (CS) isomers. Marine derived-CS present a higher proportion of the 6S isomer, offering therapeutic potential. Accordingly, we evaluated the effect of exogenous supplementation [...] Read more.

Osteoarthritis is the most prevalent rheumatic disease. During disease progression, differences have been described in the prevalence of chondroitin sulfate (CS) isomers. Marine derived-CS present a higher proportion of the 6S isomer, offering therapeutic potential. Accordingly, we evaluated the effect of exogenous supplementation of CS, derived from the small spotted catshark (Scyliorhinus canicula), blue shark (Prionace glauca), thornback skate (Raja clavata) and bovine CS (reference), on the proliferation of osteochondral cell lines (MG-63 and T/C-28a2) and the chondrogenic differentiation of mesenchymal stromal cells (MSCs). MG-G3 proliferation was comparable between R. clavata (CS-6 intermediate ratio) and bovine CS (CS-4 enrichment), for concentrations below 0.5 mg/mL, defined as a toxicity threshold. T/C-28a2 proliferation was significantly improved by intermediate ratios of CS-6 and -4 isomers (S. canicula and R. clavata). A dose-dependent response was observed for S. canicula (200 µg/mL vs 50 and 10 µg/mL) and bovine CS (200 and 100 µg/mL vs 10 µg/mL). CS sulfation patterns discretely affected MSCs chondrogenesis; even though S. canicula and R. clavata CS up-regulated chondrogenic markers expression (aggrecan and collagen type II) these were not statistically significant. We demonstrate that intermediate values of CS-4 and -6 isomers improve cell proliferation and offer potential for chondrogenic promotion, although more studies are needed to elucidate its mechanism of action. Full article

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MG-63 osteoblast cell line proliferation (MTT assay), after 72 h incubation in minimum essential medium-Eagle with Earle’s balanced salt solution (EMEM) supplemented with different concentrations of chondroitin sulfate (CS) (50 µg/mL, 100 µg/mL, 0.5 mg/mL, 1 mg/mL and 10 mg/mL), from fish (Prionace glauca, Raja clavata and Scyliorhinus canicula) and bovine sources, normalized against CS-free condition which was assigned the value of 1. Significant statistical differences for p < 0.05 (*) are shown. Full article ">Figure 2
T/C-28a2 chondrocytic cell line viability and proliferation (directly proportional to alamar blue dye reduction) after 24, 48 and 72 h incubation in basal medium (Dulbecco’s modified Eagle’s medium (DMEM) 10%) supplemented with different concentrations of CS (10 µg/mL, 50 µg/mL, 100 µg/mL and 200 µg/mL) or CS-free, derived from fish (Prionace glauca, Raja clavata and Scyliorhinus canicula) and bovine sources. Significant statistical differences for p < 0.05 (*) and p < 0.01 (**) are shown. No significant differences were found amongst the different CS sources and CS-free condition. Full article ">Figure 3
Histological analysis for morphology (haematoxylin and eosin, HE), proteoglycans (toluidine blue, TB) and sulfated glycosaminoglycans (GAGs) synthesis (safranin-O, SO), and immunolocalization of collagen-type II (Col-II) and aggrecan (scale bar = 200 µm), was performed in osteoarthritic bone marrow mesenchymal stromal cells (BM-MSCs) pellets, after 14 days, in chondrogenic medium supplemented with 100 µg/mL CS extracted from fish (Prionace glauca, Raja clavata and Scyliorhinus canicula) and bovine sources or CS-free. Immunopositive aggrecan (bottom, left) and collagen type-II (bottom, right) percentage area were normalized against cell-pellets total area (n = 3). Full article ">Figure 4
mRNA relative expression of SOX9, ACAN, COL2A1, COL1A1, COL10A1 and IL6 from osteoarthritic BM-MSCs pellets, after 14 days, in chondrogenic medium supplemented with 100 µg/mL CS extracted from fish (Prionace glauca, Raja clavata and Scyliorhinus canicula) and bovine sources. Data were normalized against chondrogenic medium in the absence of CS (CS-free) condition (positive control for chondrogenesis), represented as n = 1. Values are given as the mean of 4 donors with standard deviation. No significant differences were found. Full article ">

16 pages, 7952 KiB

Open AccessArticle

Pre-Treatment with Laminarin Protects Hippocampal CA1 Pyramidal Neurons and Attenuates Reactive Gliosis Following Transient Forebrain Ischemia in Gerbils

by Tae-Kyeong Lee, Ji Hyeon Ahn, Cheol Woo Park, Bora Kim, Young Eun Park, Jae-Chul Lee, Joon Ha Park, Go Eun Yang, Myoung Cheol Shin, Jun Hwi Cho, Il-Jun Kang and Moo-Ho Won

Mar. Drugs 2020, 18(1), 52; https://doi.org/10.3390/md18010052 - 12 Jan 2020

Cited by 23 | Viewed by 3651

Abstract

Transient brain ischemia triggers selective neuronal death/loss, especially in vulnerable regions of the brain including the hippocampus. Laminarin, a polysaccharide originating from brown seaweed, has various pharmaceutical properties including an antioxidant function. To the best of our knowledge, few studies have been conducted [...] Read more.

Transient brain ischemia triggers selective neuronal death/loss, especially in vulnerable regions of the brain including the hippocampus. Laminarin, a polysaccharide originating from brown seaweed, has various pharmaceutical properties including an antioxidant function. To the best of our knowledge, few studies have been conducted on the protective effects of laminarin against ischemic injury induced by ischemic insults. In this study, we histopathologically investigated the neuroprotective effects of laminarin in the Cornu Ammonis 1 (CA1) field of the hippocampus, which is very vulnerable to ischemia-reperfusion injury, following transient forebrain ischemia (TFI) for five minutes in gerbils. The neuroprotective effect was examined by cresyl violet staining, Fluoro-Jade B histofluorescence staining and immunohistochemistry for neuronal-specific nuclear protein. Additionally, to study gliosis (glial changes), we performed immunohistochemistry for glial fibrillary acidic protein to examine astrocytes, and ionized calcium-binding adaptor molecule 1 to examine microglia. Furthermore, we examined alterations in pro-inflammatory M1 microglia by using double immunofluorescence. Pretreatment with 10 mg/kg laminarin failed to protect neurons in the hippocampal CA1 field and did not attenuate reactive gliosis in the field following TFI. In contrast, pretreatment with 50 or 100 mg/kg laminarin protected neurons, attenuated reactive gliosis and reduced pro-inflammatory M1 microglia in the CA1 field following TFI. Based on these results, we firmly propose that 50 mg/kg laminarin can be strategically applied to develop a preventative against injuries following cerebral ischemic insults. Full article

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15 pages, 4412 KiB

Open AccessArticle

Fucoidan from Undaria pinnatifida Ameliorates Epidermal Barrier Disruption via Keratinocyte Differentiation and CaSR Level Regulation

by Yu Chen, Xuenan Li, Xiaoshuang Gan, Junmei Qi, Biao Che, Meiling Tai, Shuang Gao, Wengang Zhao, Nuo Xu and Zhenlin Hu

Mar. Drugs 2019, 17(12), 660; https://doi.org/10.3390/md17120660 - 24 Nov 2019

Cited by 10 | Viewed by 3942

Abstract

The epidermal barrier acts as a line of defense against external agents as well as helps to maintain body homeostasis. The calcium concentration gradient across the epidermal barrier is closely related to the proliferation and differentiation of keratinocytes (KCs), and the regulation of [...] Read more.

The epidermal barrier acts as a line of defense against external agents as well as helps to maintain body homeostasis. The calcium concentration gradient across the epidermal barrier is closely related to the proliferation and differentiation of keratinocytes (KCs), and the regulation of these two processes is the key to the repair of epidermal barrier disruption. In the present study, we found that fucoidan from Undaria pinnatifida (UPF) could promote the repair of epidermal barrier disruption in mice. The mechanistic study demonstrated that UPF could promote HaCaT cell differentiation under low calcium condition by up-regulating the expression of calcium-sensing receptor (CaSR), which could then lead to the activation of the Catenin/PLCγ1 pathway. Further, UPF could increase the expression of CaSR through activate the ERK and p38 pathway. These findings reveal the molecular mechanism of UPF in the repair of the epidermal barrier and provide a basis for the development of UPF into an agent for the repair of epidermal barrier repair. Full article

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Molecular weight and monosaccharide composition of UPF. (A) The molecular weight and molecular mass distributions of UPF were determined by GPC-MALLS consisting of a refractive index detector Waters 2414 (RI) and a Wyatt DAWN EOS MALLS detector (B) The UPF were dissolved in ammonia, mixed with PMP, and neutralized with 200 µL of formic acid. The derivatization chromatomap was collected by UPLC/Q-TOF-MS. (C) Derivatization chromatomap of standard monosaccharides (Man, Rib, Rha, GluUA, GalUA, Glc, Gal, Xyl, Ara, Fuc). Full article ">Figure 2
The effect of UPF on the recovery of epidermal barrier. Epidermal barrier disruption of ICR mice was induced by tape stripping on their shaved back skin until the TEWL reached 40 mg/cm2/hour. UPF hydrogel was administrated topically on the dorsal skin. (A) The photos were taken every 12 h after disruption. (B) The values of TEWL were measured at 0 h, 12 h, 24 h, 48 h, 72 h, 84 h. Data are presented as means ± SEM obtained from three independent experiments, * p < 0.05 and ** p < 0.01 versus the vehicle control. (C) The back skin were harvested at 84 h and the skin sections were prepared and stained with hematoxylin–eosin. (D) The back skin were harvested at 84 h and the skin sections were prepared and stained with immunohistochemistry. Full article ">Figure 3
The effect of UPF on proliferation, differentiation and sustained Ca2+ concentration in HaCaT cells. HaCaT cells were treated with or without indicated concentrations (10, 20, 50 μg/mL of UPF. (A) The involucrin and filaggrin mRNA levels in HaCaT cells were assayed after 72 h treatment by qPCR. (B) The involucrin and filaggrin proteins levels in HaCaT cells were assayed after 72 h treatment by Western blot. (C) The involucrin and filaggrin mRNA levels in NHEK cells were assayed after 72 h treatment by qPCR. (D) The involucrin and filaggrin proteins levels in NHEK cells were assayed after 72 h treatment by Western blot. (E) The proliferation of HaCaT cells were assayed after 24 h, 48 h or 72 h treatment by BrdU assay. (F) HaCaT cells were treated with or without indicated concentrations (10, 20, 50 µg/mL) of UPF for 24 h, loaded with Fura-4 AM, and the fluorescence was recorded using a confocal microscope. Data are presented as means ± SEM obtained from three independent experiments, * p < 0.05 and ** p < 0.01 versus Control. Full article ">Figure 4
The effect of UPF on the expression of CaSR and CaSR mediated signaling pathway. (A) HaCaT cells were treated with or without indicated concentrations (10, 20, 50 µg/mL) of UPF, the CaSR mRNA levels in HaCaT cells were assayed at 12 h, 24 h, and 48 h by qPCR. (B) HaCaT cells were treated with or without indicated concentrations (10, 20, 50 µg/mL) of UPF, the CaSR protein levels in HaCaT cells were assayed at 12 h, 24 h, and 48 h by Western blot. (C) CaSR mediated signaling pathway. (D) HaCaT cells were treated with or without indicated concentrations (10, 20, 50 µg/mL) of UPF, the levels of PLC-γ1, p120-catenin, phospho-PLCγ1 and phospho- p120-catenin in cytoplasm and β-catenin in the nucleus were detected by Western blot. (E) HaCaT cells were exposed to indicate concentrations of UPF with or without NPS-2143 (CaSR inhibitor, 150 nM), the protein levels of PLC-γ1, p120-catenin, phospho-PLCγ1, phospho-p120-catenin, the involucrin and filaggrin were assayed by Western blot. (F) HaCaT cells were exposed to indicate concentrations of UPF with or without NPS-2143 (CaSR inhibitor) for 72 h, the involucrin and filaggrin mRNA levels were assayed by qPCR. Full article ">Figure 5
UPF increases the expression of CaSR via the ERK and p38 signaling pathway. (A) HaCaT cells were treated with or without indicated concentrations (10, 20, 50 μg/mL) of UPF, the levels of ERK, p38, phospho-ERK and phospho-p38 in cells were detected by Western blotting. (B) HaCaT cells were exposed to indicated concentrations of UPF with or without LY3214996 (ERK inhibitor, 100 nM) and SB203580 (p38 inhibitor, 20 µM) for 12 h, the levels of PLC-γ1, p120-catenin, phospho-PLCγ1 and phospho-p120-catenin in cells were detected by Western blotting. (C) The relative expression levels of phosphorylation of PLCγ1 and p120-catenin were detected by gray analysis. (D) HaCaT cells were exposed to indicated concentrations of UPF with or without LY3214996 and SB203580 for 72 h, the CaSR mRNA levels in HaCaT cells were assayed by qPCR. (E) HaCaT cells were exposed to indicated concentrations of UPF with or without LY3214996 and SB203580 for 72 h, the involucrin and filaggrin mRNA levels in HaCaT cells were assayed by qPCR. Full article ">

12 pages, 1899 KiB

Open AccessArticle

Effect of Carboxymethylation and Phosphorylation on the Properties of Polysaccharides from Sepia esculenta Ink: Antioxidation and Anticoagulation in Vitro

by Huazhong Liu, Fangping Li and Ping Luo

Mar. Drugs 2019, 17(11), 626; https://doi.org/10.3390/md17110626 - 1 Nov 2019

Cited by 28 | Viewed by 2964

Abstract

To investigate the effect of carboxymethylation and phosphorylation modification on Sepia esculenta ink polysaccharide (SIP) properties, this study prepared carboxymethyl SIP (CSIP) with the chloracetic acid method, and phosphorylated SIP (PSIP) with the sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) method, on the basis of [...] Read more.

To investigate the effect of carboxymethylation and phosphorylation modification on Sepia esculenta ink polysaccharide (SIP) properties, this study prepared carboxymethyl SIP (CSIP) with the chloracetic acid method, and phosphorylated SIP (PSIP) with the sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) method, on the basis of an orthogonal experiment. The in vitro antioxidant and anticoagulant activities of the derivatives were determined by assessing the scavenging capacity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals, which activated the partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results showed that SIP was modified successfully to be CSIP and PSIP, and degrees of substitution (DSs) of the two products were 0.9913 and 0.0828, respectively. Phosphorylation efficiently improved the antioxidant property of SIP, and the IC₅₀ values of PSIP on DPPH and hydroxyl radicals decreased by 63.25% and 13.77%, respectively. But carboxymethylation reduced antioxidant activity of the native polysaccharide, IC₅₀ values of CSIP on the DPPH and hydroxyl radicals increased by 16.74% and 6.89%, respectively. SIP significantly prolonged the APTT, PT, and TT in a dose-dependent fashion, suggesting that SIP played an anticoagulant action through intrinsic, extrinsic, and common coagulation pathways. CSIP and PSIP both possessed a stronger anticoagulant capacity than SIP via the same pathways; moreover, CSIP was observed to be more effective in prolonging APTT and PT than PSIP. Full article

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Graphical abstract

Graphical abstract
Full article ">Figure 1
Effect of different reaction conditions on degree of substitution (DS) of carboxymethylated Sepia esculenta ink polysaccharides (CSIP). Under the scheduled different reaction conditions, the SIP was carboxymethylated by chloroacetic acid. The degree of substitution of CSIP was determined by the neutralization titration method and calculation according to the formula. Full article ">Figure 2
IR spectra of SIP and CSIP. IR spectra of the SIP and CSIP were recorded with KBr pellets on a Bruker Tensor 27 Fourier infrared spectrophotometer between 400–4000 cm−1. Full article ">Figure 3
Effect of different reaction conditions on the content of phosphate in phosphorylated SIP (PSIP). Under the scheduled different reaction conditions, the SIP was phosphorylated with the STMP/STPP method. The content of phosphate in PSIP was determined according to the equation, which was subjected to calculating the degree of substitution of PSIP. Full article ">Figure 4
IR spectra of SIP and PSIP. The IR spectra of SIP and PSIP were recorded with KBr pellets on a BRUKER TENSOR 27 Fourier infrared spectrophotometer between 400–4000 cm−1. Full article ">Figure 5
In vitro antioxidant activity of SIP, CSIP, and PSIP. The antioxidant capacity of SIP and its derivatives was assessed by the scavenging activities of DPPH and hydroxyl radicals. Full article ">Figure 6
In vitro anticoagulant property of SIP, CSIP, and PSIP. The anticoagulant capacity of SIP and its derivatives was assessed by determining the clotting time, including the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Different capital or lowercase letters express significant differences among various dosages (0, 6.25, 12.5, 25, 50, and 100) of polysaccharide (SIP, CSIP, or PSIP), ABCDE p < 0.01 or abcdef p < 0.05. Asterisk, * or **, means p < 0.05 or p < 0.01 between the same dosage of SIP and modified SIP (CSIP or PSIP), respectively. # or ## represent the difference, p < 0.05 or p < 0.01, between the same dosage of CSIP and PSIP, respectively. Full article ">Figure 6 Cont.
In vitro anticoagulant property of SIP, CSIP, and PSIP. The anticoagulant capacity of SIP and its derivatives was assessed by determining the clotting time, including the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Different capital or lowercase letters express significant differences among various dosages (0, 6.25, 12.5, 25, 50, and 100) of polysaccharide (SIP, CSIP, or PSIP), ABCDE p < 0.01 or abcdef p < 0.05. Asterisk, * or **, means p < 0.05 or p < 0.01 between the same dosage of SIP and modified SIP (CSIP or PSIP), respectively. # or ## represent the difference, p < 0.05 or p < 0.01, between the same dosage of CSIP and PSIP, respectively. Full article ">

14 pages, 3132 KiB

Open AccessArticle

Anti-Inflammatory and Anti-Aging Evaluation of Pigment–Protein Complex Extracted from Chlorella Pyrenoidosa

by Ruilin Zhang, Jian Chen, Xinwu Mao, Ping Qi and Xuewu Zhang

Mar. Drugs 2019, 17(10), 586; https://doi.org/10.3390/md17100586 - 16 Oct 2019

Cited by 23 | Viewed by 5472

Abstract

Oxidative stress contributes to chronic inflammatory processes implicated in aging, referred to as “inflamm-aging.” In this study, the potential anti-inflammatory and anti-aging effects of a pigment–protein complex (PPC) from Chlorella pyrenoidosa were investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and D-galactose (D-gal)-induced aging [...] Read more.

Oxidative stress contributes to chronic inflammatory processes implicated in aging, referred to as “inflamm-aging.” In this study, the potential anti-inflammatory and anti-aging effects of a pigment–protein complex (PPC) from Chlorella pyrenoidosa were investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and D-galactose (D-gal)-induced aging in a murine model. Results indicated that PPC inhibits the production of the inflammatory cytokines TNF-α and IL-6, and the inflammatory mediator nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. It also protected mice from D-gal induced informatory aging by increasing the activity of the antioxidant enzyme, such as superoxide dismutase (SOD), inhibiting D-gal-induced NF-κB upregulation, and increasing PPARs expression in the brain and gut. The findings indicated that PPC has favorable anti-inflammatory and anti-aging properties, and could be useful in the treatment of acute inflammation and senescence diseases. Full article

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Figure 1
Purification and characterization of the pigment–protein mixture from Chlorella pyrenoidosa. (a) Sephadex G-25 gel filtration chromatography; (b) Absorption spectrum of the pigment–protein complex (PPC); (c) HPLC analysis. Full article ">Figure 2
Effect of PPC on RAW 264.7 cells. (a) The viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The control group consisted of untreated cells and was considered as 100% of viable cells. Results were expressed as a percentage of viable cells when compared with the control group. (b) Nitric oxide (NO) production levels; (c) Expression levels of tumor necrosis factor (TNF)-α; (d) The levels of interleukin (IL)-6 production; (e) The levels of IL-10 production; (f) Phagocytosis rate. All the experiments were performed in triplicate. Duncan’s new multiple range test was performed to determine the significance differences. The values are expressed as the as mean ± SD. # p < 0.05 vs. the blank group, ## p < 0.01 vs. the blank group, * p < 0.05 vs. the LPS group, and ** p < 0.05 vs. the lipopolysaccharide (LPS) group. Full article ">Figure 3
D-galactose (D-gal) induced KMB17 cells premature senescence in vitro. (A) Cells morphology changes: normal group (a), Model group D-gal-stimulated (b), Ascorbic acid group (c), 200 μg/mL PPC (d), 400 μg/mL PPC (e); (B) The effects of PPC on KMB17 cell viability. The experiments were performed in triplicate, and the values are expressed as the as mean ± SD. Results were expressed as a percentage of viable cells when compared with the control group. Full article ">Figure 4
Effect of PPC on superoxide dismutase (SOD), malondialdehyde (MDA), NO, IL-6, TNF-α levels, and the morphological features of gut in D-gal-induced mice. (a) Changes in MDA, (b) SOD, and (c) NO production levels; (d) The levels of IL-6 production; (e) Expression levels of TNF-α; (f) The morphological features of hematoxylin and eosin (H&E) stained gut sections, Scale bar = 50 μm. A one-way ANOVA was performed to compare the three experimental groups. All the data are mean ± SD of three independent experiments. # p < 0.05 vs. the control group, ## p < 0.01 vs. the control group, * p < 0.05 vs. the model group, and ** p < 0.01 vs. the model group. Full article ">Figure 4 Cont.
Effect of PPC on superoxide dismutase (SOD), malondialdehyde (MDA), NO, IL-6, TNF-α levels, and the morphological features of gut in D-gal-induced mice. (a) Changes in MDA, (b) SOD, and (c) NO production levels; (d) The levels of IL-6 production; (e) Expression levels of TNF-α; (f) The morphological features of hematoxylin and eosin (H&E) stained gut sections, Scale bar = 50 μm. A one-way ANOVA was performed to compare the three experimental groups. All the data are mean ± SD of three independent experiments. # p < 0.05 vs. the control group, ## p < 0.01 vs. the control group, * p < 0.05 vs. the model group, and ** p < 0.01 vs. the model group. Full article ">Figure 5
(a) Effects of PPC on the expression levels of nuclear factor κB (NF-κB), PPARα, PPARγ, and p53 in mice, the proteins of brain and gut in each group were processed by Western blotting, and all data performed in triplicate; (b) Potential regulation pathways by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software (<a href="http://string.embl.de/);" target="_blank">http://string.embl.de/);</a> (c) Proposed mechanism of action on brain and intestine. Full article ">

17 pages, 3723 KiB

Open AccessArticle

Efficiently Anti-Obesity Effects of Unsaturated Alginate Oligosaccharides (UAOS) in High-Fat Diet (HFD)-Fed Mice

by Shangyong Li, Ningning He and Linna Wang

Mar. Drugs 2019, 17(9), 540; https://doi.org/10.3390/md17090540 - 17 Sep 2019

Cited by 59 | Viewed by 4680

Abstract

Obesity and its related complications have become one of the leading problems affecting human health. However, current anti-obesity treatments are limited by high cost and numerous adverse effects. In this study, we investigated the use of a non-toxic green food additive, known as [...] Read more.

Obesity and its related complications have become one of the leading problems affecting human health. However, current anti-obesity treatments are limited by high cost and numerous adverse effects. In this study, we investigated the use of a non-toxic green food additive, known as unsaturated alginate oligosaccharides (UAOS) from the enzymatic degradation of Laminaria japonicais, which showed effective anti-obesity effects in a high-fat diet (HFD) mouse model. Compared with acid hydrolyzed saturated alginate oligosaccharides (SAOS), UAOS significantly reduced body weight, serum lipid, including triacylglycerol (TG), total cholesterol (TC) and free fatty acids (FFA), liver weight, liver TG and TC, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, adipose mass, reactive oxygen species (ROS) formation, and accumulation induced in HFD mice. Moreover, the structural differences in β-d-mannuronate (M) and its C5 epimer α-l-guluronate (G) did not cause significant functional differences. Meanwhile, UAOS significantly increased both AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC) phosphorylation in adipocytes, which indicated that UAOS had an anti-obesity effect mainly through AMPK signaling. Our results indicate that UAOS has the potential for further development as an adjuvant treatment for many metabolic diseases such as fatty liver, hypertriglyceridemia, and possibly diabetes. Full article

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Scheme (A), TLC analysis (B), SE-HPLC analysis (C,D), and ESI-MS analysis (E,F) of UAOS and SAOS. Full article ">Figure 2
Changes in body weight on AOS treatment. Changes in body weight of treatment of UAOS (A) and SAOS (B), body weight gain (C) for 4 weeks. The data are represented as means ± standard deviation (SD, n = 6). Changes in the energy intake (D), body weight (E), body weight gain (F), and Lee’s index (G) during the eight-week treatment are shown. The body weight was recorded weekly. The data are represented as means ± standard deviation (SD, n = 12). Compare with HFD group, * p < 0.05, ** p < 0.01, *** p < 0.001. Compare with indicated groups, # p < 0.05. Full article ">Figure 3
Changes of AOS treatment on serum lipid. TG levels (A), TC levels (B), HDL-c levels (C), LDL-c levels (D), and FFA levels (E). The data are represented as means ± standard deviation (SD, n = 12). Compare with the HFD group, * p < 0.05, ** p < 0.01, *** p < 0.001. Compare with indicated groups, # p < 0.05, ## p < 0.01. Full article ">Figure 4
Changes of AOS treatment on the hepatic lipid. The whole liver weight (A), liver TC (B), and TG (C) are displayed. The whole liver morphology (D) and H&E staining for liver tissue (E) (200×) are shown. The concentration of serum AST (F) and ALT (G) are also shown. The data are represented as means ± standard deviation (SD, n = 12). Compare with the HFD group, * p < 0.05, ** p < 0.01, *** p < 0.001. Compare with indicated groups, # p < 0.05. Full article ">Figure 5
Changes of UAOS treatment on adipocytes in adipose mass. The fat mass of epididymal (A), mesenteric (B), perirenal tissues (C), adipocyte size (D), the whole WAT (E), and WAT tissue stained by H&E staining (200×) (F) are shown in the figure. The data are represented as means ± standard deviation (SD, n = 12). Compare with the HFD group, * p < 0.05, ** p < 0.01, *** p < 0.001. Compare with indicated groups, # p < 0.05, ## p < 0.01. Full article ">Figure 6
The effect of AOS treatment on hepatic H2O2 level (A) and liver MDA level (B) in mice fed a high fat diet for 8 weeks. The data are represented as means ± standard deviation (SD, n = 12). Compare with the HFD group, * p < 0.05, ** p < 0.01, *** p < 0.001. Compare with indicated groups, # p < 0.05, ## p < 0.01. Full article ">Figure 7
UAOS activated the AMPK signaling pathway in WAT. (A) The protein expression level of AMPK, p-AMPK, ACC, and p-ACC in WAT were detected by Western blotting. (B) The relative protein levels were quantified. (C) The proposed mechanism by which AOS causes effects of hepatoprotection and anti-obesity. The data are represented as means ± standard deviation (SD, n = 3). * p < 0.05, ** p < 0.01, *** p < 0.001. Full article ">

18 pages, 1998 KiB

Open AccessArticle

In-Depth Characterization of Bioactive Extracts from Posidonia oceanica Waste Biomass

by Isaac Benito-González, Amparo López-Rubio, Antonio Martínez-Abad, Ana-Rosa Ballester, Irene Falcó, Luis González-Candelas, Gloria Sánchez, Jesús Lozano-Sánchez, Isabel Borrás-Linares, Antonio Segura-Carretero and Marta Martínez-Sanz

Mar. Drugs 2019, 17(7), 409; https://doi.org/10.3390/md17070409 - 9 Jul 2019

Cited by 23 | Viewed by 5519

Abstract

Posidonia oceanica waste biomass has been valorised to produce extracts by means of different methodologies and their bioactive properties have been evaluated. Water-based extracts were produced using ultrasound-assisted and hot water methods and classified according to their ethanol-affinity (E1: ethanol soluble; E2: non-soluble). [...] Read more.

Posidonia oceanica waste biomass has been valorised to produce extracts by means of different methodologies and their bioactive properties have been evaluated. Water-based extracts were produced using ultrasound-assisted and hot water methods and classified according to their ethanol-affinity (E1: ethanol soluble; E2: non-soluble). Moreover, a conventional protocol with organic solvents was applied, yielding E3 extracts. Compositional and structural characterization confirmed that while E1 and E3 extracts were mainly composed of minerals and lipids, respectively, E2 extracts were a mixture of minerals, proteins and carbohydrates. All the extracts showed remarkably high antioxidant capacity, which was not only related to phenolic compounds but also to the presence of proteins and polysaccharides. All E2 and E3 extracts inhibited the growth of several foodborne fungi, while only E3 extracts decreased substantially the infectivity of feline calicivirus and murine norovirus. These results show the potential of P. oceanica waste biomass for the production of bioactive extracts. Full article

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Figure 1
Carbohydrate composition of the aqueous P. oceanica extracts. (A) Absolute concentration values for E1 and E2 extracts and (B) their relative abundance in the E2 extracts. Different letters denote significant monosaccharide content differences between extracts (p ≤ 0.05). Full article ">Figure 2
FT-IR spectra of the different P. oceanica extracts obtained by means of water-based extractions (A,B) and organic solvent-based extractions (C). E1 US, E2 US and E3 US spectra have been offset for clarity. Full article ">Figure 3
XRD patterns of the freeze-dried extracts. (A,B) Water-soluble extracts and (C) organic-soluble extracts. The spectra from E1 US and E2 US have been offset for clarity. Full article ">Figure 4
Reduction of (A) feline calicivirus (FCV) titres (log TCID50/mL) and (B) murine norovirus (MNV) titres (log TCID50/mL) treated with P. oceanica extracts at different concentrations (0.5 or 0.05%) after 25 °C and 37 °C ON incubations, respectively. * Each bar represents the average of triplicates. Within each column, different letters denote significant differences between treatments. ** Horizontal line depicts the detection limit. Full article ">

12 pages, 734 KiB

Open AccessCommunication

Different Antifungal Activity of Anabaena sp., Ecklonia sp., and Jania sp. against Botrytis cinerea

by Hillary Righini, Elena Baraldi, Yolanda García Fernández, Antera Martel Quintana and Roberta Roberti

Mar. Drugs 2019, 17(5), 299; https://doi.org/10.3390/md17050299 - 20 May 2019

Cited by 32 | Viewed by 4638

Abstract

Water extracts and polysaccharides from Anabaena sp., Ecklonia sp., and Jania sp. were tested for their activity against the fungal plant pathogen Botrytis cinerea. Water extracts at 2.5, 5.0, and 10.0 mg/mL inhibited B. cinerea growth in vitro. Antifungal activity of polysaccharides [...] Read more.

Water extracts and polysaccharides from Anabaena sp., Ecklonia sp., and Jania sp. were tested for their activity against the fungal plant pathogen Botrytis cinerea. Water extracts at 2.5, 5.0, and 10.0 mg/mL inhibited B. cinerea growth in vitro. Antifungal activity of polysaccharides obtained by N-cetylpyridinium bromide precipitation in water extracts was evaluated in vitro and in vitro at 0.5, 2.0, and 3.5 mg/mL. These concentrations were tested against fungal colony growth, spore germination, colony forming units (CFUs), CFU growth, and on strawberry fruits against B. cinerea infection with pre- and post-harvest application. In in vitro experiments, polysaccharides from Anabaena sp. and from Ecklonia sp. inhibited B. cinerea colony growth, CFUs, and CFU growth, while those extracted from Jania sp. reduced only the pathogen spore germination. In in vitro experiments, all concentrations of polysaccharides from Anabaena sp., Ecklonia sp., and Jania sp. reduced both the strawberry fruits infected area and the pathogen sporulation in the pre-harvest treatment, suggesting that they might be good candidates as preventive products in crop protection. Full article

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Figure 1
Effect of different POL concentrations on Botrytis cinerea colony growth rate. Treatment and dose factors and their interaction are significant, according to factorial ANOVA. F(2,36) = 18.2, p < 0.0001 (for treatment factor), F(3,36) = 27.8, p < 0.0001 (for dose factor), F(6,36) = 2.7, p < 0.05 (for interaction). Columns are mean values ± SD. The same uppercase letter within each POL treatment and the same lowercase letter among concentrations indicates no significant differences according to Student–Newman–Keuls test (p < 0.05). Full article ">Figure 2
Infected area of strawberry fruit caused by Botrytis cinerea (a) and its sporulation (b) after pre-harvest treatment with different concentrations of polysaccharides from Anabaena sp. (AN), Ecklonia sp. (ECK), and Jania sp. (JAN). Polysaccharides and concentration factors and their interaction are significant, according to factorial ANOVA. (a) F(2,240) = 270.0, p < 0.0001 (for treatment factor), F(3,240) = 266.3, p < 0.0001 (for dose factor), F(6,240) = 45.0, p < 0.05 (for interaction). (b) F(2,96) = 23.0, p < 0.0001 (for treatment factor), F(3,96) = 370.0, p < 0.0001 (for dose factor), F(6,96) = 18.5, p < 0.05 (for interaction). Columns are mean values ± SD. The same uppercase letter within each POL treatment and the same lowercase letter within each concentration indicates no significant differences according to Student–Newman–Keuls test (p < 0.05). Full article ">

18 pages, 2351 KiB

Open AccessArticle

Broad-Spectrum Anti-Adhesive Coating Based on an Extracellular Polymer from a Marine Cyanobacterium

by Bruna Costa, Rita Mota, Paula Parreira, Paula Tamagnini, M. Cristina L. Martins and Fabíola Costa

Mar. Drugs 2019, 17(4), 243; https://doi.org/10.3390/md17040243 - 24 Apr 2019

Cited by 15 | Viewed by 4440

Abstract

Medical device-associated infections are a major health threat, representing about half of all hospital-acquired infections. Current strategies to prevent this problem based on device coatings with antimicrobial compounds (antibiotics or antiseptics) have proven to be insufficient, often toxic, and even promoting bacterial resistance. [...] Read more.

Medical device-associated infections are a major health threat, representing about half of all hospital-acquired infections. Current strategies to prevent this problem based on device coatings with antimicrobial compounds (antibiotics or antiseptics) have proven to be insufficient, often toxic, and even promoting bacterial resistance. Herein, we report the development of an infection-preventive coating (CyanoCoating) produced with an extracellular polymer released by the marine cyanobacterium Cyanothece sp. CCY 0110. CyanoCoating was prepared by spin-coating and its bacterial anti-adhesive efficiency was evaluated against relevant etiological agents (Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Escherichia coli) and platelets, both in the presence or absence of human plasma proteins. CyanoCoating cytotoxicity was assessed using the L929 fibroblasts cell line. CyanoCoating exhibited a smooth topography, low thickness and high hydrophilic properties with mild negative charge. The non-cytotoxic CyanoCoating prevented adhesion of all the bacteria tested (≤80%) and platelets (<87%), without inducing platelet activation (even in the presence of plasma proteins). The significant reduction in protein adsorption (<77%) confirmed its anti-adhesive properties. The development of this anti-adhesive coating is an important step towards the establishment of a new technological platform capable of preventing medical device-associated infections, without inducing thrombus formation in blood-contacting applications. Full article

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18 pages, 481 KiB

Open AccessReview

Biological Activities of Fucoidan and the Factors Mediating Its Therapeutic Effects: A Review of Recent Studies

by Yu Wang, Maochen Xing, Qi Cao, Aiguo Ji, Hao Liang and Shuliang Song

Mar. Drugs 2019, 17(3), 183; https://doi.org/10.3390/md17030183 - 20 Mar 2019

Cited by 325 | Viewed by 15145

Abstract

The marine acid polysaccharide fucoidan has attracted attention from both the food and pharmaceutical industries due to its promising therapeutic effects. Fucoidan is a polysaccharide that mainly consists of L-fucose and sulphate groups. Its excellent biological function is attributed to its unique biological [...] Read more.

The marine acid polysaccharide fucoidan has attracted attention from both the food and pharmaceutical industries due to its promising therapeutic effects. Fucoidan is a polysaccharide that mainly consists of L-fucose and sulphate groups. Its excellent biological function is attributed to its unique biological structure. Classical activities include antitumor, antioxidant, anticoagulant, antithrombotic, immunoregulatory, antiviral and anti-inflammatory effects. More recently, fucoidan has been shown to alleviate metabolic syndrome, protect the gastrointestinal tract, benefit angiogenesis and bone health. This review focuses on the progress in our understanding of the biological activities of fucoidan, highlighting its benefits for the treatment of human disease. We hope that this review can provide some theoretical basis and inspiration for the product development of fucoidan. Full article

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14 pages, 2095 KiB

Open AccessArticle

Metabolomic and Transcriptomic Analyses of Escherichia coli for Efficient Fermentation of L-Fucose

by Jungyeon Kim, Yu Eun Cheong, Inho Jung and Kyoung Heon Kim

Mar. Drugs 2019, 17(2), 82; https://doi.org/10.3390/md17020082 - 29 Jan 2019

Cited by 19 | Viewed by 5952

Abstract

L-Fucose, one of the major monomeric sugars in brown algae, possesses high potential for use in the large-scale production of bio-based products. Although fucose catabolic pathways have been enzymatically evaluated, the effects of fucose as a carbon source on intracellular metabolism in industrial [...] Read more.

L-Fucose, one of the major monomeric sugars in brown algae, possesses high potential for use in the large-scale production of bio-based products. Although fucose catabolic pathways have been enzymatically evaluated, the effects of fucose as a carbon source on intracellular metabolism in industrial microorganisms such as Escherichia coli are still not identified. To elucidate the effects of fucose on cellular metabolism and to find clues for efficient conversion of fucose into bio-based products, comparative metabolomic and transcriptomic analyses were performed on E. coli on L-fucose and on D-glucose as a control. When fucose was the carbon source for E. coli, integration of the two omics analyses revealed that excess gluconeogenesis and quorum sensing led to severe depletion of ATP, resulting in accumulation and export of fucose extracellularly. Therefore, metabolic engineering and optimization are needed for E. coil to more efficiently ferment fucose. This is the first multi-omics study investigating the effects of fucose on cellular metabolism in E. coli. These omics data and their biological interpretation could be used to assist metabolic engineering of E. coli producing bio-based products using fucose-containing brown macroalgae. Full article

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Graphical abstract
Full article ">Figure 1
Comparison of the growth and fermentation product profiles of E. coli cultured on fucose and glucose as the carbon source (mean ± SD): (A) cell density recorded as optical density at 600 nm (OD600); (B) concentrations of substrate; and (C) by-products (three independent replicates). Full article ">Figure 2
PCA (A) score and (B) loading plots of 102 intracellular metabolites of E. coli in the lag, exponential, and stationary phases cultured on fucose and glucose as the carbon source (six replicates; three independent replicates × two technical replicates). Full article ">Figure 3
MetaMapp analysis of 102 intracellular metabolites of E. coli cultured on fucose and glucose as the carbon source in: (A) the lag phase; (B) exponential phase; and (C) stationary phase. Classes of metabolites are represented by shapes. Significant increases and decreases in metabolite abundance are represented by color (p < 0.05). Magnitudes of fold changes are represented by the size of symbols and labels. Biochemical and structural similarities are represented by the orange and gray edges, respectively (six replicates; three independent replicates × two technical replicates). Full article ">Figure 4
Hierarchical clustering analysis (FDR adjusted p-value < 0.01, ANOVA) of significantly increased or decreased (A) intracellular and (B) extracellular metabolites of E. coli in the lag, exponential, and stationary phases cultured on fucose as the carbon source. Clustering of the model was based on Pearson’s correlation coefficient and average linkage methods (six replicates; three independent replicates × two technical replicates). Full article ">Figure 5
Comparison of transcription levels in (A) central carbon metabolism and (B) abundance of cofactors of E. coli in the exponential phase cultured on fucose and glucose. Significant changes to transcript levels are represented by color (p-value < 0.05, and fold changes > 2.0). Significant changes in cofactors are represented by * (three independent replicates; p-value < 0.05). Full article ">Figure 6
Heat map of 284 transcripts significantly changed (p-value < 0.05) in E. coli in the exponential phase cultured on fucose and glucose (three independent replicates). Full article ">

10 pages, 1727 KiB

Open AccessArticle

Activation of Human Dendritic Cells by Ascophyllan Purified from Ascophyllum nodosum

by Wei Zhang, Minseok Kwak, Hae-Bin Park, Takasi Okimura, Tatsuya Oda, Peter Chang-Whan Lee and Jun-O Jin

Mar. Drugs 2019, 17(1), 66; https://doi.org/10.3390/md17010066 - 19 Jan 2019

Cited by 14 | Viewed by 4374

Abstract

In our previous study, we showed that ascophyllan purified from Ascophyllum nodosum treatment promotes mouse dendritic cell (DC) activation in vivo, further induces an antigen-specific immune response and has anticancer effects in mice. However, the effect of ascophyllan has not been studied in [...] Read more.

In our previous study, we showed that ascophyllan purified from Ascophyllum nodosum treatment promotes mouse dendritic cell (DC) activation in vivo, further induces an antigen-specific immune response and has anticancer effects in mice. However, the effect of ascophyllan has not been studied in human immune cells, specifically in terms of activation of human monocyte-derived DCs (MDDCs) and human peripheral blood DCs (PBDCs). We found that the treatment with ascophyllan induced morphological changes in MDDCs and upregulated co-stimulatory molecules and major histocompatibility complex class I (MHC I) and MHC II expression. In addition, pro-inflammatory cytokine levels in culture medium was also dramatically increased following ascophyllan treatment of MDDCs. Moreover, ascophyllan promoted phosphorylation of ERK, p38 and JNK signaling pathways, and inhibition of p38 almost completely suppressed the ascophyllan-induced activation of MDDCs. Finally, treatment with ascophyllan induced activation of BDCA1 and BDCA3 PBDCs. Thus, these data suggest that ascophyllan could be used as an immune stimulator in humans. Full article

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Activation of human monocyte-derived dendritic cells (MDDCs) by ascophyllan. CD14+ monocytes were differentiated to MDDCs by culturing with 50 ng/mL of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 50 ng/mL of interleukin-4 (IL-4) for 6 days. (A) Changes in morphology are shown 24 h after treatment with PBS, ascophyllan (asco) or fucoidan (fuco). (B) Expression levels of CD80 (left panel) and CD83 (right panel) in MDDCs 24 h after treatment with different doses of ascophyllan. (C) Expression levels of co-stimulatory molecules were measured 24 h after treatment of PBS, ascophyllan (50 μg/mL) and fucoidan (50 μg/mL). Mean fluorescence intensity (MFI) levels of CD80, CD83, CD86, MHC class I and MHC class II in MDDCs are shown. Data are representative of or the average of analyses of 6 independent samples. ** p < 0.01. Full article ">Figure 2
Phosphorylation of mitogen-activated protein kinase (MAPK) signaling pathway in MDDCs by ascophyllan. (A) Phosphorylation of ERK, p38 and JNK was analyzed in MDDCs by western blotting after 1 h of ascophyllan (50 μg/mL) or fucoidan (50 μg/mL) treatment. (B and C) MDDCs were pre-treated with PD98059 (ERK inhibitor; 10 μM), SB203580 (p38 inhibitor; 2μM) or SP600125 (JNK inhibitor; 10 μM) for 1 h and then stimulated with ascophyllan for 24 h. (B) MFI levels of CD80 and (C) CD86 are shown. All data are representative of or the average of analyses of 6 independent samples. ** p < 0.01. Full article ">Figure 3
Production of pro-inflammatory cytokines from MDDCs by ascophyllan. MDDCs were treated with PBS, 50 μg/mL ascophyllan (asco) or 50 μg/mL fucoidan (fuco) for 24 h and culture medium was harvested. (A) The concentration of interleukin-6 (IL-6), IL-12 and TNF-α in a culture medium. (B) MDDCs were pre-treated with inhibitors as shown in <a href="#marinedrugs-17-00066-f002" class="html-fig">Figure 2</a>B,C, then cultured with PBS, ascophyllan or fucoidan for 24 h. IL-6, IL-12 and TNF-α levels were measured using ELISA. All data are the average of analyses of 6 independent samples. ** p < 0.01. Full article ">Figure 4
Activation of peripheral blood dendritic cell (PBDC) subsets following treatment with ascophyllan. Peripheral blood mononuclear cells (PBMCs) were cultured with PBS, 50 μg/mL ascophyllan (asco) or 50 μg/mL fucoidan (fuco) for 24 h. (A) BDCA1+ and BDCA3+ PBDCs were defined by flow cytometry from CD11c+lineage− live leukocytes of PBMCs. (B) Co-stimulatory molecules and MHC class I and II expression in BDCA1+ and BDCA3+ PBDCs are shown. (C) PD98059 (ERK inhibitor; 10 μM), SB203580 (p38 inhibitor; 2 μM) or SP600125 (JNK inhibitor; 10 μM) were pre-treated in PBDCs for 1 h and the PBDCs were stimulated with 50 μg/mL ascophyllan for 24 h. Expression levels of CD83 were measured in BDCA1+ and BDCA3+ PBDCs. (D) Concentration of IL-6, IL-12 and TNF-α in a culture medium of PBMCs. (E) Concentrations of IL-6, IL-12, TNF-α in culture medium from <a href="#marinedrugs-17-00066-f004" class="html-fig">Figure 4</a>C were measured using ELISA. All data are representative of or the average of analyses of 6 independent samples. ** p < 0.01. Full article ">

14 pages, 3073 KiB

Open AccessArticle

Protective Effect of Low Molecular Weight Seleno-Aminopolysaccharide on the Intestinal Mucosal Oxidative Damage

by Zheng-Shun Wen, Zhen Tang, Li Ma, Tian-Long Zhu, You-Ming Wang, Xing-Wei Xiang and Bin Zheng

Mar. Drugs 2019, 17(1), 64; https://doi.org/10.3390/md17010064 - 18 Jan 2019

Cited by 15 | Viewed by 3855

Abstract

Low molecular weight seleno-aminopolysaccharide (LSA) is an organic selenium compound comprising selenium and low molecular weight aminopolysaccharide (LA), a low molecular weight natural linear polysaccharide derived from chitosan. LSA has been found to exert strong pharmacological activity. In this study, we aimed to [...] Read more.

Low molecular weight seleno-aminopolysaccharide (LSA) is an organic selenium compound comprising selenium and low molecular weight aminopolysaccharide (LA), a low molecular weight natural linear polysaccharide derived from chitosan. LSA has been found to exert strong pharmacological activity. In this study, we aimed to investigate the protective effect of LSA on intestinal mucosal oxidative stress in a weaning piglet model by detecting the growth performance, intestinal mucosal structure, antioxidant indices, and expression level of intracellular transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its related factors. Our results indicated that LSA significantly increased the average daily gain and feed/gain (p < 0.05), suggesting that LSA can effectively promote the growth of weaning piglets. The results of scanning electron microscope (SEM) microscopy showed that LSA effectively reduced intestinal damage, indicating that LSA improved the intestinal stress response and protected the intestinal structure integrity. In addition, diamine oxidase (DAO) and d-lactic acid (d-LA) levels remarkably decreased in LSA group compared with control group (p < 0.05), suggesting that LSA alleviated the damage and permeability of weaning piglets. LSA significantly increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) levels, but decreased malondialdehyde (MDA) level, indicating that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress in weaning piglets. RT-PCR results showed that LSA significantly increased GSH-Px1, GSH-Px2, SOD-1, SOD-2, CAT, Nrf2, HO-1, and NQO1 gene expression (p < 0.05). Western blot analysis revealed that LSA activated the Nrf2 signaling pathway by downregulating the expression of Keap1 and upregulating the expression of Nrf2 to protect intestinal mucosa against oxidative stress. Collectively, LSA reduced intestinal mucosal damage induced by oxidative stress via Nrf2-Keap1 pathway in weaning stress of infants. Full article

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Effects of LSA on diarrhea rate. Bars labeled with different letters (a–d) were significantly different (p < 0.05) from each other. Full article ">Figure 2
Effects of LSA on intestinal morphology (SEM, 200×). Full article ">Figure 3
Effects of LSA on the level of diamine oxidase (DAO) and d-lactic acid (d-LA) in serum. Bars labeled with different letters (a–d) were significantly different (p < 0.05) from each other. Full article ">Figure 4
Effects of LSA on the antioxidant indices in serum. Bars labeled with different letters (a–d) were significantly different (p < 0.05) from each other. Full article ">Figure 5
Effect of LSA on the gene expression levels of tight junction proteins in ileum. Bars labeled with different letters (a, b) were significantly different (p < 0.05) from each other. Full article ">Figure 6
Effects of LSA on the expression of antioxidant genes in ileum. The mRNA expression level of antioxidant genes (GSH-Px1 (a), GSH-Px2 (b), SOD1 (c), SOD2 (d), CAT (e), Nrf2 (f), NQO1 (g), HO-1 (h). Bars labeled with different letters (a–d) were significantly different (p < 0.05) from each other. Full article ">Figure 7
Effects of LSA on the Keap1–Nrf2 signaling pathway in ileum. Bars labeled with different letters (a-d) were significantly different (p < 0.05) from each other. Full article ">

15 pages, 2811 KiB

Open AccessCommunication

Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen

by Monika Corban, Mark Ambrose, Joanne Pagnon, Damien Stringer, Sam Karpiniec, Ahyoung Park, Raj Eri, J Helen Fitton and Nuri Gueven

Mar. Drugs 2019, 17(1), 54; https://doi.org/10.3390/md17010054 - 14 Jan 2019

Cited by 10 | Viewed by 4946

Abstract

Fucoidan, the sulfated fucose-rich polysaccharide derived from brown macroalgae, was reported to display some anti-cancer effects in in vitro and in vivo models that included apoptosis and cell cycle arrest. The proposed mechanisms of action involve enhanced immune surveillance and direct pro-apoptotic effects [...] Read more.

Fucoidan, the sulfated fucose-rich polysaccharide derived from brown macroalgae, was reported to display some anti-cancer effects in in vitro and in vivo models that included apoptosis and cell cycle arrest. The proposed mechanisms of action involve enhanced immune surveillance and direct pro-apoptotic effects via the activation of cell signaling pathways that remain largely uncharacterized. This study aimed to identify cellular pathways influenced by fucoidan using an unbiased genetic approach to generate additional insights into the anti-cancer effects of fucoidan. Drug–gene interactions of Undaria pinnatifida fucoidan were assessed by a systematic screen of the entire set of 4,733 halpoid Saccharomyces cerevsiae gene deletion strains. Some of the findings were confirmed using cell cycle analysis and DNA damage detection in non-immortalized human dermal fibroblasts and colon cancer cells. The yeast deletion library screen and subsequent pathway and interactome analysis identified global effects of fucoidan on a wide range of eukaryotic cellular processes, including RNA metabolism, protein synthesis, sorting, targeting and transport, carbohydrate metabolism, mitochondrial maintenance, cell cycle regulation, and DNA damage repair-related pathways. Fucoidan also reduced clonogenic survival, induced DNA damage and G1-arrest in colon cancer cells, while these effects were not observed in non-immortalized human fibroblasts. Our results demonstrate global effects of fucoidan in diverse cellular processes in eukaryotic cells and further our understanding about the inhibitory effect of Undaria pinnatifida fucoidan on the growth of human cancer cells. Full article

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Figure 1
(A) Pathway analysis of identified genes that resulted in reduced growth of S. cerevisiae in the presence of UPF. Pathway analysis was performed with String software (Version 10.5) using an interaction score of 0.9 (‘highest confidence’). The figure only shows connected genes with disconnected nodes hidden. (B) Pathway analysis of identified genes that resulted in increased growth of S. cerevisiae in the presence of UPF. Pathway analysis was performed with String software (Version 10.5) using an interaction score of 0.9 (‘highest confidence’). The figure only shows connected genes with disconnected nodes hidden. (C) Pathway analysis of all identified genes that interacted with UPF. Pathway analysis was performed with String software (Version 10.5) using an interaction score of 0.9 (‘highest confidence’). The figure only shows connected genes with disconnected nodes hidden. Full article ">Figure 1 Cont.
(A) Pathway analysis of identified genes that resulted in reduced growth of S. cerevisiae in the presence of UPF. Pathway analysis was performed with String software (Version 10.5) using an interaction score of 0.9 (‘highest confidence’). The figure only shows connected genes with disconnected nodes hidden. (B) Pathway analysis of identified genes that resulted in increased growth of S. cerevisiae in the presence of UPF. Pathway analysis was performed with String software (Version 10.5) using an interaction score of 0.9 (‘highest confidence’). The figure only shows connected genes with disconnected nodes hidden. (C) Pathway analysis of all identified genes that interacted with UPF. Pathway analysis was performed with String software (Version 10.5) using an interaction score of 0.9 (‘highest confidence’). The figure only shows connected genes with disconnected nodes hidden. Full article ">Figure 2
Effect of UPF on metabolic activity/viability. Human colon carcinoma cells (HCT-116) were exposed to UPF concentrations of up to 100 µg/mL for 24 h before viability was assessed using WST-1 reagent. Data represent one typical experiment out of up to four independent experiments. WST-1 absorption data were standardized on protein content for each well, represent the mean of six individual wells per experiment and are expressed as % viability compared to the untreated control cells. Error bars represent SD with *: p < 0.05. Hydrogen peroxide (H, 100 µM) was used as a positive control for toxicity. Full article ">Figure 3
Effect of UPF on colony formation. Human colon carcinoma cells (HCT-116, A) and human non-immortalized dermal fibroblasts (HDF, B) were exposed to UPF concentrations up to 100 µg/mL in a colony formation assay. Data represent one typical experiment out of up to four independent experiments. Data is expressed as the mean +/− SD of four plates and expressed as % colony formation compared to the untreated control cells. Error bars represent SD with #: p < 0.05 and * p < 0.001. Full article ">Figure 4
DNA damage induction by UPF. Human colon carcinoma cells (HCT-116, A, C) and human non-immortalized dermal fibroblasts (HDF, A,B) were exposed to 100 µg/mL UPF before γH2AX immunostaining was performed (A) Data represents the mean of 3 experiments and expressed as % γH2AX-positive cells. Error bars represent SD with *: p < 0.001. (B) Data represent one typical experiment out of three experiments for HDF. n/a: cells excluded from analysis due to unquantifiable staining pattern. (C) Representative images for UPF-induced induction of nuclear γH2AX foci in HCT-116 cells. H2O2-treatment (100 µM, 30 min) was used as a positive control. Merged images represent software generated false color overlays of DAPI and γH2AX signals. Full article ">Figure 4 Cont.
DNA damage induction by UPF. Human colon carcinoma cells (HCT-116, A, C) and human non-immortalized dermal fibroblasts (HDF, A,B) were exposed to 100 µg/mL UPF before γH2AX immunostaining was performed (A) Data represents the mean of 3 experiments and expressed as % γH2AX-positive cells. Error bars represent SD with *: p < 0.001. (B) Data represent one typical experiment out of three experiments for HDF. n/a: cells excluded from analysis due to unquantifiable staining pattern. (C) Representative images for UPF-induced induction of nuclear γH2AX foci in HCT-116 cells. H2O2-treatment (100 µM, 30 min) was used as a positive control. Merged images represent software generated false color overlays of DAPI and γH2AX signals. Full article ">Figure 5
Effect of UPF on cell cycle distribution. HCT 116 cells were treated with 100 µg/mL UPF for up to 72 h and cell cycle distribution was assessed by flow cytometry. Data represents the mean of four independent experiments performed over a two-month time period. Error bars represent SD with *: p < 0.01. Full article ">

18 pages, 3327 KiB

Open AccessArticle

Structure Analysis and Anti-Tumor and Anti-Angiogenic Activities of Sulfated Galactofucan Extracted from Sargassum thunbergii

by Weihua Jin, Wanli Wu, Hong Tang, Bin Wei, Hong Wang, Jiadong Sun, Wenjing Zhang and Weihong Zhong

Mar. Drugs 2019, 17(1), 52; https://doi.org/10.3390/md17010052 - 11 Jan 2019

Cited by 34 | Viewed by 4543

Abstract

Sulfated galactofucan (ST-2) was obtained from Sargassum thunbergii. It was then desulfated to obtain ST-2-DS, and autohydrolyzed and precipitated by ethanol to obtain the supernatant (ST-2-S) and precipitate (ST-2-C). ST-2-C was further fractionated by gel chromatography into two fractions, ST-2-H (high molecular [...] Read more.

Sulfated galactofucan (ST-2) was obtained from Sargassum thunbergii. It was then desulfated to obtain ST-2-DS, and autohydrolyzed and precipitated by ethanol to obtain the supernatant (ST-2-S) and precipitate (ST-2-C). ST-2-C was further fractionated by gel chromatography into two fractions, ST-2-H (high molecular weight) and ST-2-L (low molecular weight). Mass spectrometry (MS) of ST-2-DS was performed to elucidate the backbone of ST-2. It was shown that ST-2-DS contained a backbone of alternating galactopyranose residues (Gal)_n (n ≤ 3) and fucopyranose residues (Fuc)_n. In addition, ST-2-S was also determined by MS to elucidate the branches of ST-2. It was suggested that sulfated fuco-oligomers might be the branches of ST-2. Compared to the NMR spectra of ST-2-H, the spectra of ST-2-L was more recognizable. It was shown that ST-2-L contain a backbone of (Gal)_n and (Fuc)_n, sulfated mainly at C4 of Fuc, and interspersed with galactose (the linkages were likely to be 1→2 and 1→6). Therefore, ST-2 might contain a backbone of (Gal)_n (n ≤ 3) and (Fuc)_n. The sulfation pattern was mainly at C4 of fucopyranose and partially at C4 of galactopyranose, and the branches were mainly sulfated fuco-oligomers. Finally, the anti-tumor and anti-angiogenic activities of ST-2 and its derivates were determined. It was shown that the low molecular-weight sulfated galactofucan, with higher fucose content, had better anti-angiogenic and anti-tumor activities. Full article

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2018

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13 pages, 3621 KiB

Open AccessArticle

Isolation, Characterization, and Pharmaceutical Applications of an Exopolysaccharide from Aerococcus Uriaeequi

by Chunlei Wang, Qiuping Fan, Xiaofei Zhang, Xiaoping Lu, Yanrui Xu, Wenxing Zhu, Jie Zhang, Wen Hao and Lujiang Hao

Mar. Drugs 2018, 16(9), 337; https://doi.org/10.3390/md16090337 - 16 Sep 2018

Cited by 34 | Viewed by 4977

Abstract

Many marine bacteria secrete exopolysaccharides (EPSs), which are made up of a substantial component of the macro-molecules surrounding cells. Recently, the wide demand for EPSs for food, cosmetics, pharmaceutical and other applications has led to great interest in them. In this study, an [...] Read more.

Many marine bacteria secrete exopolysaccharides (EPSs), which are made up of a substantial component of the macro-molecules surrounding cells. Recently, the wide demand for EPSs for food, cosmetics, pharmaceutical and other applications has led to great interest in them. In this study, an EPS produced by marine bacteria Aerococcus uriaeequi HZ strains (EPS-A) was isolated and purified to examine its structure and biological function. The molecular weight of EPS-A analyzed by high-performance liquid gel filtration chromatography (HPGFC) is found to have a number average of 2.22 × 10⁵ and weight average of 2.84 × 10⁵, respectively. High-performance liquid chromatography (HPLC) and Fourier-transform–infrared (FT–IR) analysis indicate that EPS-A was a polysaccharide composed of glucose and a little mannose. In addition, the flocculating rate of sewage of EPS-A was 79.90%. The hygroscopicity studies showed that hygroscopicity of EPS-A was higher than chitosan but lower than that of sodium hyaluronate. The moisture retention of EPS-A showed similar retention activity to both chitosan and sodium hyaluronate. EPS-A also can scavenge free radicals including both OH• free radical and O₂•⁻ free radical and the activity to O₂•⁻ free radical is similar to vitamin C. Safety assessment on mice indicated that the EPS-A is safe for external use and oral administration. EPS-A has great potential for applications in medicine due to its characteristics mentioned above. Full article

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12 pages, 3585 KiB

Open AccessArticle

Characterization of a Novel PolyM-Preferred Alginate Lyase from Marine Vibrio splendidus OU02

by Jingjing Zhuang, Keke Zhang, Xiaohua Liu, Weizhi Liu, Qianqian Lyu and Aiguo Ji

Mar. Drugs 2018, 16(9), 295; https://doi.org/10.3390/md16090295 - 22 Aug 2018

Cited by 35 | Viewed by 4667

Abstract

Alginate lyases are enzymes that degrade alginate into oligosaccharides which possess a variety of biological activities. Discovering and characterizing novel alginate lyases has great significance for industrial and medical applications. In this study, we reported a novel alginate lyase, AlyA-OU02, derived from the [...] Read more.

Alginate lyases are enzymes that degrade alginate into oligosaccharides which possess a variety of biological activities. Discovering and characterizing novel alginate lyases has great significance for industrial and medical applications. In this study, we reported a novel alginate lyase, AlyA-OU02, derived from the marine Vibrio splendidus OU02. The BLASTP searches showed that AlyA-OU02 belonged to polysaccharide lyase family 7 (PL7) and contained two consecutive PL7 domains, which was rare among the alginate lyases in PL7 family. Both the two domains, AlyA^a and AlyA^b, had lyase activities, while AlyA^a exhibited polyM preference, and AlyA^b was polyG-preferred. In addition, the enzyme activity of AlyA^a was much higher than AlyA^b at 25 °C. The full-length enzyme of AlyA-OU02 showed polyM preference, which was the same as AlyA^a. AlyA^a degraded alginate into di-, tri-, and tetra-alginate oligosaccharides, while AlyA^b degraded alginate into tri-, tetra-, and penta-alginate oligosaccharides. The degraded products of AlyA-OU02 were similar to AlyA^a. Our work provided a potential candidate in the application of alginate oligosaccharide production and the characterization of the two domains might provide insights into the use of alginate of this organism. Full article

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Sequence properties of the alginate lyase AlyA-OU02 from marine Vibrio splendidus OU02. (A) Module organization of AlyA-OU02. The two alginate_lyase 2 modules were putative catalytic domains (Ser40 to Ala264, Trp278 to His563). The full-length protein and the two alginate_lyase 2 modules were expressed to yield the recombinant protein AlyA-OU02 (Ser1 to Tyr564), AlyAa (Ser1 to Ser275), and AlyAb (Asn276 to Tyr564). The indicated amino acid residues were hypothesized catalytic sites. (B) Comparison of the partial amino acid sequences of AlyAa and AlyAb with PL7 alginate lyases AlyVI from Vibrio sp. QY101 (AAP45155.1), Algb from Vibrio sp. W13 (AIY22661.1), NitAly from Nitratiruptor sp. SB155-2 (BAF69299.1), AlxM from Photobacterium sp. ATCC 43367 (CAA49630.1). Full article ">Figure 2
SDS-PAGE analysis of purified AlyA-OU02, AlyAa, and AlyAb. Lane M, molecular weight markers; Lane 1, purified AlyA-OU02; Lane 2, purified AlyAa; Lane 3, purified AlyAb. Full article ">Figure 3
Enzyme activity assay of AlyA-OU02, AlyAa and AlyAb toward alginate. The measurement was carried out in Tris-HCl buffer with 200 mM NaCl (pH 7.5) using 0.2% alginate as substrate. Full article ">Figure 4
Effects of temperature and pH on enzyme activities of AlyA-OU02, AlyAa, and AlyAb. (A) Optimal temperatures of the enzymes were determined in Tris-HCl buffer with 200 mM NaCl (pH 7.5) at different temperatures. (B) Optimal pH of the enzymes was determined at 25 °C in NaAc-HAc buffer (pH 5–6) and Tris-HCl buffer (pH 7–10). Full article ">Figure 5
Thermostabilities of AlyA-OU02, AlyAa, and AlyAb. Full article ">Figure 6
Effects of NaCl and metal ions on enzymatic activities of AlyA-OU02, AlyAa, and AlyAb. (A) Influence of the concentration of NaCl. (B) Influence of the metal ions on AlyA-OU02. (C) Influence of the metal ions on AlyAa. (D) Influence of the metal ions on AlyAb. The enzymatic activity without metal ions served as the control, and the enzymatic activity was designated as 100%. Full article ">Figure 7
Substrate specificities of AlyA-OU02, AlyAa, and AlyAb. (A) Relative enzyme activities of AlyAa toward alginate, polyM, and polyG. (B) Relative enzyme activities of AlyAb toward alginate, polyM, and polyG. (C) Relative enzyme activities of AlyA-OU02 toward alginate, polyM, and polyG. Full article ">Figure 8
TLC analysis of the hydrolytic products of AlyA-OU02, AlyAa, and AlyAb. Solutions of 0.2% (w/v) alginate, polyG, and polyM were each incubated with 5 uM AlyA-OU02, AlyAa, and AlyAb, respectively, at 25 °C for 1 h. Lane 1: alginate; lane 2–4: hydrolytic products of AlyA-OU02, AlyAa, and AlyAb toward alginate; lane 5: polyG; lane 6–8: hydrolytic products of AlyA-OU02, AlyAa, and AlyAb toward polyG; lane 9: polyM; lane 10–12: hydrolytic products of AlyA-OU02, AlyAa, and AlyAb toward polyM; lane 13: DP2, DP3, DP4, and DP5 mean the alginate disaccharide, trisaccharide, tetrasaccharide, and pentasaccharide, respectively; lane 14: hydrolytic products of AlyAa toward polyM. Full article ">

15 pages, 1330 KiB

Open AccessArticle

Extraction and Yield Optimisation of Fucose, Glucans and Associated Antioxidant Activities from Laminaria digitata by Applying Response Surface Methodology to High Intensity Ultrasound-Assisted Extraction

by Marco Garcia-Vaquero, Gaurav Rajauria, Brijesh Tiwari, Torres Sweeney and John O’Doherty

Mar. Drugs 2018, 16(8), 257; https://doi.org/10.3390/md16080257 - 30 Jul 2018

Cited by 72 | Viewed by 8306

Abstract

The objectives of this study were to employ response surface methodology (RSM) to investigate and optimize the effect of ultrasound-assisted extraction (UAE) variables, temperature, time and amplitude on the yields of polysaccharides (fucose and total glucans) and antioxidant activities (ferric reducing antioxidant power [...] Read more.

The objectives of this study were to employ response surface methodology (RSM) to investigate and optimize the effect of ultrasound-assisted extraction (UAE) variables, temperature, time and amplitude on the yields of polysaccharides (fucose and total glucans) and antioxidant activities (ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryl-hydrazyl radical scavenging activity (DPPH)) from Laminaria digitata, and to explore the suitability of applying the optimum UAE conditions for L. digitata to other brown macroalgae (L. hyperborea and Ascophyllum nodosum). The RSM with three-factor, four-level Box-Behnken Design (BBD) was used to study and optimize the extraction variables. A second order polynomial model fitted well to the experimental data with R² values of 0.79, 0.66, 0.64, 0.73 for fucose, total glucans, FRAP and DPPH, respectively. The UAE parameters studied had a significant influence on the levels of fucose, FRAP and DPPH. The optimised UAE conditions (temperature = 76 °C, time = 10 min and amplitude = 100%) achieved yields of fucose (1060.7 ± 70.6 mg/100 g dried seaweed (ds)), total glucans (968.6 ± 13.3 mg/100 g ds), FRAP (8.7 ± 0.5 µM trolox/mg freeze-dried extract (fde)) and DPPH (11.0 ± 0.2%) in L. digitata. Polysaccharide rich extracts were also attained from L. hyperborea and A. nodosum with variable results when utilizing the optimum UAE conditions for L. digitata. Full article

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14 pages, 3233 KiB

Open AccessArticle

Glycosaminoglycans from a Sea Snake (Lapemis curtus): Extraction, Structural Characterization and Antioxidant Activity

by Mingyue Bai, Wenwei Han, Xia Zhao, Qingchi Wang, Yanyun Gao and Shiming Deng

Mar. Drugs 2018, 16(5), 170; https://doi.org/10.3390/md16050170 - 18 May 2018

Cited by 18 | Viewed by 4797

Abstract

Sea snakes have wide application prospects in medicine, health food and other fields. Several novel polysaccharides were successfully obtained from the skin and the meat of a sea snake (Lapemis curtus). The structures of polysaccharides LSP3 and LMP3, which were extracted [...] Read more.

Sea snakes have wide application prospects in medicine, health food and other fields. Several novel polysaccharides were successfully obtained from the skin and the meat of a sea snake (Lapemis curtus). The structures of polysaccharides LSP3 and LMP3, which were extracted and purified from Lapemis curtus, were determined to be new and highly heterogenic glycosaminoglycans (GAGs) by means of FT-IR, ESI-MS/MS and NMR. LSP3 is a hybrid dermatan sulfate (DS) and composed of 48% 4-sulfated disaccharides (Di4S), 42% 6-sulfated disaccharides (Di6S) and 5% disulfated disaccharides (Di2,6S), while LMP3 is a hybrid chondroitin sulfate (CS) and composed of 70% Di4S, 20% Di6S, and 8% Di2,6S. More importantly, LSP3 and LMP3 showed a strong scavenging ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, iron (Fe²⁺) chelating activity and total antioxidant capacity in vitro, especially LSP3, with high contents of uronic acid and sulfate, which possessed a higher scavenging ability of DPPH radicals than other fractions. These data suggested that the sea snake polysaccharides could be promising candidates for natural antioxidant ingredients. Full article

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15 pages, 1969 KiB

Open AccessArticle

Dietary Polysaccharide from Enteromorpha Clathrata Modulates Gut Microbiota and Promotes the Growth of Akkermansia muciniphila, Bifidobacterium spp. and Lactobacillus spp.

by Qingsen Shang, Ya Wang, Lin Pan, Qingfeng Niu, Chao Li, Hao Jiang, Chao Cai, Jiejie Hao, Guoyun Li and Guangli Yu

Mar. Drugs 2018, 16(5), 167; https://doi.org/10.3390/md16050167 - 17 May 2018

Cited by 56 | Viewed by 7293

Abstract

Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut [...] Read more.

Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of Bifidobacterium spp. and Akkermansia muciniphila, a next-generation probiotic bacterium, whereas in males, ECP increased the population of Lactobacillus spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management. Full article

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Administration of ECP significantly changed the structure of the gut microbiota. PCA score plot of the first and second components for the gut microbiome in male (A) and female mice (B). Blue indicates control groups, red indicates low dose groups and green indicates high dose groups. The PCA score plot was constructed based on the OTUs of the microbiota in male mice and female mice. Full article ">Figure 2
Dietary ECP increased the richness and diversity of the gut microbiota. Chao1 (A) and observed species (B) were used as the richness estimators. Shannon indices (C) was used as the diversity estimator. a: p < 0.05 vs. MN group; b: p < 0.05 vs. FN group. Full article ">Figure 3
Response of the gut microbiota to ECP treatment at the phylum (A) and genus (B) levels. The relative abundances of the gut bacteria presented here were calculated by averaging the data obtained from the six replicates within each group. Full article ">Figure 4
The taxonomic cladogram obtained from LEfSe analysis of gut microbiota in different groups. The microbial compositions of the male and female mice were compared at different evolutionary levels. A significant value of less than 0.05 was used as a threshold for the LEfSe analysis. Full article ">Figure 5
The LDA score obtained from LEfSe analysis of gut microbiota in different groups. A LDA effect size of more than 2 was used as a threshold for the LEfSe analysis. Full article ">Figure 6
Intake of ECP significantly increased the abundances of Bifidobacterium spp. (A), Lactobacillus spp. (B) and A. muciniphila (C) in C57BL/6J mice. The solid line represents the average abundances of Bifidobacterium spp. (A), Lactobacillus spp. (B) and A. muciniphila (C) of the six replicates within each group; the dash line represents the median abundances of Bifidobacterium spp. (A), Lactobacillus spp. (B) and A. muciniphila (C) of the six replicates within each group. The differences in the abundances of the probiotic bacteria between treated mice and control mice were evidenced to be significant at p < 0.05 by LEfSe analysis. Full article ">Figure 7
ECP treatment reduced body weight (A,B), energy intake (C,D) and serum LBP levels (E) in C57BL/6J mice. * p < 0.05 vs. the control group. Full article ">

2017

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2153 KiB

Open AccessArticle

The Anti-Inflammatory Effect and Structure of EPCP1-2 from Crypthecodinium cohnii via Modulation of TLR4-NF-κB Pathways in LPS-Induced RAW 264.7 Cells

by Xiaolei Ma, Baolong Xie, Jin Du, Aijun Zhang, Jianan Hao, Shuxun Wang, Jing Wang and Junrui Cao

Mar. Drugs 2017, 15(12), 376; https://doi.org/10.3390/md15120376 - 1 Dec 2017

Cited by 14 | Viewed by 5156

Abstract

Exopolysaccharide from Crypthecodinium cohnii (EPCP1-2) is a marine exopolysaccharide that evidences a variety of biological activities. We isolated a neutral polysaccharide from the fermentation liquid of Crypthecodinium cohnii (CP). In this study, a polysaccharide that is derived from Crypthecodinium cohnii were analyzed and [...] Read more.

Exopolysaccharide from Crypthecodinium cohnii (EPCP1-2) is a marine exopolysaccharide that evidences a variety of biological activities. We isolated a neutral polysaccharide from the fermentation liquid of Crypthecodinium cohnii (CP). In this study, a polysaccharide that is derived from Crypthecodinium cohnii were analyzed and its anti-inflammatory effect was evaluated on protein expression of toll-like receptor 4 and nuclear factor κB pathways in macrophages. The structural characteristics of EPCP1-2 were characterized by GC (gas chromatography) and GC-MS (gas Chromatography-Mass Spectrometer) analyses. The molecular weight was about 82.5 kDa. The main chain of EPCP1-2 consisted of (1→6)-linked mannopyranosyl, (1→6)-linked glucopyranosyl, branched-chain consisted of (1→3,6)-linked galactopyranosyl and terminal consisted of t-l-Rhapyranosyl. The in vitro anti-inflammatory activity was representated through assay of proliferation rate, pro-inflammatory factor (NO) and expressions of proteins on RAW 264.7, the macrophage cell line. The results revealed that EPCP1-2 exhibited significant anti-inflammatory activity by regulating the expression of toll-like receptor 4, mitogen-activated protein kinases, and Nuclear Factor-κB protein. Full article

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5977 KiB

Open AccessArticle

Degradation of Polysaccharides from Grateloupia filicina and Their Antiviral Activity to Avian Leucosis Virus Subgroup J

by Yuhao Sun, Xiaolin Chen, Ziqiang Cheng, Song Liu, Huahua Yu, Xueqin Wang and Pengcheng Li

Mar. Drugs 2017, 15(11), 345; https://doi.org/10.3390/md15110345 - 3 Nov 2017

Cited by 22 | Viewed by 4493

Abstract

In this study, polysaccharides from Grateloupia filicinia (GFP) were extracted and several low molecular weight (Mw) G. filicina polysaccharides (LGFPs) were prepared by the hydrogen peroxide (H₂O₂) oxidation method. Additionally, the effect of different experimental conditions on the degradation [...] Read more.

In this study, polysaccharides from Grateloupia filicinia (GFP) were extracted and several low molecular weight (Mw) G. filicina polysaccharides (LGFPs) were prepared by the hydrogen peroxide (H₂O₂) oxidation method. Additionally, the effect of different experimental conditions on the degradation of GFP was determined. Results showed that the GFP degradation rate was positively related to H₂O₂ concentration and temperature, and negatively related to pH. Chemical analysis and Fourier transform infrared spectra (FT-IR) of GFP and LGFPs showed that the degradation caused a slight decrease of total sugar and sulfate content. However, there was no obvious change for monosaccharide contents. Then, the anti-ALV-J activity of GFP and LGFPs were determined in vitro. Results revealed that all of the samples could significantly inhibit ALV-J and lower Mw LGFPs exhibited a stronger suppression, and that the fraction LGFP-3 with Mw 8.7 kDa had the best effect. In addition, the reaction phase assays showed that the inhibition effect was mainly because of the blocking virus adsorption to host cells. Moreover, real-time PCR, western-blot, and IFA were further applied to evaluate the blocking effects of LGFP-3. Results showed that the gene relative expression and gp85 protein for LGFPS-3 groups were all reduced. Data from IFA showed that there was less virus infected cells for 1000 and 200 μg/mL LGFPS-3 groups when compared to virus control. Therefore, lower Mw polysaccharides from G. filicina might supply a good choice for ALV-J prevention and treatment. Full article

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1755 KiB

Open AccessArticle

The Identification of a SIRT6 Activator from Brown Algae Fucus distichus

by Minna K. Rahnasto-Rilla, Padraig McLoughlin, Tomasz Kulikowicz, Maire Doyle, Vilhelm A. Bohr, Maija Lahtela-Kakkonen, Luigi Ferrucci, Maria Hayes and Ruin Moaddel

Mar. Drugs 2017, 15(6), 190; https://doi.org/10.3390/md15060190 - 21 Jun 2017

Cited by 37 | Viewed by 8183

Abstract

Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from [...] Read more.

Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from five brown algae (Fucus dichitus, Fucus vesiculosus (Linnaeus), Cytoseira tamariscofolia, Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation. Three of the five macroalgal extracts caused a significant increase of H3K9 deacetylation, and the effect was most pronounced for F. dichitus. The compound responsible for this in vitro activity was identified by mass spectrometry as fucoidan. Full article

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Graphical abstract

Graphical abstract
Full article ">Figure 1
SIRT6 deacetylation activity in the presence of five species of brown algae extracts. The change of SIRT6 deacetylation in the presence of 0.5 mg/mL (grey) and 1.0 mg/mL (light grey) extracts is compared to controls with 500 µM NAD+ and 40 µM H3K9Ac with 30 min of incubation time. The data are presented as means ± SD, n = 3. Full article ">Figure 2
HPLC chromatogram of F. distichus and its separation into eight fractions using Zorbax Eclipse XDB-C18 column (4.6 mm × 50 mm, 1.8 µm). The collected fractions: F1 = 0.4–0.5 min; F7 = 5.4–5.5 min. Full article ">Figure 3
SIRT6 deacetylation activity (fold activity relative to control) of fractions (F1–F8) from F. distichus in the presence of 0.5 mg/mL (grey) and 1.0 mg/mL (light grey) fractions (F1–F8) with 500 µM NAD+ and 40 µM H3K9Ac with 30 min of incubation time. The data are presented as means ± SD, n = 3. Full article ">Figure 4
HPLC–MS analysis of subfraction F1 in negative ionization mode with a scan range of m/z 150–600. Full article ">Figure 5
Reported structural elements for fucoidan isolated from the brown seaweeds (A) F. distichus, (B) F. vesiculosus. Modified from [<a href="#B24-marinedrugs-15-00190" class="html-bibr">24</a>,<a href="#B25-marinedrugs-15-00190" class="html-bibr">25</a>]. Full article ">Figure 6
(A) Dose-response curve of the extract sub-fraction of F1 (●) in the presence of 500 µM NAD+ and 40 µM H3K9Ac with 30 min of incubation time. The data are presented as means ± SD, n = 3; (B) Dose-response curve of fucoidan (■) on SIRT6 deacetylation activity in the presence of 500 µM NAD+ and 40 µM H3K9Ac with 30 min of incubation time. The data are presented as means ± SD, n = 3. Full article ">Figure 7
Western blot method for the in vitro SIRT6 deacetylation assay. Serially diluted concentrations of a SIRT6 stimulator (1–16 µg/mL) were incubated for 30 min at 37 °C in the presence of 1 μg/well of a purified recombinant GST-SIRT6 protein, 2 μg purified whole chicken core histones with 500 μM NAD+ in 25 mM Tris-HCl, pH 8.0. (A) Acetylation level was detected with anti-H3K9Ac antibody and normalized to total H3 histone. Values indicate final fucoidan concentration in µg/mL. Molecular weight markers in kDa. (B) Quantification of H3K9 deacetylation. Values represent the averages of three experiments; error bars indicate standard deviation. Full article ">

2924 KiB

Open AccessArticle

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles

by Zongrui Tong, Yu Chen, Yang Liu, Li Tong, Jiamian Chu, Kecen Xiao, Zhiyu Zhou, Wenbo Dong and Xingwu Chu

Mar. Drugs 2017, 15(4), 91; https://doi.org/10.3390/md15040091 - 11 Apr 2017

Cited by 71 | Viewed by 6524

Abstract

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) [...] Read more.

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca²⁺ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. Full article

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2601 KiB

Open AccessArticle

Degradation of Marine Algae-Derived Carbohydrates by Bacteroidetes Isolated from Human Gut Microbiota

by Miaomiao Li, Qingsen Shang, Guangsheng Li, Xin Wang and Guangli Yu

Mar. Drugs 2017, 15(4), 92; https://doi.org/10.3390/md15040092 - 24 Mar 2017

Cited by 70 | Viewed by 7416

Abstract

Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both [...] Read more.

Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both the bacterial community and host cells. However, little is known about the fermentation of these three kinds of seaweed carbohydrates by human gut microbiota. Here, the degradation characteristics of carrageenan, agarose, alginate, and their oligosaccharides, by Bacteroides xylanisolvens, Bacteroides ovatus, and Bacteroides uniforms, isolated from human gut microbiota, are studied. Full article

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2000 KiB

Open AccessArticle

Immunomodulatory and Anti-IBDV Activities of the Polysaccharide AEX from Coccomyxa gloeobotrydiformis

by Qiang Guo, Qiang Shao, Wenping Xu, Lei Rui, Ryo Sumi, Fumio Eguchi and Zandong Li

Mar. Drugs 2017, 15(2), 36; https://doi.org/10.3390/md15020036 - 10 Feb 2017

Cited by 15 | Viewed by 5938

Abstract

A number of polysaccharides have been reported to show immunomodulatory and antiviral activities against various animal viruses. AEX is a polysaccharide extracted from the green algae, Coccomyxa gloeobotrydiformis. The aim of this study was to examine the function of AEX in regulating [...] Read more.

A number of polysaccharides have been reported to show immunomodulatory and antiviral activities against various animal viruses. AEX is a polysaccharide extracted from the green algae, Coccomyxa gloeobotrydiformis. The aim of this study was to examine the function of AEX in regulating the immune response in chickens and its capacity to inhibit the infectious bursal disease virus (IBDV), to gain an understanding of its immunomodulatory and antiviral ability. Here, preliminary immunological tests in vitro showed that the polysaccharide AEX can activate the chicken peripheral blood molecular cells’ (PBMCs) response by inducing the production of cytokines and NO, promote extracellular antigen presentation but negatively regulate intracellular antigen presentation in chicken splenic lymphocytes, and promote the proliferation of splenic lymphocytes and DT40 cells. An antiviral analysis showed that AEX repressed IBDV replication by the deactivation of viral particles or by interfering with adsorption in vitro and reduced the IBDV viral titer in the chicken bursa of Fabricius. Finally, in this study, when AEX was used as an adjuvant for the IBDV vaccine, specific anti-IBDV antibody (IgY, IgM, and IgA) titers were significantly decreased. These results indicate that the polysaccharide AEX may be a potential alternative approach for anti-IBDV therapy and an immunomodulator for the poultry industry. However, more experimentation is needed to find suitable conditions for it to be used as an adjuvant for the IBDV vaccine. Full article

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Multiple cytokines and iNOS expression were upregulated and NO production were increased by AEX in PBMCs. (A–G) PBMCs were isolated and cultured with AEX (0–100 μg/mL) or LPS (100 ng/mL) for 24 h. Then total RNA was extracted and analyzed by qRT-PCR for IFN-β, IL-1β, IL-6, TNF-α, IL-10, IL-12p40, and iNOS; (H) PBMCs were isolated and cultured with AEX (0–100 μg/mL) or LPS (100 ng/mL) for 24 h and 48 h. Then, the culture supernatants were collected and nitrite contents were determined by Griess reaction. Data represent means ± SEM from three wells per group. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001. Results are representative of two independent experiments. Full article ">Figure 2
Inflammatory cytokines and surface molecules on splenic lymphocytes were regulated by AEX. Splenic lymphocytes were isolated and cultured with AEX (0–100 μg/mL) or LPS (100 ng/mL) for 24 h. Then, total RNA was extracted and analyzed by qRT-PCR for IL-1β (A), IL-6 (B), MHC I (C), MHC II (D), CD3ε (E), CD4 (F), and CD8α (G). Data represent means ± SEM from three wells per group. * p ≤ 0.05; ** p ≤ 0.01. Results are representative of two independent experiments. Full article ">Figure 3
AEX promoted DT40 and splenic lymphocytes proliferation, but reduced peripheral blood lymphocyte proliferation in vitro. (A–C) DT40 cells, splenic lymphocytes and peripheral blood lymphocytes were cultured in 96-well plates. After being stimulated by AEX (0–250 μg/mL) or Con A (40 μg/mL) for 24 h, 48 h, and 72 h, respectively, the proliferation was examined by MTT method as described in the Materials and Methods section; (D,E) Splenic lymphocytes and peripheral blood lymphocytes were isolated and cultured with AEX (0–100 μg/mL) or LPS (100 ng/mL) for 24 h, respectively. Then, total RNA was extracted and analyzed by qRT-PCR for IL-2. Data represent means ± SEM from three wells per group. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001. Results are representative of two independent experiments. Full article ">Figure 4
AEX inhibited IBDV replication by deactivating viral particle and interfering with adsorption. (A) The Vero cells were treated with different concentrations of AEX for 24 h and cell viability was measured by MTT assay; (B) The Vero cells infected with IBDV (MOI = 1.0) were treated with different concentrations of AEX, and viral titers in the supernatant were identified by TCID50 assays on the Vero cells. PBS treatment wells served as the control; (C,D) The Vero cells infected with IBDV (MOI = 1.0) were treated with different concentrations of AEX, and immunofluorescence staining was performed using anti-IBDV antibodies. (C) Scale bar represents 100 μm; (D) IBDV positive cells number was calculated; (E) The Vero cells were incubated with IBDV (MOI = 1.0) for 1 h and treated with AEX at the indicated time points (0, 2, 4, 24 h p.i.). Viral titers in the supernatant were determined by TCID50 assays on the Vero cells at 48 h p.i. (F) The Vero cells were infected with IBDV (MOI = 1.0) via different polysaccharide treatment method (IBDV pretreatment, adsorption, and after adsorption) and viral titers in the supernatant were determined by TCID50 assays on the Vero cells at 48 h p.i. Data represent means ± SEM from three wells per group. * p ≤ 0.05; ** p ≤ 0.01. Results are representative of two independent experiments. Full article ">Figure 5
AEX inhibited IBDV replication in chicken bursa of Fabricius. SPF chickens (6 chickens per group) were oral inoculated with different concentrations of AEX (0, 62.5, 125, 250 and 500 mg/kg body weight) per day. After three days, chickens were eye-dropped with IBDV (105.5TCID50). Bursa of Fabricius were collected at 5 d.p.i. and divided into two parts. (A) Half of the bursa of Fabricius were grinded and virus titers were determined by TCID50; (B) The other half bursa of Fabricius were subjected to isolate total RNA and the expression lever of IBDV VP2 was evaluated by qRT-PCR. Data represent means ± SEM from five wells per group. * p ≤ 0.05; ** p ≤ 0.01. Results are representative of two independent experiments. Full article ">Figure 6
AEX reduced specific anti-IBDV antibody (IgY, IgM, and IgA) titers in the sera of chickens immunized with IBDV. SPF chickens (6 chickens per group) were immunized with IBDV vaccine by subcutaneous injection in the absence or presence of AEX (PBS used as control) thrice at a 14-day interval. The sera were collected (14 days after the first immunization, 7 days and 14 days after secondary immunization, and 7 days after tertiary immunization) and specific antibody (A) IgY; (B) IgM; (C) IgA were detected by ELISA. Data represent means ± SEM from five wells per group. a,b,c,d p ≤ 0.05 vs. FA. Results are representative of two independent experiments. Full article ">

2016

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1834 KiB

Open AccessArticle

Purification and Characterization of a New Alginate Lyase from Marine Bacterium Vibrio sp. SY08

by Shangyong Li, Linna Wang, Jianhua Hao, Mengxin Xing, Jingjing Sun and Mi Sun

Mar. Drugs 2017, 15(1), 1; https://doi.org/10.3390/md15010001 - 23 Dec 2016

Cited by 59 | Viewed by 6815

Abstract

Unsaturated alginate disaccharides (UADs), enzymatically derived from the degradation of alginate polymers, are considered powerful antioxidants. In this study, a new high UAD-producing alginate lyase, AlySY08, has been purified from the marine bacterium Vibrio sp. SY08. AlySY08, with a molecular weight of about [...] Read more.

Unsaturated alginate disaccharides (UADs), enzymatically derived from the degradation of alginate polymers, are considered powerful antioxidants. In this study, a new high UAD-producing alginate lyase, AlySY08, has been purified from the marine bacterium Vibrio sp. SY08. AlySY08, with a molecular weight of about 33 kDa and a specific activity of 1070.2 U/mg, showed the highest activity at 40 °C in phosphate buffer at pH 7.6. The enzyme was stable over a broad pH range (6.0–9.0) and retained about 75% activity after incubation at 40 °C for 2 h. Moreover, the enzyme was active in the absence of salt ions and its activity was enhanced by the addition of NaCl and KCl. AlySY08 resulted in an endo-type alginate lyase that degrades both polyM and polyG blocks, yielding UADs as the main product (81.4% of total products). All these features made AlySY08 a promising candidate for industrial applications in the production of antioxidants from alginate polysaccharides. Full article

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Phylogenetic tree of strain SY08 and related bacteria. The tree ID is based on a maximum parsimony analysis of the 16S rDNA sequences. The obtained 16S rDNA sequence was searched for and aligned by using the BLASTn and ClustalX programs, respectively. The phylogenetic tree was obtained by using MEGA 4.0 software. Full article ">Figure 2
SDS-PAGE analysis of purified AlySY08. The purified AlySY08 was resolved by 10% acrylamide (w/v) SDS-PAGE followed by staining with Coomassie Blue G-250. Lane M, molecular weight markers; Lane 1, purified AlySY08. Full article ">Figure 3
Effects of pH and temperature on the activity and stability of AlySY08. (a) The optimum pH for AlySY08 was determined by measuring its activity at 40 °C in 50 mM Na2HPO4-citric acid buffer (filled circle), 50 mM Na2HPO4-NaH2PO4 buffer (open circle), 50 mM Tris-HCl buffer (filled triangle) and 50 mM Gly-NaOH buffer (filled square); (b) The optimal temperature for AlySY08 was determined by measuring its activity at various temperatures (10–60 °C); (c) pH stability of AlySY08. The residual activity was measured at 40 °C in 50 mM phosphate buffer (pH 7.6) after incubation in the buffers reported above at 4 °C for 6 h; (d) Thermostability of AlySY08. The enzyme was incubated at 30 °C (filled circle), 40 °C (open rhombus), 45 °C (open square) and 50 °C (filled triangle) for various times. The residual activity was then determined at 40 °C. The activity of control (100% relative activity) is 12.6 U/mL. Full article ">Figure 4
Effect of NaCl on enzymatic activity of AlySY08. The activity of AlySY08 in the absence of NaCl was retained at 100%. All the experiments were conducted in triplicate. Full article ">Figure 5
Size-exclusion chromatography of the alginate degradation products by AlySY08. The elution volumes of the dimer (DP2), trimer (DP3), tetramer (DP4), and pentamer (DP5) are 16.1 mL, 14.9 mL, 14.1 mL and 13.7 mL, respectively. The ratios of dimers present in the degradation products were analyzed by the peak integration function on the UNICORN 5.31 software (GE Healthcare, Madison, WI, USA). Full article ">Figure 6
TLC and ESI-MS analysis of the main products of AlySY08. (a) TLC analysis. The reaction products were separated on a HPTLC plate with n-butanol/formic acid/water (2:1:1, by vol) and visualized with a diphenylamine/aniline/phosphate reagent. Lane M: standard UAOs mixture, disaccharide (DP2) and trisaccharide (DP3); Lane 0 sodium alginate; Lane 1 reaction products; (b) ESI-MS analysis of the main products by AlySY08. Full article ">

2673 KiB

Open AccessArticle

Identification of a Pro-Angiogenic Potential and Cellular Uptake Mechanism of a LMW Highly Sulfated Fraction of Fucoidan from Ascophyllum nodosum

by Nicolas Marinval, Pierre Saboural, Oualid Haddad, Murielle Maire, Kevin Bassand, Frederic Geinguenaud, Nadia Djaker, Khadija Ben Akrout, Marc Lamy de la Chapelle, Romain Robert, Olivier Oudar, Erwan Guyot, Christelle Laguillier-Morizot, Angela Sutton, Cedric Chauvierre, Frederic Chaubet, Nathalie Charnaux and Hanna Hlawaty

Mar. Drugs 2016, 14(10), 185; https://doi.org/10.3390/md14100185 - 17 Oct 2016

Cited by 36 | Viewed by 7433

Abstract

Herein we investigate the structure/function relationships of fucoidans from Ascophyllum nodosum to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size [...] Read more.

Herein we investigate the structure/function relationships of fucoidans from Ascophyllum nodosum to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size and sulfation rate of fucoidans influence their ability to induce pro-angiogenic processes independently of GAGs. We collected two fractions of fucoidans, Low and Medium Molecular Weight Fucoidan (LMWF and MMWF, respectively) by size exclusion chromatography and characterized their composition (sulfate, fucose and uronic acid) by colorimetric measurement and Raman and FT-IR spectroscopy. The high affinities of fractionated fucoidans to heparin binding proteins were confirmed by Surface Plasmon Resonance. We evidenced that LMWF has a higher pro-angiogenic (2D-angiogenesis on Matrigel) and pro-migratory (Boyden chamber) potential on HUVECs, compared to MMWF. Interestingly, in a GAG-free HUVECs model, LMWF kept a pro-angiogenic potential. Finally, to evaluate the association of LMWF-induced biological effects and its cellular uptake, we analyzed by confocal microscopy the GAGs involvement in the internalization of a fluorescent LMWF. The fluorescent LMWF was mainly internalized through HUVEC clathrin-dependent endocytosis in which GAGs were partially involved. In conclusion, a better characterization of the relationships between the fucoidan structure and its pro-angiogenic potential in GAG-free endothelial cells was required to identify an adapted fucoidan to enhance vascular repair in ischemia. Full article

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Raman and Fourrier Tansform Infrared (FT-IR) Spectroscopy analysis. Fucoidan spectra are represented in black for crude Ascophyscient (ASPHY), dark grey for the low molecular weight fucoidan (LMWF) and light grey for the medium molecular weight fucoidan (MMWF) for (A) Raman and (B) FT-IR (in H2O and in D2O). The numbers indicates the characteristics bands for polysaccharides. Full article ">Figure 2
Affinity measurement of fucoidans to SDF-1/CXCL12, RANTES/CCL5 and VEGF. The binding responses of ASPHY, MMWF, LMWF and low molecular weight heparin (LMWH) to SDF-1/CXCL12, RANTES/CCL5 and VEGF were measured by Surface Plasmon Resonance. We immobilized biotinylated SDF-1/CXCL12, RANTES/CCL5 or VEGF on streptavidin chip. Each polysaccharide was injected over flow of a BIAcore sensor chip pre-coated with streptavidin biotinylated SDF-1/CXCL12, RANTES/CCL5 or VEGF. Each set of sensorgrams was obtained by injecting increasing concentration of polysaccharides (1.2, 3.7, 11.1, 33.3, and 100 nM). The response unit (RU) was recorded as a function of time (sec) and the affinities are expressed in molar (M) with the equilibrium dissociation constant KD (Kd/Ka). LMWH was used as a positive control of sulfated polysaccharide whereas non-sulfated dextran was used as a negative control (not shown). Affinity of polysaccharides to (A) SDF-1/CXCL12; (B) RANTES/CCL5 and (C) VEGF, and their corresponding representative sensorgrams. Full article ">Figure 3
Effect of fucoidans on cell viability. The viability of HUVECs was analyzed by using MTT assay after fucoidan treatment for 24 h. The absorbance was read with a spectrophotometer (at 570 nm). HUVECs were incubated with (A) LMWF and (B) MMWF at increasing concentration (1, 10, 100, and 1000 μg/mL); (C) HUVECs were incubated 24 h with polysaccharides (dextran, LMWH, LMWF, MMWF and ASPHY) at 10 μg/mL. Values are expressed as means ± SEM (n ≥ 3). AU-Arbitrary units. * p < 0.05 versus Untreated. Full article ">Figure 4
Pro-angiogenic potential of fucoidans on GAG-free HUVECs. (A) HUVECs pre-treated or not with βDX (4-Nitrophenyl-β-d-Xylopyranoside) were seeded on Matrigel and incubated with dextran, LMWH, LMWF, MMWF or ASPHY for 6 h. The cells were then stained with Hemalun Mayer’s and photographed for analysis. Values are expressed in number of nodes per well. ** p < 0.01 LMWF or LMWH versus Untreated (all without βDX). # p < 0.05 LMWF versus Untreated (all with βDX); (B) Endogenous GAGs expression analyzed by flow cytometry on HUVECs pre-treated or not 48 h with βDX; (C) PD98059, a pharmacological inhibitor of ERK1/2 and (D) LY294002, a pharmacological inhibitor of PI3K/AKT were added in HUVEC culture, then HUVECs were seeded on Matrigel for 6 h and vascular network formation was observed as described before. Values are expressed in nodes per well (n ≥ 3). * p < 0.05 LMWF, PD98059, LY294002, LMWF + PD98059, LY294002 + LMWF versus Untreated; # p < 0.05 LMWF + PD98059 versus PD98059. Full article ">Figure 5
Pro-migratory potential of fucoidans on GAG-free HUVECs. HUVECs were seeded and incubated 24 h in the upper chamber with the polysaccharides dextran, LMWH, LMWF, MMWF or ASPHY at 10 μg/mL. The basal migration was performed in complete medium with 12% FBS. In the aim to remove the GAGs, the cells were pre-treated with βDX for 48 h, then the migration assay was performed with the same treatments as described above. The cells were fixed, stained with Mayer’s hemalun solution and counted after migration. Values are expressed as cell number per well. * p < 0.05 ASPHY versus Untreated (all without βDX); ** p < 0.01 LMWH and LMWF versus Untreated (all without βDX); $ p < 0.05 LMWH and LMWF versus Untreated (all with βDX); # p < 0.05 LMWH and LMWF and ASPHY (all without βDX) versus LMWH and LMWF and ASPHY (all with βDX). Full article ">Figure 6
LMWF-Alexa localization in HUVECs by confocal microscopy. LMWF was previously coupled with the fluorophore Alexa Fluor 555. (A) LMWF-Alexa was added in HUVEC culture medium at 10 μg/mL during 2 h at 37 °C and 4 °C. Dextran-FITC and Alexa fluor alone (Alexa) were used as negative control. Pictures were taken by confocal microscopy and the intensity of the accumulated fluorescence per cell was quantified by using specific quantification software (DAPI—blue, LMWF-Alexa—red, Dextran-FITC—green, bar = 10 μm). Values are expressed as percentage of the intensity. * p < 0.01 37 °C versus 4 °C; (B) Endogenous GAGs expression on HUVECs treated by heparinase I, II, and III and chondroitinase ABC (H/C); (C) LMWF-Alexa was incubated with HUVECs (30 min, 2 h, and 6 h) with or without heparinase I, II, and III and chondroitinase ABC (H/C) and the intensity of fluorescence per cell was measured by flow cytometry. Values are expressed as percentage of the intensity normalized on the maximum intensity reached at 2 h. The right panel shows the confocal observation. (DAPI—blue, LMWF-Alexa—red, bar = 10 μm). * p < 0.05, 2 h, and 6 h versus 30 min (all Untreated with H/C); $ p < 0.05, 6 h versus 30 min (all treated with H/C); # p < 0.05, 2 h of treated with H/C versus 2 h of Untreated. Full article ">Figure 6 Cont.
LMWF-Alexa localization in HUVECs by confocal microscopy. LMWF was previously coupled with the fluorophore Alexa Fluor 555. (A) LMWF-Alexa was added in HUVEC culture medium at 10 μg/mL during 2 h at 37 °C and 4 °C. Dextran-FITC and Alexa fluor alone (Alexa) were used as negative control. Pictures were taken by confocal microscopy and the intensity of the accumulated fluorescence per cell was quantified by using specific quantification software (DAPI—blue, LMWF-Alexa—red, Dextran-FITC—green, bar = 10 μm). Values are expressed as percentage of the intensity. * p < 0.01 37 °C versus 4 °C; (B) Endogenous GAGs expression on HUVECs treated by heparinase I, II, and III and chondroitinase ABC (H/C); (C) LMWF-Alexa was incubated with HUVECs (30 min, 2 h, and 6 h) with or without heparinase I, II, and III and chondroitinase ABC (H/C) and the intensity of fluorescence per cell was measured by flow cytometry. Values are expressed as percentage of the intensity normalized on the maximum intensity reached at 2 h. The right panel shows the confocal observation. (DAPI—blue, LMWF-Alexa—red, bar = 10 μm). * p < 0.05, 2 h, and 6 h versus 30 min (all Untreated with H/C); $ p < 0.05, 6 h versus 30 min (all treated with H/C); # p < 0.05, 2 h of treated with H/C versus 2 h of Untreated. Full article ">Figure 7
Internalization pathways of LMWF-Alexa in HUVECs analyzed by confocal microscopy. (A) HUVECs were incubated 2 h with LMWF-Alexa, fixed, permeabilized and the clathrin or caveolin-1 was revealed by immunofluorescence. A non-specific isotype of immunoglobulin was used as negative control (Isotype). The pictures were taken by confocal microscopy and the staining overlaped in merge (DAPI—blue, LMWF-Alexa—red, Clathrin—green, bar = 10 μm) high view inserts. The intensity of the fluorescence was quantified and the co-localization of markers was measured with the rate red/green represented in the histogram and dot plots. The intensity of fluorescence in HUVECs was quantified using specific software. * p < 0.05 Caveolin-1 versus Isotype; ** p < 0.01 Clathrin versus Isotype; (B) HUVECs were pre-treated or not (control) with specific inhibitors of endocytosis: Cytochalasin D (CytD-inhibits phagocytosis and micropynocytosis), Dynasore (inhibits clathrin mediated endocytosis) and Filipin (inhibits lipid raft formation) before adding LMWF-Alexa in the culture medium for 2 h. The intensity of fluorescence by cells was quantified as described above.* p < 0.05 Dynasore versus Control. Full article ">

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Open AccessArticle

Molecular Weight-Dependent Immunostimulative Activity of Low Molecular Weight Chitosan via Regulating NF-κB and AP-1 Signaling Pathways in RAW264.7 Macrophages

by Bin Zheng, Zheng-Shun Wen, Yun-Juan Huang, Mei-Sheng Xia, Xing-Wei Xiang and You-Le Qu

Mar. Drugs 2016, 14(9), 169; https://doi.org/10.3390/md14090169 - 20 Sep 2016

Cited by 42 | Viewed by 7336

Abstract

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been found to possess many important biological properties, such as antioxidant and antitumor effects. In our previous study, LMWCs were found to elicit a strong immunomodulatory response in macrophages dependent on [...] Read more.

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been found to possess many important biological properties, such as antioxidant and antitumor effects. In our previous study, LMWCs were found to elicit a strong immunomodulatory response in macrophages dependent on molecular weight. Herein we further investigated the molecular weight-dependent immunostimulative activity of LMWCs and elucidated its mechanism of action on RAW264.7 macrophages. LMWCs (3 kDa and 50 kDa of molecular weight) could significantly enhance the mRNA expression levels of COX-2, IL-10 and MCP-1 in a molecular weight and concentration-dependent manner. The results suggested that LMWCs elicited a significant immunomodulatory response, which was dependent on the dose and the molecular weight. Regarding the possible molecular mechanism of action, LMWCs promoted the expression of the genes of key molecules in NF-κB and AP-1 pathways, including IKKβ, TRAF6 and JNK1, and induced the phosphorylation of protein IKBα in RAW264.7 macrophage. Moreover, LMWCs increased nuclear translocation of p65 and activation of activator protein-1 (AP-1, C-Jun and C-Fos) in a molecular weight-dependent manner. Taken together, our findings suggested that LMWCs exert immunostimulative activity via activation of NF-κB and AP-1 pathways in RAW264.7 macrophages in a molecular weight-dependent manner and that 3 kDa LMWC shows great potential as a novel agent for the treatment of immune suppression diseases and in future vaccines. Full article

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Figure 1
Effect of LMWCs on the mRNA expression levels of COX-2 (A), IL-10 (B) and MCP-1 (C) in RAW264.7 macrophage. Each cell population (1 × 106 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 2.5, 10 and 40 μg/mL or LPS (1 μg/mL) for 24 h, respectively. The untreated cells are used as the control. These represent mean values of three independent experiments. Values are presented as means ± SD (n = 3, three independent experiments). Bars with different letters (a, b, c, d, e, f) are statistically different (p < 0.05). Full article ">Figure 2
Effects of LMWCs on the mRNA expression levels of IKKβ in RAW264.7 macrophage. Each cell population (4 × 105 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 40 μg/mL or LPS (1 μg/mL) for 12 h, respectively. The untreated cells are used as the control. These represent mean values of three independent experiments. Values are presented as means ± SD (n = 3). Bars with different letters (a, b, c, d) are statistically different (p < 0.05). Full article ">Figure 3
Effects of LMWCs on the mRNA expression levels of key molecules (TRAF6 (A), JNK1 (B)) from RAW264.7 macrophage. Each cell population (4 × 105 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 40 μg/mL or LPS (1 μg/mL) for 12 h, respectively. The untreated cells are used as the control. These represent mean values of three independent experiments. Values are presented as means ± SD (n = 3). Bars with different letters (a, b, c) are statistically different (p < 0.05). Full article ">Figure 4
Effect of LMWCs on the phosphorylation of IKBα in RAW264.7 macrophage. (A) Each cell population (4 × 105 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 40 μg/mL for 12 h, respectively (1: Control; 2: LPS; 3: 3 kDa chitosan; 4: 50 kDa chitosan); (B) Each cell population (4 × 105 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 40 μg/mL and LPS (1 μg/mL) for 12 h after pre-incubation with 20 μmol/L of wedelolactone (Wed) for 12 h, respectively (1: Control; 2: Wedelolactone (Wed); 3: Wed + LPS; 4: Wed + 3 kDa chitosan; 5: Wed + 50 kDa chitosan). The figures shown are representative of three independent experiments. These represent mean values of three independent experiments. Values are presented as means ± SD (n = 3). Bars with different letters (a, b, c, d) are statistically different (p < 0.05). Full article ">Figure 5
Effect of LMWCs on the nuclear translocation of p65 in the NF-κB pathway in RAW264.7 macrophages. Each cell population (1 × 106 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 40 μg/mL for 24 h, respectively (1: Control; 2: 50 kDa chitosan; 3: 3 kDa chitosan; 4: LPS). The figures shown are representative of three independent experiments. These represent mean values of three independent experiments. Values are presented as means ± SD (n = 3). Bars with different letters (a, b, c, d) are statistically different (p < 0.05). Full article ">Figure 6
Effect of LMWCs on activator protein-1 (AP-1) in RAW264.7 macrophages. Each cell population (1 × 106 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 40 μg/mL for 24 h, respectively (1: Control; 2: 50 kDa chitosan; 3: 3 kDa chitosan; 4: LPS). The figures shown are representative of three independent experiments. These represent mean values of three independent experiments. Values are presented as means ± SD (n = 3). Bars with different letters (a, b, c, d) are statistically different (p < 0.05). Full article ">Figure 7
Schematic diagram of the targets of LMWCs. Full article ">

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Open AccessReview

Fucoidans in Nanomedicine

by Lucas Chollet, Pierre Saboural, Cédric Chauvierre, Jean-Noël Villemin, Didier Letourneur and Frédéric Chaubet

Mar. Drugs 2016, 14(8), 145; https://doi.org/10.3390/md14080145 - 29 Jul 2016

Cited by 87 | Viewed by 11967

Abstract

Fucoidans are widespread cost-effective sulfated marine polysaccharides which have raised interest in the scientific community over last decades for their wide spectrum of bioactivities. Unsurprisingly, nanomedicine has grasped these compounds to develop innovative therapeutic and diagnostic nanosystems. The applications of fucoidans in nanomedicine [...] Read more.

Fucoidans are widespread cost-effective sulfated marine polysaccharides which have raised interest in the scientific community over last decades for their wide spectrum of bioactivities. Unsurprisingly, nanomedicine has grasped these compounds to develop innovative therapeutic and diagnostic nanosystems. The applications of fucoidans in nanomedicine as imaging agents, drug carriers or for their intrinsic properties are reviewed here after a short presentation of the main structural data and biological properties of fucoidans. The origin and the physicochemical specifications of fucoidans are summarized in order to discuss the strategy of fucoidan-containing nanosystems in Human health. Currently, there is a need for reproducible, well characterized fucoidan fractions to ensure significant progress. Full article

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Open AccessArticle

Electrospinning of Nanodiamond-Modified Polysaccharide Nanofibers with Physico-Mechanical Properties Close to Natural Skins

by Mina Mahdavi, Nafiseh Mahmoudi, Farzad Rezaie Anaran and Abdolreza Simchi

Mar. Drugs 2016, 14(7), 128; https://doi.org/10.3390/md14070128 - 7 Jul 2016

Cited by 55 | Viewed by 7972

Abstract

Electrospinning of biopolymers has gained significant interest for the fabrication of fibrous mats for potential applications in tissue engineering, particularly for wound dressing and skin regeneration. In this study, for the first time, we report successful electrospinning of chitosan-based biopolymers containing bacterial cellulous [...] Read more.

Electrospinning of biopolymers has gained significant interest for the fabrication of fibrous mats for potential applications in tissue engineering, particularly for wound dressing and skin regeneration. In this study, for the first time, we report successful electrospinning of chitosan-based biopolymers containing bacterial cellulous (33 wt %) and medical grade nanodiamonds (MND) (3 nm; up to 3 wt %). Morphological studies by scanning electron microscopy showed that long and uniform fibers with controllable diameters from 80 to 170 nm were prepared. Introducing diamond nanoparticles facilitated the electrospinning process with a decrease in the size of fibers. Fourier transform infrared spectroscopy determined hydrogen bonding between the polymeric matrix and functional groups of MND. It was also found that beyond 1 wt % MND, percolation networks of nanoparticles were formed which affected the properties of the nanofibrous mats. Uniaxial tensile testing of the woven mats determined significant enhancement of the strength (from 13 MPa to 25 MP) by dispersion of 1 wt % MND. The hydrophilicity of the mats was also remarkably improved, which was favorable for cell attachment. The water vapor permeability was tailorable in the range of 342 to 423 µg·Pa⁻¹·s⁻¹·m⁻¹. The nanodiamond-modified mats are potentially suitable for wound healing applications. Full article

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Full article ">Figure 1
Effect of medical grade nanodiamonds (MND) on the morphology and size distribution of electrospun fibers: (a) chitosan/bacterial cellulose (CS/BC) without MND; (c) contain 1%; (e) 2% and (g) 3% MND particles, respectively. (b), (d), (f) and (h) show the fiber diameter distribution diagrams of each specimen. Full article ">Figure 2
Formation of large nanoparticle clusters upon electrospinning. The concentration of MND (%) is (a) 2 and (b) 3. Full article ">Figure 3
Fourier transform infrared (FT-IR) spectrum of (a) CS/BC polymer; (b) the nanocomposite fiber containing 3% MND; and (c) pristine MND. Full article ">Figure 4
Effect of diamond particles on the hydrophilicity of electrospun CS/BC mats. Full article ">Figure 5
Stress-strain curves of electrospun mats containing different amounts of diamond nanoparticles. Full article ">Figure 6
Weight change per unit of area of the mats versus time for CS/BC mats containing different amounts of MND. Full article ">Figure 7
Cell viability of CS/BC mats dependent on the MND content at two incubated times. Full article ">

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Open AccessArticle

Anticancer Effect of Fucoidan on DU-145 Prostate Cancer Cells through Inhibition of PI3K/Akt and MAPK Pathway Expression

by Gang-Sik Choo, Hae-Nim Lee, Seong-Ah Shin, Hyeong-Jin Kim and Ji-Youn Jung

Mar. Drugs 2016, 14(7), 126; https://doi.org/10.3390/md14070126 - 7 Jul 2016

Cited by 55 | Viewed by 8554

Abstract

In this study, we showed that PI3K/Akt signaling mediates fucoidan’s anticancer effects on prostate cancer cells, including suppression of proliferation. Fucoidan significantly decreased viability of DU-145 cancer cells in a concentration-dependent manner as shown by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The drug also significantly [...] Read more.

In this study, we showed that PI3K/Akt signaling mediates fucoidan’s anticancer effects on prostate cancer cells, including suppression of proliferation. Fucoidan significantly decreased viability of DU-145 cancer cells in a concentration-dependent manner as shown by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The drug also significantly increased chromatin condensation, which indicates apoptosis, in a concentration-dependent manner as shown by DAPI (4′,6-diamidino-2-phenylindole) staining. Fucoidan increased expression of Bax, cleaved poly-ADP ribose polymerase and cleaved caspase-9, and decreased of the Bcl-2, p-Akt, p-PI3K, p-P38, and p-ERK in a concentration-dependent manner. In vivo, fucoidan (at 5 and 10 mg/kg) significantly decreased tumor volume, and increased apoptosis as assessed by the TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, confirming the tumor inhibitory effect. The drug also increased expression of p-Akt and p-ERK as shown by immunohistochemistry staining. Therefore, fucoidan may be a promising cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human prostate cancer cells. Full article

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416 KiB

Open AccessArticle

Toxicological Evaluation of Low Molecular Weight Fucoidan in Vitro and in Vivo

by Pai-An Hwang, Ming-De Yan, Hong-Ting Victor Lin, Kuan-Lun Li and Yen-Chang Lin

Mar. Drugs 2016, 14(7), 121; https://doi.org/10.3390/md14070121 - 24 Jun 2016

Cited by 46 | Viewed by 7764

Abstract

For a long time, fucoidan has been well known for its pharmacological activities, and recently low molecular weight fucoidan (LMF) has been used in food supplements and pharmaceutical products. In the present study, LMF was extracted from Laminaria japonica by enzyme hydrolysis. The [...] Read more.

For a long time, fucoidan has been well known for its pharmacological activities, and recently low molecular weight fucoidan (LMF) has been used in food supplements and pharmaceutical products. In the present study, LMF was extracted from Laminaria japonica by enzyme hydrolysis. The toxicity of LMF in mouse and rat models was determined by many methods, such as total arsenic content, bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus assay. The present findings showed that LMF at 5000 μg/mL exhibited no mutagenicity. It also produced no formatting disruption of red blood cells in vivo. At 2000 mg/kg BW/day there were no toxicological indications. LMF is expected to be used as a safe food supplement. Full article

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Open AccessArticle

Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

by Liliana A. Caetano, António J. Almeida and Lídia M.D. Gonçalves

Mar. Drugs 2016, 14(5), 90; https://doi.org/10.3390/md14050090 - 11 May 2016

Cited by 82 | Viewed by 10329

Abstract

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal [...] Read more.

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. Full article

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Open AccessFeature PaperReview

Marine Origin Polysaccharides in Drug Delivery Systems

by Matias J. Cardoso, Rui R. Costa and João F. Mano

Mar. Drugs 2016, 14(2), 34; https://doi.org/10.3390/md14020034 - 5 Feb 2016

Cited by 219 | Viewed by 17265

Abstract

Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and [...] Read more.

Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. Full article

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Full article ">Figure 1
Interrelations of marine origin polysaccharides in drug delivery systems for advances therapies and applications. Full article ">Figure 2
Marine origin polysaccharides categorized by electrostatic nature and carboxylated/sulfated structure. Full article ">Figure 3
Optical microscope images of alginate microspheres before (A) and after (B) ultrasound exposure. Reprinted with permission from [<a href="#B51-marinedrugs-14-00034" class="html-bibr">51</a>], Copyright © 2014 American Chemical Society. Full article ">Figure 4
Transmission electron microscopy (TEM) micrograph of chitosan/carrageenan nanoparticles (A). Ovalbumin release profile from chitosan-carrageenan nanoparticles (B). Adapted with permission from [<a href="#B108-marinedrugs-14-00034" class="html-bibr">108</a>], Copyright © 2009 Wiley Periodicals, Inc. Full article ">Figure 5
TEM image of chitosan/fucoidan nanoparticles (A). Gentamicin release kinetics from chitosan/fucoidan particles (B). Adapted with permission from [<a href="#B119-marinedrugs-14-00034" class="html-bibr">119</a>], Copyright © 2014 distributed under a Creative Commons Attribution License. Full article ">

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Open AccessReview

Fucoidan as a Potential Therapeutic for Major Blinding Diseases—A Hypothesis

by Alexa Klettner

Mar. Drugs 2016, 14(2), 31; https://doi.org/10.3390/md14020031 - 3 Feb 2016

Cited by 36 | Viewed by 8380

Abstract

Fucoidan is a heterogeneous group of sulfated polysaccharide with a high content of l-fucose, which can be extracted from brown algae and marine invertebrates. It has many beneficial biological activities that make fucoidan an interesting candidate for therapeutic application in a variety [...] Read more.

Fucoidan is a heterogeneous group of sulfated polysaccharide with a high content of l-fucose, which can be extracted from brown algae and marine invertebrates. It has many beneficial biological activities that make fucoidan an interesting candidate for therapeutic application in a variety of diseases. Age-related macular degeneration and diabetic retinopathy are major causes for vision loss and blindness in the industrialized countries and increasingly in the developing world. Some of the characteristics found in certain fucoidans, such as its anti-oxidant activity, complement inhibition or interaction with the Vascular Endothelial Growth factor, which would be of high interest for a potential application of fucoidan in age-related macular degeneration or diabetic retinopathy. However, the possible usage of fucoidan in ophthalmological diseases has received little attention so far. In this review, biological activities of fucoidan that could be of interest regarding these diseases will be discussed. Full article

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1534 KiB

Open AccessArticle

Structural and Immunological Activity Characterization of a Polysaccharide Isolated from Meretrix meretrix Linnaeus

by Li Li, Heng Li, Jianying Qian, Yongfeng He, Jialin Zheng, Zhenming Lu, Zhenghong Xu and Jinsong Shi

Mar. Drugs 2016, 14(1), 6; https://doi.org/10.3390/md14010006 - 29 Dec 2015

Cited by 15 | Viewed by 5948

Abstract

Polysaccharides from marine clams perform various biological activities, whereas information on structure is scarce. Here, a water-soluble polysaccharide MMPX-B2 was isolated from Meretrix meretrix Linnaeus. The proposed structure was deduced through characterization and its immunological activity was investigated. MMPX-B2 consisted of d-glucose [...] Read more.

Polysaccharides from marine clams perform various biological activities, whereas information on structure is scarce. Here, a water-soluble polysaccharide MMPX-B2 was isolated from Meretrix meretrix Linnaeus. The proposed structure was deduced through characterization and its immunological activity was investigated. MMPX-B2 consisted of d-glucose and d-galctose residues at a molar ratio of 3.51:1.00. The average molecular weight of MMPX-B2 was 510 kDa. This polysaccharide possessed a main chain of (1→4)-linked-α-d-glucopyranosyl residues, partially substituted at the C-6 position by a few terminal β-d-galactose residues or branched chains consisting of (1→3)-linked β-d-galactose residues. Preliminary immunological tests in vitro showed that MMPX-B2 could stimulate the murine macrophages to release various cytokines, and the structure-activity relationship was then established. The present study demonstrated the potential immunological activity of MMPX-B2, and provided references for studying the active ingredients in M. meretrix. Full article

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Full article ">Figure 1
Purification of MMPX-B2. (a) Elution profile of crude polysaccharides by DEAE-52 cellulose; (b) Purification profile of MMPX-B by Superdex 200; (c) HP-GPC profile of MMPX-B2. Full article ">Figure 2
GC profile of MMPX-B2 with acid hydrolysis and acetylation. (A) d-glucose; (B) d-galactose; (C) internal standard inositol. Full article ">Figure 3
FT-IR spectrum of MMPX-B2. Full article ">Figure 4
NMR spectra of MMPX-B2. (a) 13C-NMR; (b) 1H-NMR. Full article ">Figure 5
Proposed structural model of MMPX-B2. Full article ">Figure 6
Effects of MMPX-B2 on macrophages-mediated immunity in vitro. (a) Nitrate accumulation; (b) TNF-α; (c) IL-1β; (d) IL-6. ** is representative of p < 0.01 and *** is representative of p < 0.001, when compared to the control group. Full article ">

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Open AccessArticle

Characterization and Comparison of the Structural Features, Immune-Modulatory and Anti-Avian Influenza Virus Activities Conferred by Three Algal Sulfated Polysaccharides

by Lin Song, Xiaolin Chen, Xiaodong Liu, Fubo Zhang, Linfeng Hu, Yang Yue, Kecheng Li and Pengcheng Li

Mar. Drugs 2016, 14(1), 4; https://doi.org/10.3390/md14010004 - 29 Dec 2015

Cited by 65 | Viewed by 7693

Abstract

Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, [...] Read more.

Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, the monosaccharide composition and the sulfated contents of three extracted SPs were determined, and their structures were characterized by Fourier transformation infrared spectroscopy. In addition, biological activity analysis showed that all three SPs had immune-modulatory activity both in vitro and in vivo, and SPs from S. qingdaoense had the best effect. Further bioassays showed that three SPs could not only enhance the immunity level stimulated by inactivated avian influenza virus (AIV) in vivo but also significantly inhibited the activity of activated AIV (H9N2 subtype) in vitro. G. filicina SP exhibited the strongest anti-AIV activity. These results revealed the variations in structural features and bioactivities among three SPs and indicated the potential adjuvants for immune-enhancement and anti-AIV. Full article

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Graphical abstract

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Full article ">Figure 1
FT-IR spectra of three extracted sulfated polysaccharides. GFP, Grateloupia filicina; UPP, Ulva Pertusa; SQP, Sargassum qingdaoens. Full article ">Figure 2
Mouse spleen cell proliferation effects of GFP, UPP and SQP. Mock treated with PBS instead of polysaccharides as a negative control. Values with different letters in the same column (a–d) are significantly different (p < 0.05) from each other. Data are shown as the Mean + SD and are fully representative of the individual experiment. Full article ">Figure 3
Avian influenza virus (AIV)-specific antibody titer detection. Kunming mice were immunized with an AIV vaccine and polysaccharides, following the prime-boost vaccination programme (days 0 and 14), respectively. (A) GFP; (B) UPP; (C) SQP. Values with different letters in the same column (a–d) are significantly different (p < 0.05) from each other. Data are shown as the Mean + SD and are fully representative of an individual experiment. Full article ">Figure 4
Cytokine production stimulating effect of GFP, UPP and SQP. Kunming mice were immunized with an AIV vaccine and polysaccharides, and sera were collected on day 28 after two immunizations to detect the cytokines IFN-γ (A) and IL-4 (B). Values with different letters in the same column (a–d) are significantly different (p < 0.05) from each other. Data are shown as the Mean + SD and are fully representative for the individual experiment. Full article ">Figure 5
T-cell subpopulation tests. The blood cells of the treated mice were collected and analyzed with flow cytometry. (A) CD3+CD4+. (B) CD3+CD8+. Values with different letters in the same column (a–d) are significantly different (p < 0.05) from each other. Data are shown as the Mean + SD and are fully representative of the individual experiment. Full article ">Figure 6
Haemagglutination test (HA) of the cell culture and relative expression of H9N2. Antiviral activity in vitro was measured with a HA test (A) and RT-PCR (B). Data from samples without polysaccharides were used as a basic control. Values with different letters in the same column (a–c) are significantly different (p < 0.05) from each other. Data are shown as the Mean + SD and are fully representative of the individual experiment. Full article ">

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Open AccessArticle

Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis

by Oualid Haddad, Erwan Guyot, Nicolas Marinval, Fabien Chevalier, Loïc Maillard, Latifa Gadi, Christelle Laguillier-Morizot, Olivier Oudar, Angela Sutton, Nathalie Charnaux and Hanna Hlawaty

Mar. Drugs 2015, 13(11), 6588-6608; https://doi.org/10.3390/md13116588 - 28 Oct 2015

Cited by 8 | Viewed by 6579

Abstract

Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of [...] Read more.

Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases. Full article

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951 KiB

Open AccessArticle

Salt Effect on the Antioxidant Activity of Red Microalgal Sulfated Polysaccharides in Soy-Bean Formula

by Ariela Burg and Levy-Ontman Oshrat

Mar. Drugs 2015, 13(10), 6425-6439; https://doi.org/10.3390/md13106425 - 20 Oct 2015

Cited by 12 | Viewed by 6361

Abstract

Sulfated polysaccharides produced by microalgae, which are known to exhibit various biological activities, may potentially serve as natural antioxidant sources. To date, only a few studies have examined the antioxidant bioactivity of red microalgal polysaccharides. In this research, the effect of different salts [...] Read more.

Sulfated polysaccharides produced by microalgae, which are known to exhibit various biological activities, may potentially serve as natural antioxidant sources. To date, only a few studies have examined the antioxidant bioactivity of red microalgal polysaccharides. In this research, the effect of different salts on the antioxidant activities of two red microalgal sulfated polysaccharides derived from Porphyridium sp. and Porphyridium aerugineum were studied in a soy bean-based infant milk formula. Salt composition and concentration were both shown to affect the polysaccharides’ antioxidant activity. It can be postulated that the salt ions intefer with the polysaccharide chains’ interactions and alter their structure, leading to a new three-dimensional structure that better exposes antiooxidant sites in comparison to the polysaccharide without salt supplement. Among the cations that were studied, Ca²⁺ had the strongest enhancement effect on antioxidant activities of both polysaccharides. Understanding the effect of salts on polysaccharides’ stucture, in addition to furthering knowledge on polysaccharide bioactivities, may also shed light on the position of the antioxidant active sites. Full article

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Figure 1
Antioxidant activity of PS1 and PS2 in soy bean milk formula following addition of KO2. CMDA was measured by thiobarbitoric acid (TBA) method. All treatments contained 0.5 g formula, 0.35 mM KO2, with or without 0.075/0.15% w/v of either PS1 or PS2 polysaccharides. Values are expressed as mean ± SD, n = 3. Full article ">Figure 2
Polysaccharide antioxidant activity induction by sodium salts. CMDA was measured by TBA method. Experimental setup included 0.5 g formula with 0.35 mM KO2, 0.15% w/v polysaccharide and various sodium salts at two different concentrations, in a final volume of 10 mL. Values represent the mean of at least 3 repeats; Maximum standard deviation equals 5%. Full article ">Figure 3
Polysaccharide antioxidant activity induction by potassium salts. CMDA was measured by TBA method. Experimental setup included 0.5 g formula with 0.35 mM KO2, 0.15% w/v polysaccharide and various potassium salts at two different concentrations, in a final volume of 10 mL. Values represent the mean of at least 3 repeats; Maximum standard deviation equals 8%. Full article ">Figure 4
Polysaccharide antioxidant activity induction by divalent cation salts. CMDA was measured by TBA test. Experimental setup included 0.5 g formula with 0.35 mM KO2, 0.15% w/v polysaccharide, and various divalent salts at two different concentrations, in a final volume of 10 mL. Values represent the mean of at least 3 repeats. Maximum standard deviation equals 8%. Full article ">

548 KiB

Open AccessCommunication

Immunostimulative Activity of Low Molecular Weight Chitosans in RAW264.7 Macrophages

by Ning Wu, Zheng-Shun Wen, Xing-Wei Xiang, Yan-Na Huang, Yang Gao and You-Le Qu

Mar. Drugs 2015, 13(10), 6210-6225; https://doi.org/10.3390/md13106210 - 30 Sep 2015

Cited by 53 | Viewed by 7058

Abstract

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been reported to exert many biological activities, such as antioxidant and antitumor effects. However, complex and molecular weight dependent effects of chitosan remain controversial and the mechanisms that mediate these complex [...] Read more.

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been reported to exert many biological activities, such as antioxidant and antitumor effects. However, complex and molecular weight dependent effects of chitosan remain controversial and the mechanisms that mediate these complex effects are still poorly defined. This study was carried out to investigate the immunostimulative effect of different molecular weight chitosan in RAW264.7 macrophages. Our data suggested that two LMWCs (molecular weight of 3 kDa and 50 kDa) both possessed immunostimulative activity, which was dependent on dose and, at the higher doses, also on the molecular weight. LMWCs could significantly enhance the the pinocytic activity, and induce the production of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon-γ (IFN-γ), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in a molecular weight and concentration-dependent manner. LMWCs were further showed to promote the expression of the genes including iNOS, TNF-α. Taken together, our findings suggested that LMWCs elicited significantly immunomodulatory response through up-regulating mRNA expression of proinflammatory cytokines and activated RAW264.7 macrophage in a molecular weight- and concentration-dependent manner. Full article

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Figure 1
Effects of low molecular weight chitosans (LMWCs) on the cell viability of RAW264.7 macrophage. Each cell population (2 × 104 cells/well) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 2.5, 10 and 40 μg/mL for 24 h, respectively. Values are means ± SD (n = 3). Bars with no letters are not statistically different (p > 0.05). Full article ">Figure 2
Effects of LMWCs on the pinocytic activity of RAW264.7 macrophage. Each cell population (1 × 104 cells/well) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 2.5, 10 and 40 μg/mL for 24 h, respectively. Values are means ± SD (n = 3). Bars with different letters (a, b, c, d, e, f) are statistically different (p < 0.05). Full article ">Figure 3
Effects of LMWCs on the production of tumor necrosis factor α (TNF-α) (A), interferon-γ (IFN-γ) (B) and interleukin 6 (IL-6) (C) from RAW264.7 macrophage. Each cell population (1 × 106 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 2.5, 10 and 40 μg/mL for 24 h, respectively. Values are means ± SD (n = 3). Bars with different letters (a, b, c, d, e, f) are statistically different (p < 0.05). Full article ">Figure 3 Cont.
Effects of LMWCs on the production of tumor necrosis factor α (TNF-α) (A), interferon-γ (IFN-γ) (B) and interleukin 6 (IL-6) (C) from RAW264.7 macrophage. Each cell population (1 × 106 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 2.5, 10 and 40 μg/mL for 24 h, respectively. Values are means ± SD (n = 3). Bars with different letters (a, b, c, d, e, f) are statistically different (p < 0.05). Full article ">Figure 4
Effect of LMWCs on Nitric oxide (NO) production and activities of inducible nitric oxide synthase (iNOS) in RAW264.7 macrophage. Each cell population (1 × 106 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 2.5, 10 and 40 μg/mL for 24 h, respectively. Values are means ± SD (n = 3). Bars with different letters (a, b, c, d, e, f) are statistically different (p < 0.05). Full article ">Figure 5
Effect of LMWCs on the mRNA expression levels of TNF-α and iNOS in RAW264.7 macrophage. Each cell population (1 × 106 cells/mL) was treated with LMWCs (3 kDa and 50 kDa) at the indicated concentrations of 2.5, 10 and 40 μg/mL for 24 h, respectively. Values are means ± SD (n = 3). Bars with different letters (a, b, c, d, e, f) are statistically different (p < 0.05). Full article ">

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Open AccessArticle

Alginate-Derived Oligosaccharide Inhibits Neuroinflammation and Promotes Microglial Phagocytosis of β-Amyloid

by Rui Zhou, Xu-Yang Shi, De-Cheng Bi, Wei-Shan Fang, Gao-Bin Wei and Xu Xu

Mar. Drugs 2015, 13(9), 5828-5846; https://doi.org/10.3390/md13095828 - 16 Sep 2015

Cited by 71 | Viewed by 9121

Abstract

Alginate from marine brown algae has been widely applied in biotechnology. In this work, the effects of alginate-derived oligosaccharide (AdO) on lipopolysaccharide (LPS)/β-amyloid (Aβ)-induced neuroinflammation and microglial phagocytosis of Aβ were studied. We found that pretreatment of BV2 microglia with AdO prior to [...] Read more.

Alginate from marine brown algae has been widely applied in biotechnology. In this work, the effects of alginate-derived oligosaccharide (AdO) on lipopolysaccharide (LPS)/β-amyloid (Aβ)-induced neuroinflammation and microglial phagocytosis of Aβ were studied. We found that pretreatment of BV2 microglia with AdO prior to LPS/Aβ stimulation led to a significant inhibition of production of nitric oxide (NO) and prostaglandin E₂ (PGE₂), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and secretion of proinflammatory cytokines. We further demonstrated that AdO remarkably attenuated the LPS-activated overexpression of toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB in BV2 cells. In addition to the impressive inhibitory effect on neuroinflammation, we also found that AdO promoted the phagocytosis of Aβ through its interaction with TLR4 in microglia. Our results suggested that AdO exerted the inhibitory effect on neuroinflammation and the promotion effect on microglial phagocytosis, indicating its potential as a nutraceutical or therapeutic agent for neurodegenerative diseases, particularly Alzheimer’s disease (AD). Full article

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1074 KiB

Open AccessArticle

The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes

by Loredana Stabili, Roberto Schirosi, Maria Giovanna Parisi, Stefano Piraino and Matteo Cammarata

Mar. Drugs 2015, 13(8), 5276-5296; https://doi.org/10.3390/md13085276 - 19 Aug 2015

Cited by 56 | Viewed by 9339

Abstract

The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, [...] Read more.

The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones’ mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. Full article

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Figure 1
Actinia equina mucus composition: (A) water content and dried weight; (B) organic and inorganic residuals. Full article ">Figure 2
SDS-PAGE analysis of Actinia equina mucus. Panel A: Molecular weight standards furnished by Fermentas. Molecular weights (kDa) of standard proteins are on left; Panel B: A. equina total mucus; (C) Actinia equina different molecular weight fractions from total mucus extract obtained by membrane filtration system (pore size: 10 kDa). SDS-PAGE 15% acrylamide gel stained with Coomassie Blue R-250. Lane 1: Fraction >10 kDa named “U” (Upper), Lane 2: Standard Low sigma, Lane 3: Fraction <10 kDa. Named “D” (Lower); (D) Micro plate lysis assay carried out against Rabbit erythrocytes (RRBCs) in TBS buffer. Hemolysis is evidenced by free hemoglobin, when the erythrocytes are not lysed a central pellet of erythrocytes is visible on the well center. Lower fraction (D) showing lysis until dilution of 1:64, Upper fraction (U) showing lysis until dilution of 1:2048, Control experiment (Ce) with RRBCs and buffer. Full article ">Figure 3
Lysozyme-like activity of Actinia equina mucus. (A) Standard assay on Petri dish inoculated with Micrococcus lysodeikticus cell walls to detect the lysozyme-like activity of A. equina mucus; (B) Effect of the pH on the lysozyme-like activity of A. equina mucus. Columns are mean values (n = 20) (vertical bars ± Standard Deviation); (C) Effect of the ionic strength on the lysozyme-like activity of mucus. Columns are mean values (n = 20) (vertical bars ± Standard Deviation); (D) Effect of the incubation temperature on the lysozyme-like activity of mucus. Columns are mean values (n = 20) (vertical bars ± Standard Deviation). Full article ">Figure 4
(A) Light Microscopic observation of Human erythromyeloblastoid leukemia (K562) cells treated with A. equine mucus crude extract. The target cell lysis was also determined by trypan blue exclusion test. Bar: 25 μm; (B) Control cell observed in the absence of mucus Bar. 25 μm; (C) Colorimetric assay of A. equina mucus extract on human chronic myelogenous leukemia cells K562 (Cytotoxic detection Kit. Boehringer Mannheim, Mannheim, Germany). Lactate dehydrogenase release into the supernatant was used to calculate the percentage of target cell lysis. Full article ">Figure 5
(A) High performance liquid chromatography separation of A. equina mucus components. The first plot shows profile of HPLC analysis of the crude mucus extract. Green arrows 1 and 2 indicate the isolated peaks at 12.5 and 14.5 min. Insert shows HPLC profiles of bovine serum albumin (BSA-66 kDa), chimotrypsinogen (25 kDa) and ribonuclease (13.7 kDa) used as standards separated on a molecular weight exclusion column BioSuite 250 (10 microns; Waters, Milford, CT, USA). The second plot shows the purification profiles of the high molecular weight fraction (u = upper) and low molecular weight fraction (d = lower) previously separated via centrifugation system on 10 kDa membrane. Red arrow indicate peak 2 detected at 14.5 min post HPLC start running; (B) Lytic activity detected in microplate toward rabbit erythrocytes of peaks 1 and 2 (Ce: Control experiment). Full article ">

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Open AccessReview

Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications

by Randy Chi Fai Cheung, Tzi Bun Ng, Jack Ho Wong and Wai Yee Chan

Mar. Drugs 2015, 13(8), 5156-5186; https://doi.org/10.3390/md13085156 - 14 Aug 2015

Cited by 977 | Viewed by 31580

Abstract

Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as [...] Read more.

Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as versatile biomaterials because of their non-toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the recent research, trends and prospects in chitosan. Some special pharmaceutical and biomedical applications are also highlighted. Full article

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466 KiB

Open AccessArticle

Laminarin from Irish Brown Seaweeds Ascophyllum nodosum and Laminaria hyperborea: Ultrasound Assisted Extraction, Characterization and Bioactivity

by Shekhar U. Kadam, Colm P. O'Donnell, Dilip K. Rai, Mohammad B. Hossain, Catherine M. Burgess, Des Walsh and Brijesh K. Tiwari

Mar. Drugs 2015, 13(7), 4270-4280; https://doi.org/10.3390/md13074270 - 10 Jul 2015

Cited by 216 | Viewed by 13134

Abstract

Ultrasound assisted extraction (UAE), purification, characterization and antioxidant activity of laminarin from Irish brown seaweeds Ascophyllum nodosum and Laminarina hyperborea were investigated. UAE was carried out using 60% ultrasonic power amplitude and 0.1 M hydrochloric acid for 15 min. Separately, solid-liquid extraction was [...] Read more.

Ultrasound assisted extraction (UAE), purification, characterization and antioxidant activity of laminarin from Irish brown seaweeds Ascophyllum nodosum and Laminarina hyperborea were investigated. UAE was carried out using 60% ultrasonic power amplitude and 0.1 M hydrochloric acid for 15 min. Separately, solid-liquid extraction was carried in an orbital shaker using 0.1 M hydrochloric acid at 70 °C for 2.5 h. UAE with hydrochloric acid resulted in the highest concentration of laminarin, 5.82% and 6.24% on dry weight basis from A. nodosum and L. hyperborea, respectively. Purification of all extracts was carried out using molecular weight cut off dialysis at 10 kDa. Characterization of the laminarin fraction was carried out using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Antioxidant activity of A. nodosum and L. hyperborea extracts had 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition levels of 93.23% and 87.57%, respectively. Moreover, these extracts have shown inihibition of bacterial growth of Staphylcoccus aureus, Listeria monocytogenes, Escherichia coli and Salmonella typhimurium. Full article

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1879 KiB

Open AccessArticle

Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion

by Elene Sapharikas, Anna Lokajczyk, Anne-Marie Fischer and Catherine Boisson-Vidal

Mar. Drugs 2015, 13(7), 4156-4170; https://doi.org/10.3390/md13074156 - 30 Jun 2015

Cited by 18 | Viewed by 7798

Abstract

Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a [...] Read more.

Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p < 0.05) and a five-fold increase in chemotaxis in Boyden chambers (p < 0.05). Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p < 0.05). MMP9 activity in monocyte supernatants was significantly enhanced by fucoidan (p < 0.05). Finally, Western blot analysis of fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p < 0.01). Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment. Full article

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Graphical abstract

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Full article ">Figure 1
Fucoidan enhances monocyte adhesion to gelatin, and their migration. (A) Representative results obtained with PBMC after 30 min, with or without 24 h of fucoidan pretreatment; (B) Monocyte adhesion (in white, control monocytes, in black, monocytes incubated with 10 μg/mL fucoidan; (C) Representative results for migration of isolated PBMC treated with or without fucoidan (4 h) towards 100 ng/mL MCP-1; (D) Migratory cell numbers in five independent fields; (E) Representative monocyte transmigration (18 h) with or without fucoidan pretreatment (30 min); (F) Transmigratory cell numbers in five independent fields. Three to five independent donors. * p < 0.05; ** p < 0.01. Full article ">Figure 2
Impact of fucoidan on adhesion molecule and CCR2 receptor expression: PBMC were treated for 30 min or 24 h with (black bars) or without fucoidan (white bars). (A) Percentage of monocytes positive for alpha M expression; (B) Percentage of beta 2-positive cells; (C) Percentage of alpha 4-positive cells; (D) Percentage of beta 1-positive cells; (E) Percentage of CCR2-positive cells (4 independent donors). Full article ">Figure 3
Impact of fucoidan on monocyte MMP9 expression (gelatinolytic activity): (A) Representative gelatin zymography of culture supernatant of monocytes treated with or without fucoidan for 30 min; (B) MMP9 gelanitolytic activity; (C) MMP2 gelatinolytic activity. Three independent donors; * p < 0.05 Full article ">Figure 4
ERK and p38 signaling pathway involvement in fucoidan-treated monocyte migration: (A) Representative Western blot illustrating phosphorylation of ERK1/2 and P38 when PBMC were treated with or without fucoidan (in the presence or absence of PD98059 or SB203580) for 30 min; (B) Quantitative analysis of ERK phosphorylation; (C) Quantitative analysis of p38 phosphorylation. Results are represented relative to the corresponding control, with with independent donors; (D) Representative fields showing migratory cells treated as in A; (E) Migratory cell numbers in five independent fields. * p < 0.05; ** p < 0.01; *** p < 0.001 compared to control. Four independent donors. Full article ">Figure 5
Schematic overview of the effect of fucoidan on monocyte migration. Fucoidan bound to the cell membrane enhances MCP-1 interaction with its receptor CCR2. This interaction leads to phosphorylation of ERK1/2 and p38 and activates MM9 secretion. PD98059 and SB203580 inhibit this phosphorylation, leading to reduced monocyte migration. Full article ">

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Open AccessReview

Seaweed Hydrocolloid Production: An Update on Enzyme Assisted Extraction and Modification Technologies

by Nanna Rhein-Knudsen, Marcel Tutor Ale and Anne S. Meyer

Mar. Drugs 2015, 13(6), 3340-3359; https://doi.org/10.3390/md13063340 - 27 May 2015

Cited by 258 | Viewed by 18682

Abstract

Agar, alginate, and carrageenans are high-value seaweed hydrocolloids, which are used as gelation and thickening agents in different food, pharmaceutical, and biotechnological applications. The annual global production of these hydrocolloids has recently reached 100,000 tons with a gross market value just above US$ [...] Read more.

Agar, alginate, and carrageenans are high-value seaweed hydrocolloids, which are used as gelation and thickening agents in different food, pharmaceutical, and biotechnological applications. The annual global production of these hydrocolloids has recently reached 100,000 tons with a gross market value just above US$ 1.1 billion. The techno-functional properties of the seaweed polysaccharides depend strictly on their unique structural make-up, notably degree and position of sulfation and presence of anhydro-bridges. Classical extraction techniques include hot alkali treatments, but recent research has shown promising results with enzymes. Current methods mainly involve use of commercially available enzyme mixtures developed for terrestrial plant material processing. Application of seaweed polysaccharide targeted enzymes allows for selective extraction at mild conditions as well as tailor-made modifications of the hydrocolloids to obtain specific functionalities. This review provides an update of the detailed structural features of κ-, ι-, λ-carrageenans, agars, and alginate, and a thorough discussion of enzyme assisted extraction and processing techniques for these hydrocolloids. Full article

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Open AccessArticle

Production of Chondroitin Sulphate from Head, Skeleton and Fins of Scyliorhinus canicula By-Products by Combination of Enzymatic, Chemical Precipitation and Ultrafiltration Methodologies

by María Blanco, Javier Fraguas, Carmen G. Sotelo, Ricardo I. Pérez-Martín and José Antonio Vázquez

Mar. Drugs 2015, 13(6), 3287-3308; https://doi.org/10.3390/md13063287 - 27 May 2015

Cited by 37 | Viewed by 7305

Abstract

This study illustrates the optimisation of the experimental conditions of three sequential steps for chondroitin sulphate (CS) recovery from three cartilaginous materials of Scyliorhinus canicula by-products. Optimum conditions of temperature and pH were first obtained for alcalase proteolysis of head cartilage (58 °C/pH [...] Read more.

This study illustrates the optimisation of the experimental conditions of three sequential steps for chondroitin sulphate (CS) recovery from three cartilaginous materials of Scyliorhinus canicula by-products. Optimum conditions of temperature and pH were first obtained for alcalase proteolysis of head cartilage (58 °C/pH 8.5/0.1% (v/w)/10 h of hydrolysis). Then, similar optimal conditions were observed for skeletons and fin materials. Enzymatic hydrolysates were subsequently treated with a combination of alkaline hydroalcoholic saline solutions in order to improve the protein hydrolysis and the selective precipitation of CS. Ranges of 0.53–0.64 M (NaOH) and 1.14–1.20 volumes (EtOH) were the levels for optimal chemical treatment depending on the cartilage origin. Finally, selective purification and concentration of CS and protein elimination of samples obtained from chemical treatment, was assessed by a combination of ultrafiltration and diafiltration (UF-DF) techniques at 30 kDa. Full article

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Full article ">Figure 1
Kinetics of cartilage hydrolysis from Scyliorhinus canicula heads using alcalase in each one of the experimental conditions defined in <a href="#marinedrugs-13-03287-t001" class="html-table">Table 1</a>. The experimental data (symbols) were fitted to the Weibull Equation (4) (continuous line). Full article ">Figure 2
Predicted response surfaces by empirical equations summarized in <a href="#marinedrugs-13-03287-t003" class="html-table">Table 3</a> corresponding to the combined effect of pH and T on the different dependent variables evaluated for the study of head-cartilages proteolysis by alcalase. Full article ">Figure 3
Enzymatic hydrolysis at two pH levels for different cartilages from S. canicula wastes (left). To the right, long hydrolysis at the best pH selected are additionally shown. Experimental data were fitted to the Weibull Equation (4). (A) Fins; (B) Heads and (C) Skeletons. Full article ">Figure 4
Predicted response surfaces by empirical equations summarized in <a href="#marinedrugs-13-03287-t007" class="html-table">Table 7</a> corresponding to the combined effect of NaOH and EtOH on the selective treatment of CS from hydrolysate cartilages of S. canicula. Full article ">Figure 5
UF-DF process for CS purification from S. canicula cartilages of three origins at 30 kDa. Top: Concentration of retained protein (○) and CS (●) in linear relation with the factor of volumetric concentration (fc) showing experimental data (points) and theoretical profiles corresponding to a completely retained solute (discontinuous line). Bottom: Progress of protein (○) and CS (●) retention with the increase of diavolume from DF process (D). Equation (6) was used to fit the experimental data. Error bars are the confidence intervals (α = 0.05; n = 2). Full article ">

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Open AccessArticle

Antidiabetic Activity of Differently Regioselective Chitosan Sulfates in Alloxan-Induced Diabetic Rats

by Ronge Xing, Xiaofei He, Song Liu, Huahua Yu, Yukun Qin, Xiaolin Chen, Kecheng Li, Rongfeng Li and Pengcheng Li

Mar. Drugs 2015, 13(5), 3072-3090; https://doi.org/10.3390/md13053072 - 15 May 2015

Cited by 22 | Viewed by 5900

Abstract

The present study investigated and compared the hypoglycemic activity of differently regioselective chitosan sulfates in alloxan-induced diabetic rats. Compared with the normal control rats, significantly higher blood glucose levels were observed in the alloxan-induced diabetic rats. The differently regioselective chitosan sulfates exhibited hypoglycemic [...] Read more.

The present study investigated and compared the hypoglycemic activity of differently regioselective chitosan sulfates in alloxan-induced diabetic rats. Compared with the normal control rats, significantly higher blood glucose levels were observed in the alloxan-induced diabetic rats. The differently regioselective chitosan sulfates exhibited hypoglycemic activities at different doses and intervals, especially 3-O-sulfochitosan (3-S). The major results are as follows. First, 3,6-di-O-sulfochitosan and 3-O-sulfochitosan exhibited more significant hypoglycemic activities than 2-N-3, 6-di-O-sulfochitosan and 6-O-sulfochitosan. Moreover, 3-S-treated rats showed a more significant reduction of blood glucose levels than those treated by 3,6-di-O-sulfochitosan. These results indicated that –OSO₃⁻ at the C3-position of chitosan is a key active site. Second, 3-S significantly reduced the blood glucose levels and regulated the glucose tolerance effect in the experimental rats. Third, treatment with 3-S significantly increased the plasma insulin levels in the experimental diabetic rats. A noticeable hypoglycemic activity of 3-S in the alloxan-induced diabetic rats was shown. Clinical trials are required in the future to confirm the utility of 3-S. Full article

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Full article ">Figure 1
FTIR of H2,3,6-S (1) chitosan; (2) H2,3,6-S under dichloroacetic acid; (3) H2,3,6-S under formic acid. Full article ">Figure 2
FTIR of 2-phthalimido-chitosan under 90 °C; 1: FTIR of 2-phthalimido-chitosan under 3.5 h; 2: FTIR of 2-phthalimido-chitosan under 3.0 h; 3: FTIR of 2-phthalimido-chitosan under 2.0 h. Full article ">Figure 3
FTIR of 3,6-S; 3: Eliminating the phthalimido group under 3 h; 6: Eliminating the phthalimido group under 6 h; 10: Eliminating the phthalimido group under 10 h; 16: Eliminating the phthalimido group under 16 h. Full article ">Figure 4
FTIR of 3-S. Full article ">Figure 5
FTIR of 6-S; 1: Chitosan; 2: Cu-chitosan chelation; 3: Cu- sulfated chitoan chelation under formic acid; 4: Cu- sulfated chitoan chelation without formic acid. Full article ">Figure 6
FTIR of L2,3,6-S; 1: Chitosan; 2: L2,3,6-S under traditional heating; 3: L2,3,6-S under microwave radiation (800W). Full article ">Figure 7
Hypoglycemic effects of 3-S on the fasting blood glucose levels of normal rats during GTT, each value shown in mean ± S.E.; n = 10, number of animals in each group. Full article ">

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Open AccessReview

Marine Polysaccharides from Algae with Potential Biomedical Applications

by Maria Filomena De Jesus Raposo, Alcina Maria Bernardo De Morais and Rui Manuel Santos Costa De Morais

Mar. Drugs 2015, 13(5), 2967-3028; https://doi.org/10.3390/md13052967 - 15 May 2015

Cited by 493 | Viewed by 23590

Abstract

There is a current tendency towards bioactive natural products with applications in various industries, such as pharmaceutical, biomedical, cosmetics and food. This has put some emphasis in research on marine organisms, including macroalgae and microalgae, among others. Polysaccharides with marine origin constitute one [...] Read more.

There is a current tendency towards bioactive natural products with applications in various industries, such as pharmaceutical, biomedical, cosmetics and food. This has put some emphasis in research on marine organisms, including macroalgae and microalgae, among others. Polysaccharides with marine origin constitute one type of these biochemical compounds that have already proved to have several important properties, such as anticoagulant and/or antithrombotic, immunomodulatory ability, antitumor and cancer preventive, antilipidaemic and hypoglycaemic, antibiotics and anti-inflammatory and antioxidant, making them promising bioactive products and biomaterials with a wide range of applications. Their properties are mainly due to their structure and physicochemical characteristics, which depend on the organism they are produced by. In the biomedical field, the polysaccharides from algae can be used in controlled drug delivery, wound management, and regenerative medicine. This review will focus on the biomedical applications of marine polysaccharides from algae. Full article

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2607 KiB

Open AccessArticle

Alginate Hydrogels Coated with Chitosan for Wound Dressing

by Maria Cristina Straccia, Giovanna Gomez D'Ayala, Ida Romano, Adriana Oliva and Paola Laurienzo

Mar. Drugs 2015, 13(5), 2890-2908; https://doi.org/10.3390/md13052890 - 11 May 2015

Cited by 128 | Viewed by 13713

Abstract

In this work, a coating of chitosan onto alginate hydrogels was realized using the water-soluble hydrochloride form of chitosan (CH-Cl), with the dual purpose of imparting antibacterial activity and delaying the release of hydrophilic molecules from the alginate matrix. Alginate hydrogels with different [...] Read more.

In this work, a coating of chitosan onto alginate hydrogels was realized using the water-soluble hydrochloride form of chitosan (CH-Cl), with the dual purpose of imparting antibacterial activity and delaying the release of hydrophilic molecules from the alginate matrix. Alginate hydrogels with different calcium contents were prepared by the internal setting method and coated by immersion in a CH-Cl solution. Structural analysis by cryo-scanning electron microscopy was carried out to highlight morphological alterations due to the coating layer. Tests in vitro with human mesenchymal stromal cells (MSC) were assessed to check the absence of toxicity of CH-Cl. Swelling, stability in physiological solution and release characteristics using rhodamine B as the hydrophilic model drug were compared to those of relative uncoated hydrogels. Finally, antibacterial activity against Escherichia coli was tested. Results show that alginate hydrogels coated with chitosan hydrochloride described here can be proposed as a novel medicated dressing by associating intrinsic antimicrobial activity with improved sustained release characteristics. Full article

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Open AccessArticle

λ-Carrageenan Suppresses Tomato Chlorotic Dwarf Viroid (TCDVd) Replication and Symptom Expression in Tomatoes

by Jatinder S. Sangha, Saveetha Kandasamy, Wajahatullah Khan, Navratan Singh Bahia, Rudra P. Singh, Alan T. Critchley and Balakrishnan Prithiviraj

Mar. Drugs 2015, 13(5), 2875-2889; https://doi.org/10.3390/md13052875 - 8 May 2015

Cited by 36 | Viewed by 9108

Abstract

The effect of carrageenans on tomato chlorotic dwarf viroid (TCDVd) replication and symptom expression was studied. Three-week-old tomato plants were spray-treated with iota(ɩ)-, lambda(λ)-, and kappa(κ)-carrageenan at 1 g·L⁻¹ and inoculated with TCDVd after 48 h. The λ-carrageenan significantly suppressed viroid symptom [...] Read more.

The effect of carrageenans on tomato chlorotic dwarf viroid (TCDVd) replication and symptom expression was studied. Three-week-old tomato plants were spray-treated with iota(ɩ)-, lambda(λ)-, and kappa(κ)-carrageenan at 1 g·L⁻¹ and inoculated with TCDVd after 48 h. The λ-carrageenan significantly suppressed viroid symptom expression after eight weeks of inoculation, only 28% plants showed distinctive bunchy-top symptoms as compared to the 82% in the control group. Viroid concentration was reduced in the infected shoot cuttings incubated in λ-carrageenan amended growth medium. Proteome analysis revealed that 16 tomato proteins were differentially expressed in the λ-carrageenan treated plants. Jasmonic acid related genes, allene oxide synthase (AOS) and lipoxygenase (LOX), were up-regulated in λ-carrageenan treatment during viroid infection. Taken together, our results suggest that λ-carrageenan induced tomato defense against TCDVd, which was partly jasmonic acid (JA) dependent, and that it could be explored in plant protection against viroid infection. Full article

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Figure 1
Symptoms of TCDVd infection in tomatoes. Three-week-old tomato plants were inoculated with 10 μL of TCDVd sap and the symptoms were observed at 28 dpi. Infected plants (RT-PCR confirmed) were stunted with bunchy top symptoms, smaller fruits and fewer roots. Full article ">Figure 2
Suppressive effect of λ-carrageenan in tomatoes against TCDVd infection. (a) Percentage of plants showing typical TCDVd symptoms in control and λ-carrageenan (λ-Carr) treated plants. Data represent the mean of percent infected plants from three independent trials (Mean ± SEM, n = 36); (b) Relative intensity of TCDVd bands visualized on agarose gel and quantified with ImageJ software in controls and λ-carrageenan (λ-Carr) treated plants at 35 dpi (Mean ± SEM, n = 10). Full article ">Figure 3
Plant height and last internode length of infected and healthy tomato plants one month after TCDVd inoculation. Bars represent control (black) and λ-carrageenan (λ-Carr, white). Data represent Mean ± SEM (n = 36 for healthy plants and n = 12 plants for infected plants), student’s t-test at p < 0.05. Full article ">Figure 4
Effect of carrageenans on TCDVd multiplication in tomato determined by RT-PCR. TCDVd concentration in the leaf samples from infected shoots was determined at 0, 7, 14, and 21 days post carrageenan treatment (λ-carrageenan (λ-Carr), ɩ-carrageenan (ɩ-Carr), κ-carrageenan (κ-Carr)) with RT-PCR using TCDVd specific primers. The bands were visualized on agarose gel. Full article ">Figure 5
A general proteome map of tomato leaves with TCDVd infection in λ-carrageenan treatment. Proteins were separated first on an IPG strip (pH 4.0–7.0) and then based on molecular weight (kDA) on a 12% SDS-PAGE. Differentially expressed proteins are marked, red circled were increased whereas green circled were decreased. Full article ">Figure 6
Expression of defense response genes encoding allene oxide synthase (AOS), lipoxygenase (LOX) and pathogenesis related protein 1 (PR1), in tomatoes during TCDVd infection. The expression of genes was analyzed at 0 (AOS-0, LOX-0 and PR1-0) and 7 (AOS-7, LOX-7 and PR1-7) dpi in control and λ-carrageenan (λ-Carr) treated plants. Values with “*” are significantly different (p < 0.05). (Mean ± S.E., n = 3). Full article ">

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Open AccessReview

Perspective on the Use of Sulfated Polysaccharides from Marine Organisms as a Source of New Antithrombotic Drugs

by Paulo A. S. Mourão

Mar. Drugs 2015, 13(5), 2770-2784; https://doi.org/10.3390/md13052770 - 6 May 2015

Cited by 93 | Viewed by 8048

Abstract

Thromboembolic diseases are increasing worldwide and always require anticoagulant therapy. We still need safer and more secure antithrombotic drugs than those presently available. Sulfated polysaccharides from marine organisms may constitute a new source for the development of such drugs. Investigation of these compounds [...] Read more.

Thromboembolic diseases are increasing worldwide and always require anticoagulant therapy. We still need safer and more secure antithrombotic drugs than those presently available. Sulfated polysaccharides from marine organisms may constitute a new source for the development of such drugs. Investigation of these compounds usually attempts to reproduce the therapeutic effects of heparin. However, we may need to follow different routes, focusing particularly in the following aspects: (1) defining precisely the specific structures required for interaction of these sulfated polysaccharides with proteins of the coagulation system; (2) looking for alternative mechanisms of action, distinct from those of heparin; (3) identifying side effects (mostly pro-coagulant action and hypotension rather than bleeding) and preparing derivatives that retain the desired antithrombotic action but are devoid of side effects; (4) considering that sulfated polysaccharides with low anticoagulant action on in vitro assays may display potent effects on animal models of experimental thrombosis; and finally (5) investigating the antithrombotic effect of these sulfated polysaccharides after oral administration or preparing derivatives that may achieve this effect. If these aspects are successfully addressed, sulfated polysaccharides from marine organisms may conquer the frontier of antithrombotic therapy and open new avenues for treatment or prevention of thromboembolic diseases. Full article

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539 KiB

Open AccessArticle

Employment of Marine Polysaccharides to Manufacture Functional Biocomposites for Aquaculture Feeding Applications

by Marina Paolucci, Gabriella Fasulo and Maria Grazia Volpe

Mar. Drugs 2015, 13(5), 2680-2693; https://doi.org/10.3390/md13052680 - 29 Apr 2015

Cited by 12 | Viewed by 5289

Abstract

In this study, polysaccharides of marine origin (agar, alginate and κ-carrageenan) were used to embed nutrients to fabricate biocomposites to be employed in animal feeding. The consistency of biocomposites in water has been evaluated up to 14 days, by several methods: swelling, nutrient [...] Read more.

In this study, polysaccharides of marine origin (agar, alginate and κ-carrageenan) were used to embed nutrients to fabricate biocomposites to be employed in animal feeding. The consistency of biocomposites in water has been evaluated up to 14 days, by several methods: swelling, nutrient release and granulometric analysis. Biocomposites were produced with varying percentages of nutrients (5%–25%) and polysaccharides (1%–2%–3%). All possible biopolymer combinations were tested in order to select those with the best network strength. The best performing biocomposites were those manufactured with agar 2% and nutrients 10%, showing the lowest percentage of water absorption and nutrient release. Biocomposites made of agar 2% and nutrients 10% were the most stable in water and were therefore used to analyze their behavior in water with respect to the release of quercetin, a phenolic compound with demonstrated high antibacterial and antioxidant activities. The leaching of such molecules in water was therefore employed as a further indicator of biocomposite water stability. Altogether, our results confirm the suitability of agar as a binder for biocomposites and provide a positive contribution to aquaculture. Full article

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Open AccessArticle

Seaweed Polysaccharides (Laminarin and Fucoidan) as Functional Ingredients in Pork Meat: An Evaluation of Anti-Oxidative Potential, Thermal Stability and Bioaccessibility

by Natasha C. Moroney, Michael N. O'Grady, Sinéad Lordan, Catherine Stanton and Joseph P. Kerry

Mar. Drugs 2015, 13(4), 2447-2464; https://doi.org/10.3390/md13042447 - 20 Apr 2015

Cited by 66 | Viewed by 9574

Abstract

The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) [...] Read more.

The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L₁₀₀), F₁₀₀ and L/F_100,300, and bioaccessibility post in vitro digestion (L/F₃₀₀), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork. Full article

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Full article ">Figure 1
Lipid oxidation in 25% longissimus thoracis et lumborum (LTL) pork muscle homogenates following the addition of L, F or L/F and storage for up to 4 h at 4 °C. * Subscripts 3 and 6 denote concentrations in mg/mL. abcd Mean values (± standard deviation error bars) bearing different superscripts are significantly different, p < 0.05. Full article ">Figure 2
Absorbance spectra of oxymyoglobin (OxyMb) alone and following the addition of F1 (* Subscript 1 denotes concentration in mg/mL) and storage for up to 8 days at 4 °C. Full article ">Figure 3
Free radical scavenging activity (DPPH) of L, F or L/F in fresh and cooked minced longissimus thoracis et lumborum (LTL) pork muscle stored for 20 h at ~20 °C. * Subscripts 100 and 300 denote concentrations in mg/g. ab Within each treatment, mean values (± standard deviation error bars) bearing different superscripts are significantly different, p < 0.05. Comparing wx fresh and yz cooked LTL pork muscle treatments to their respective controls, mean values bearing different superscripts are significantly different, p < 0.05. ( <img alt="Marinedrugs 13 02447 i001" src="/marinedrugs/marinedrugs-13-02447/article_deploy/html/images/marinedrugs-13-02447-i001.png"/>), fresh; ( <img alt="Marinedrugs 13 02447 i002" src="/marinedrugs/marinedrugs-13-02447/article_deploy/html/images/marinedrugs-13-02447-i002.png"/>), cooked. Full article ">Figure 4
Free radical scavenging activity (DPPH) of L, F or L/F in digested cooked minced longissimus thoracis et lumborum (LTL) pork muscle stored for 20 h at ~20 °C. * Subscripts 100 and 300 denote concentrations in mg/g. abc Mean values (± standard deviation error bars) bearing different superscripts are significantly different, p < 0.05. Full article ">

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Open AccessArticle

Chitin-Lignin Material as a Novel Matrix for Enzyme Immobilization

by Jakub Zdarta, Łukasz Klapiszewski, Marcin Wysokowski, Małgorzata Norman, Agnieszka Kołodziejczak-Radzimska, Dariusz Moszyński, Hermann Ehrlich, Hieronim Maciejewski, Allison L. Stelling and Teofil Jesionowski

Mar. Drugs 2015, 13(4), 2424-2446; https://doi.org/10.3390/md13042424 - 20 Apr 2015

Cited by 68 | Viewed by 10190

Abstract

Innovative materials were made via the combination of chitin and lignin, and the immobilization of lipase from Aspergillus niger. Analysis by techniques including FTIR, XPS and ¹³C CP MAS NMR confirmed the effective immobilization of the enzyme on the surface of [...] Read more.

Innovative materials were made via the combination of chitin and lignin, and the immobilization of lipase from Aspergillus niger. Analysis by techniques including FTIR, XPS and ¹³C CP MAS NMR confirmed the effective immobilization of the enzyme on the surface of the composite support. The electrokinetic properties of the resulting systems were also determined. Results obtained from elemental analysis and by the Bradford method enabled the determination of optimum parameters for the immobilization process. Based on the hydrolysis reaction of para-nitrophenyl palmitate, a determination was made of the catalytic activity, thermal and pH stability, and reusability. The systems with immobilized enzymes were found to have a hydrolytic activity of 5.72 mU, and increased thermal and pH stability compared with the native lipase. The products were also shown to retain approximately 80% of their initial catalytic activity, even after 20 reaction cycles. The immobilization process, using a cheap, non-toxic matrix of natural origin, leads to systems with potential applications in wastewater remediation processes and in biosensors. Full article

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Open AccessReview

The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

by Garry Kerch

Mar. Drugs 2015, 13(4), 2158-2182; https://doi.org/10.3390/md13042158 - 13 Apr 2015

Cited by 98 | Viewed by 14043

Abstract

Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in [...] Read more.

Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. Full article

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Open AccessArticle

Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-Defined Repeating Unit from Sea Cucumber

by Mingyi Wu, Li Xu, Longyan Zhao, Chuang Xiao, Na Gao, Lan Luo, Lian Yang, Zi Li, Lingyun Chen and Jinhua Zhao

Mar. Drugs 2015, 13(4), 2063-2084; https://doi.org/10.3390/md13042063 - 13 Apr 2015

Cited by 59 | Viewed by 11964

Abstract

Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif [...] Read more.

Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants. Full article

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Figure 1
FT-IR spectrum of the sulfated fucan from sea cucumber. Full article ">Figure 2
1H (A,B) and 13C (C) one-dimensional NMR spectra at 500 MHz of the sulfated fucan from H. edulis. The spectra were recorded at 300 K for samples in D2O solution. Chemical shifts are relative to external trimethylsilylpropionic acid at 0 ppm. The residual water has been suppressed by pre-saturation. The anomeric signals assigned by 1H/13C HSQC (see <a href="#marinedrugs-13-02063-f005" class="html-fig">Figure 5</a>) are labeled A–E in the sulfated fucan. Expansion of the 4.9–5.6 ppm region of the 1H spectrum is shown in the inset in (A). The integrals were listed under the anomeric signals (B). Full article ">Figure 3
1H/1H COSY spectra of the sulfated fucans from H. edulis (A) and L. grisea (B). The spectra were recorded at 300 K for samples in D2O solution. Chemical shifts are relative to external trimethylsilylpropionic acid at 0 ppm. The residual water has been suppressed by pre-saturation. The anomeric signals assigned by 1H/13C HSQC (see <a href="#marinedrugs-13-02063-f005" class="html-fig">Figure 5</a>) are labeled A–E in the sulfated fucans. Full article ">Figure 4
Expansions of the TOCSY (A,B) and ROESY (C,D) spectra of two sulfated fucans from H. edulis and L. grisea (B,D).The TOCSY spectra (A,B)show some cross-peaks used in the assignment of the fucose residue, especially positions bearing sulfate esters. The ROESY spectra (B,D) show ROEs, the sequence-defining A1–B3, B1–C3, C1–D2, D1–A3 and E1–D4. The five fucose residues in the repeating unit are marked A–E as described in the legend of <a href="#marinedrugs-13-02063-f006" class="html-fig">Figure 6</a>. Full article ">Figure 5
1H/13C HSQC (A,B) and HMBC (C,D) spectra of two sulfated fucans from two sea cucumbers H. edulis (A,C) and L. grisea (B,D). The assignments were based on TOCSY and COSY spectra. The anomeric signals were identified by the characteristic carbon chemical shifts and are marked A–E. The HMBC spectra (C,D) also show the sequence-defining A1–B3, B1–C3, C1–D2, D/D'1–A3 and E1–D4. The five fucose residues in the repeating unit are marked A–E as described in the legends of <a href="#marinedrugs-13-02063-f006" class="html-fig">Figure 6</a>. Full article ">Figure 6
Proposed regular repeating units of sulfated fucan isolated from two sea cucumbers H. edulis (A) and L. grisea (B). The five fucose residues in the repeating unit are marked A–E as described in the legends. Full article ">Figure 7
Inhibitory effects of the sulfated fucans, heparin, low molecular weight heparin (LMWH) and dermatan sulfate (DS) on thrombin mediated by heparin cofactor II. (A) Shows the time course of thrombin inhibition. HCII (~1 μM) was incubated with thrombin (20 NIH/mL) in the presence of 30 μL (625 ng/mL) samples at 37 °C. After 2 min, 30 μL of 4.5 mM CS-01 (38) was added, the residual thrombin activity was recorded by absorbance at 405 nm; (B) Shows the dependence on the sulfated polysaccharide concentration for thrombin inactivation in the presence of HCII. The reaction mixtures were as described in (A), except that different concentrations of sulfated polysaccharides were used. Results are shown as means of duplicates. See <a href="#marinedrugs-13-02063-t004" class="html-table">Table 4</a> for IC50 values. Full article ">Figure 8
Inhibitory effects of the sulfated fucans, heparin, LMWH and DS on thrombin in the presence of antithrombin. (A) Shows the time course of thrombin inhibition. Mixed samples of 30 μL of polysaccharides (625 ng/mL) and 30 μL of 0.25 IU/mL AT were incubated at 37 °C for 2 min, and 30 μL of 24 NIH/mL IIa was then added. After incubation for 2 min, 30 μL of 1.25 mM CS-01 (38) was added, the residual factor IIa activity was recorded by absorbance at 405 nm; (B) Shows the dependence on the sulfated polysaccharide concentration for thrombin inactivation mediated by AT. The reaction mixtures were as described in (A), except that different concentrations of sulfated polysaccharides were used. Results are shown as means of duplicates. See <a href="#marinedrugs-13-02063-t004" class="html-table">Table 4</a> for IC50 values. Full article ">Figure 9
Inhibitory effects of the sulfated fucans, heparin, LMWH and DS on factor Xa in the presence of antithrombin. (A) Shows the time course of Xa inhibition. Mixed samples of 30 μL of polysaccharides (625 ng/mL) and 30 μL of 1 IU/mL AT were incubated at 37 °C for 2 min, and 30 μL of 8 μg/mL bovine Xa was then added. After incubation for 1 min, 30 μL of 1.20 mM CS-11(65) was added, the residual Xa activity was recorded by absorbance at 405 nm; (B) Shows the dependence on the sulfated polysaccharide concentration for Xa inactivation in the presence of AT. The reaction mixtures were as described in (A), except that different concentrations of sulfated polysaccharides were used. Results are shown as means of duplicates. See <a href="#marinedrugs-13-02063-t004" class="html-table">Table 4</a> for IC50 values. Full article ">Figure 10
Profile of the platelet aggregation induced by the sea cucumber polysaccharides: the sulfated fucan from L. grisea (A); the sulfated fucan and fucosylated glycosaminoglycan from H. edulis (B). The profile showed that the sulfated fucans from sea cucumber do not cause platelets to aggregate at several concentrations. Full article ">

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Open AccessArticle

Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice

by Tse-Hung Huang, Yi-Han Chiu, Yi-Lin Chan, Ya-Huang Chiu, Hang Wang, Kuo-Chin Huang, Tsung-Lin Li, Kuang-Hung Hsu and Chang-Jer Wu

Mar. Drugs 2015, 13(4), 1882-1900; https://doi.org/10.3390/md13041882 - 3 Apr 2015

Cited by 85 | Viewed by 12111

Abstract

Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and [...] Read more.

Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs. Full article

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Figure 1
Effects of fucoidan on body weight and lung mass in the LLC xenografted mouse model. At the 25th day, mice were sacrificed and examined for final gains of body weights (A) and lung masses (B); (C) The treatment protocol of fucoidan in tumor-bearing mice. Mice were fed orally with water or low- or high-dose of fucoidan (1 or 3 mg/mice) seven days before tumor implantation. Data are expressed as means ± SD (n = 6 mice per group; two independent experiments). Asterisk (*) stands for a significant difference when compared with the control group (p < 0.05). Full article ">Figure 2
Fucoidan reduces growth of lung tumor in mice. (A) Lung, pleural and bronchus tissues. 3 × 105 LLC cells were injected by tail vein in mice. Mice were sacrificed at the 25th day. The solid tumors (indicated by arrows) were spotted on multiple sites in mice; (B) Lungs were subjected to histological analysis (H&E stain) for determining metastasis. Six representative samples are shown. Full article ">Figure 3
Expression of metastatic proteins in sera of tumor bearing mice treated with fucoidan. (A) Western blot analyses of VEGF from representative mice. Expression levels of VEGF normalized to β-actin (B). Asterisk (*) indicates a significant difference (p value < 0.05) when compared to the con group. Pound (#) indicates a significant difference (p value < 0.05) when compared to TB-Con. Full article ">Figure 4
Expression of metastatic proteins in lung tissues of tumor bearing mice treated with fucoidan. (A) Western blot analyses of MMP-2, NF-κB and VEGF (from representative samples); (B) Protein expression levels that are quantified and expressed as a fold-change relative to the control. Asterisk (*) indicates a significant difference (p value < 0.05) when compared to the con group. Pound (#) indicates a significant difference (p value < 0.05) when compared to TB-Con; (C) Immunofluorescence analysis for lung tumors treated and untreated (TB-Con) with fucoidan. Images are shown at 200× magnification. Full article ">Figure 4 Cont.
Expression of metastatic proteins in lung tissues of tumor bearing mice treated with fucoidan. (A) Western blot analyses of MMP-2, NF-κB and VEGF (from representative samples); (B) Protein expression levels that are quantified and expressed as a fold-change relative to the control. Asterisk (*) indicates a significant difference (p value < 0.05) when compared to the con group. Pound (#) indicates a significant difference (p value < 0.05) when compared to TB-Con; (C) Immunofluorescence analysis for lung tumors treated and untreated (TB-Con) with fucoidan. Images are shown at 200× magnification. Full article ">Figure 5
Effects of fucoidan on cell viability in African green monkey kidney Vero and mouse Lewis lung carcinoma cells. Cells were incubated in a culture medium containing various concentrations of fucoidan for 24 h. After the treatment, cell viability was determined by the MTS assay. Values relative to that of vehicle control were determined, in which the cell viability of control is set as 100%. Data (each value is an average of at least three independent experiments (six tests)) are presented as mean ± SEM. Asterisk (*) indicates a significant difference (p value < 0.05) relative to the vehicle-treated cells. Full article ">Figure 6
Suppression of migration and invasion of lung adenocarcinoma cells by fucoidan. (A) Representative photographs of three independent experiments, showing a dose-dependent inhibition of migration after treatment of fucoidan (24 h). Images of wound closures (10× magnification); (B) Black dotted lines indicate the wound edge. The cell-free areas invaded by cells (across the black dotted lines) were quantified by three random fields as shown in the lower panels; (C) The invasiveness of the LLC cells were quantified by counting the stained cells that invade into the porous polycarbonate membrane; (D) Invasiveness of the LLC cells treated with fucoidan. The LLC cells were pretreated with fucoidan for 24 h and then seeded onto the transwell chamber. Photographs were taken by an inverted microscope with 10× magnification. Data were derived from three independent experiments and presented as mean ± SEM. * p < 0.05, ** p < 0.001, *** p < 0.0001 when compared to the vehicle-treated cells. Full article ">Figure 7
Enzymatic activities of MMP-2 and MMP-9 in the LLC cell lines treated with fucoidan. (A) The activity of MMPs was determined by the gelatinase zymography, in which the bright zones stand for gelatin digested; (B) The MMPs activity was quantified by measuring the band intensity in the zymography. Data were derived from three independent experiments and presented as mean ± SEM. * p < 0.05, ** p < 0.001, *** p < 0.0001 when compared to the vehicle-treated cells. Full article ">

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Open AccessReview

Recent Advances in Exopolysaccharides from Paenibacillus spp.: Production, Isolation, Structure, and Bioactivities

by Tzu-Wen Liang and San-Lang Wang

Mar. Drugs 2015, 13(4), 1847-1863; https://doi.org/10.3390/md13041847 - 1 Apr 2015

Cited by 89 | Viewed by 9331

Abstract

This review provides a comprehensive summary of the most recent developments of various aspects (i.e., production, purification, structure, and bioactivity) of the exopolysaccharides (EPSs) from Paenibacillus spp. For the production, in particular, squid pen waste was first utilized successfully to produce [...] Read more.

This review provides a comprehensive summary of the most recent developments of various aspects (i.e., production, purification, structure, and bioactivity) of the exopolysaccharides (EPSs) from Paenibacillus spp. For the production, in particular, squid pen waste was first utilized successfully to produce a high yield of inexpensive EPSs from Paenibacillus sp. TKU023 and P. macerans TKU029. In addition, this technology for EPS production is prevailing because it is more environmentally friendly. The Paenibacillus spp. EPSs reported from various references constitute a structurally diverse class of biological macromolecules with different applications in the broad fields of pharmacy, cosmetics and bioremediation. The EPS produced by P. macerans TKU029 can increase in vivo skin hydration and may be a new source of natural moisturizers with potential value in cosmetics. However, the relationships between the structures and activities of these EPSs in many studies are not well established. The contents and data in this review will serve as useful references for further investigation, production, structure and application of Paenibacillus spp. EPSs in various fields. Full article

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746 KiB

Open AccessReview

Stability of Chitosan—A Challenge for Pharmaceutical and Biomedical Applications

by Emilia Szymańska and Katarzyna Winnicka

Mar. Drugs 2015, 13(4), 1819-1846; https://doi.org/10.3390/md13041819 - 1 Apr 2015

Cited by 621 | Viewed by 18058

Abstract

Chitosan—one of the natural multifunctional polymers—due to its unique and versatile biological properties is regarded as a useful compound in medical and pharmaceutical technology. Recently, considerable research effort has been made in order to develop safe and efficient chitosan products. However, the problem [...] Read more.

Chitosan—one of the natural multifunctional polymers—due to its unique and versatile biological properties is regarded as a useful compound in medical and pharmaceutical technology. Recently, considerable research effort has been made in order to develop safe and efficient chitosan products. However, the problem of poor stability of chitosan-based systems restricts its practical applicability; thus, it has become a great challenge to establish sufficient shelf-life for chitosan formulations. Improved stability can be assessed by controlling the environmental factors, manipulating processing conditions (e.g., temperature), introducing a proper stabilizing compound, developing chitosan blends with another polymer, or modifying the chitosan structure using chemical or ionic agents. This review covers the influence of internal, environmental, and processing factors on the long-term stability of chitosan products. The aim of this paper is also to highlight the latest developments which enable the physicochemical properties of chitosan-based applications to be preserved upon storage. Full article

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1375 KiB

Open AccessArticle

Morphological and Proteomic Analyses Reveal that Unsaturated Guluronate Oligosaccharide Modulates Multiple Functional Pathways in Murine Macrophage RAW264.7 Cells

by Xu Xu, De-Cheng Bi, Chao Li, Wei-Shan Fang, Rui Zhou, Shui-Ming Li, Lian-Li Chi, Min Wan and Li-Ming Shen

Mar. Drugs 2015, 13(4), 1798-1818; https://doi.org/10.3390/md13041798 - 30 Mar 2015

Cited by 34 | Viewed by 7908

Abstract

Alginate is a natural polysaccharide extracted from various species of marine brown algae. Alginate-derived guluronate oligosaccharide (GOS) obtained by enzymatic depolymerization has various pharmacological functions. Previous studies have demonstrated that GOS can trigger the production of inducible nitric oxide synthase (iNOS)/nitric oxide (NO), [...] Read more.

Alginate is a natural polysaccharide extracted from various species of marine brown algae. Alginate-derived guluronate oligosaccharide (GOS) obtained by enzymatic depolymerization has various pharmacological functions. Previous studies have demonstrated that GOS can trigger the production of inducible nitric oxide synthase (iNOS)/nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor (TNF)-α by macrophages and that it is involved in the nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase signaling pathways. To expand upon the current knowledge regarding the molecular mechanisms associated with the GOS-induced immune response in macrophages, comparative proteomic analysis was employed together with two-dimensional electrophoresis (2-DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and Western blot verification. Proteins showing significant differences in expression in GOS-treated cells were categorized into multiple functional pathways, including the NF-κB signaling pathway and pathways involved in inflammation, antioxidant activity, glycolysis, cytoskeletal processes and translational elongation. Moreover, GOS-stimulated changes in the morphologies and actin cytoskeleton organization of RAW264.7 cells were also investigated as possible adaptations to GOS. This study is the first to reveal GOS as a promising agent that can modulate the proper balance between the pro- and anti-inflammatory immune responses, and it provides new insights into pharmaceutical applications of polysaccharides. Full article

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Graphical abstract

Graphical abstract
Full article ">Figure 1
The infrared (IR) spectrum of polyguluronic acid (PG). The spectrum was run in KBr pellets with 1 mg of sample and 200 mg of KBr. Full article ">Figure 2
The electrospray ionization mass spectrometry (ESI-MS) of guluronate oligosaccharide (GOS). The spectrum was acquired in the negative ion mode with a high-resolution hybrid time-of-flight mass spectrometer. The ions were present in the form of [M + xNa(K) − (x + n)H]n−. The corresponding molecular weights and DP were then calculated using the monoisotopic peaks and charge states of each group of ions. Full article ">Figure 3
(A) A representative two-dimensional electrophoresis (2-DE) gel showing of total proteins from untreated and GOS-treated RAW264.7 cells. Each gel is representative of three independent replicates. Differentially regulated proteins (≥2.0-fold) are indicated by arrows and numbers and are listed in <a href="#marinedrugs-13-01798-t002" class="html-table">Table 2</a>; (B) Magnified image of an identified protein spot. Full article ">Figure 4
Western blot analysis of altered proteins in GOS-treated RAW264.7 cells. A representative result of three independent experiments is shown. Typical experiment conducted three times with similar results. β-tubulin was used as an internal control. Full article ">Figure 5
Effects of GOS on the morphology and actin organization of RAW264.7 cells. RAW264.7 cell morphology was observed by dark-field and confocal microscopy (×40). The cells were treated with or without 1 mg/mL GOS for 24 h. Representative dark-field images and analysis results show that GOS induced morphological changes in RAW264.7 cells, including an increase in the cell number (A,B), larger cell sizes (C,D), extended nucleus areas (E,F), and a greater number of dual-nuclei cells (G,H), compared with untreated cells (control). F-actin was stained with FITC-phalloidin. GOS-induced F-actin organization was examined using fluorescence images (I) and quantitative analysis (J). Scale bar, 20 µm. All images were analyzed with ImageJ software. ** p < 0.01 and *** p < 0.001 indicate significant differences between the control group and the GOS-treated group. Full article ">Figure 5 Cont.
Effects of GOS on the morphology and actin organization of RAW264.7 cells. RAW264.7 cell morphology was observed by dark-field and confocal microscopy (×40). The cells were treated with or without 1 mg/mL GOS for 24 h. Representative dark-field images and analysis results show that GOS induced morphological changes in RAW264.7 cells, including an increase in the cell number (A,B), larger cell sizes (C,D), extended nucleus areas (E,F), and a greater number of dual-nuclei cells (G,H), compared with untreated cells (control). F-actin was stained with FITC-phalloidin. GOS-induced F-actin organization was examined using fluorescence images (I) and quantitative analysis (J). Scale bar, 20 µm. All images were analyzed with ImageJ software. ** p < 0.01 and *** p < 0.001 indicate significant differences between the control group and the GOS-treated group. Full article ">Figure 6
Effects of GOS on the lipopolysaccharide (LPS)-activated morphological changes in RAW264.7 cells. The morphologies of RAW264.7 cells were visualized with a phase contrast microscope (×40). The cells were pretreated with 1 mg/mL GOS for 2 h before incubation with 1 μg/mL LPS for 24 h. (A) Control; (B) LPS-treated only; and (C) LPS-treated with GOS. Scale bar, 20 µm. Full article ">

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Open AccessArticle

Structural Analysis and Anti-Complement Activity of Polysaccharides from Kjellmaniella crsaaifolia

by Wenjing Zhang, Weihua Jin, Delin Sun, Luyu Zhao, Jing Wang, Delin Duan and Quanbin Zhang

Mar. Drugs 2015, 13(3), 1360-1374; https://doi.org/10.3390/md13031360 - 16 Mar 2015

Cited by 17 | Viewed by 6489

Abstract

Two polysaccharides, named KCA and KCW, were extracted from Kjellmaniella crassifolia using dilute hydrochloric acid and water, respectively. Composition analysis showed that these polysaccharides predominantly consisted of fucose, with galactose, mannose and glucuronic acid as minor components. After degradation and partial desulfation, electrospray [...] Read more.

Two polysaccharides, named KCA and KCW, were extracted from Kjellmaniella crassifolia using dilute hydrochloric acid and water, respectively. Composition analysis showed that these polysaccharides predominantly consisted of fucose, with galactose, mannose and glucuronic acid as minor components. After degradation and partial desulfation, electrospray ionization mass spectrometry (ESI-MS) was performed, which showed that the polysaccharides consisted of sulfated fucooligosaccharides, sulfated galactofucooligosaccharides and methyl glycosides of mono-sulfated/multi-sulfated fucooligosaccharides. The structures of the oligomeric fragments were further characterized by electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MS² and ESI-CID-MS³). Moreover, the activity of KCA and KCW against the hemolytic activity of both the classical and alternative complement pathways was determined. The activity of KCA was found to be similar to KCW, suggesting that the method of extraction did not influence the activity. In addition, the degraded polysaccharides (DKCA and DKCW) displayed lower activity levels than the crude polysaccharides (KCA and KCW), indicating that molecular weight had an effect on activity. Moreover, the desulfated fractions (ds-DKCA and ds-DKCW) showed less or no activity, which confirmed that sulfate was important for activity. In conclusion, polysaccharides from K. crassifolia may be good candidates for the treatment of diseases involving the complement pathway. Full article

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The IR spectra of polysaccharides. Full article ">Figure 2
Negative ion mode ESI-MS spectra of ds-DKCW (a) and ds-DKCA (b). Full article ">Figure 3
Negative ion mode ESI-CID-MS2 spectrum of the ion [MeFuc7SO3Na-Na]− at m/z 1133.415 (−1). Full article ">Figure 4
Negative ion mode ESI-CID-MS2 spectrum of the ion at m/z 421.129 (−2) (a) and negative ion mode ESI-CID-MS3 spectra of the ions at m/z 681.208(−1) (b) and 383.103 (−2) (c). Full article ">Figure 5
Negative ion mode ESI-CID-MS2 spectrum of the ion [MeFuc5(SO3Na)2-2Na]2− at m/z 460.120 (−2). Full article ">Figure 6
Negative ion mode ESI-MS2 spectrum of ion [Fuc6(SO3Na)2-2Na]2− at m/z 526.141 (−2). Full article ">Figure 7
Inhibition of the classical pathway-mediated hemolysis of EA (a and b) and alternative pathway-mediated hemolysis of ER (c and d) in 1:10-diluted NHS in the presence of increasing amounts of the polysaccharides. Heparin was used as the reference. The results are expressed as percent inhibition of hemolysis. Data are the means from 3 determinations ± S.E.M. Full article ">

914 KiB

Open AccessArticle

Acetylated Chitosan Oligosaccharides Act as Antagonists against Glutamate-Induced PC12 Cell Death via Bcl-2/Bax Signal Pathway

by Cui Hao, Lixia Gao, Yiran Zhang, Wei Wang, Guangli Yu, Huashi Guan, Lijuan Zhang and Chunxia Li

Mar. Drugs 2015, 13(3), 1267-1289; https://doi.org/10.3390/md13031267 - 12 Mar 2015

Cited by 40 | Viewed by 9007

Abstract

Chitosan oligosaccharides (COSs), depolymerized products of chitosan composed of β-(1→4) d-glucosamine units, have broad range of biological activities such as antitumour, antifungal, and antioxidant activities. In this study, peracetylated chitosan oligosaccharides (PACOs) and N-acetylated chitosan oligosaccharides (NACOs) were prepared from the COSs [...] Read more.

Chitosan oligosaccharides (COSs), depolymerized products of chitosan composed of β-(1→4) d-glucosamine units, have broad range of biological activities such as antitumour, antifungal, and antioxidant activities. In this study, peracetylated chitosan oligosaccharides (PACOs) and N-acetylated chitosan oligosaccharides (NACOs) were prepared from the COSs by chemcal modification. The structures of these monomers were identified using NMR and ESI-MS spectra. Their antagonist effects against glutamate-induced PC12 cell death were investigated. The results showed that pretreatment of PC12 cells with the PACOs markedly inhibited glutamate-induced cell death in a concentration-dependent manner. The PACOs were better glutamate antagonists compared to the COSs and the NACOs, suggesting the peracetylation is essential for the neuroprotective effects of chitosan oligosaccharides. In addition, the PACOs pretreatment significantly reduced lactate dehydrogenase release and reactive oxygen species production. It also attenuated the loss of mitochondrial membrane potential. Further studies indicated that the PACOs inhibited glutamate-induced cell death by preventing apoptosis through depressing the elevation of Bax/Bcl-2 ratio and caspase-3 activation. These results suggest that PACOs might be promising antagonists against glutamate-induced neural cell death. Full article

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1198 KiB

Open AccessArticle

Conformational Analysis of the Oligosaccharides Related to Side Chains of Holothurian Fucosylated Chondroitin Sulfates

by Alexey G. Gerbst, Andrey S. Dmitrenok, Nadezhda E. Ustyuzhanina and Nikolay E. Nifantiev

Mar. Drugs 2015, 13(2), 936-947; https://doi.org/10.3390/md13020936 - 12 Feb 2015

Cited by 7 | Viewed by 5992

Abstract

Anionic polysaccharides fucosylated chondroitin sulfates (FCS) from holothurian species were shown to affect various biological processes, such as metastasis, angiogenesis, clot formation, thrombosis, inflammation, and some others. To understand the mechanism of FCSs action, knowledge about their spatial arrangement is required. We have [...] Read more.

Anionic polysaccharides fucosylated chondroitin sulfates (FCS) from holothurian species were shown to affect various biological processes, such as metastasis, angiogenesis, clot formation, thrombosis, inflammation, and some others. To understand the mechanism of FCSs action, knowledge about their spatial arrangement is required. We have started the systematic synthesis, conformational analysis, and study of biological activity of the oligosaccharides related to various fragments of these types of natural polysaccharides. In this communication, five molecules representing distinct structural fragments of chondroitin sulfate have been studied by means of molecular modeling and NMR. These are three disaccharides and two trisaccharides containing fucose and glucuronic acid residues with one sulfate group per each fucose residue or without it. Long-range C–H coupling constants were used for the verification of the theoretical models. The presence of two conformers for both linkage types was revealed. For the Fuc–GlA linkage, the dominant conformer was the same as described previously in a literature as the molecular dynamics (MD) average in a dodechasaccharide FCS fragment representing the backbone chain of the polysaccharide including GalNAc residues. This shows that the studied oligosaccharides, in addition to larger ones, may be considered as reliable models for Quantitative Structure-Activity Relationship (QSAR) studies to reveal pharmacophore fragments of FCS. Full article

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2014

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708 KiB

Open AccessArticle

Preliminary Characterization, Antioxidant Properties and Production of Chrysolaminarin from Marine Diatom Odontella aurita

by Song Xia, Baoyan Gao, Aifen Li, Jihai Xiong, Ziqiang Ao and Chengwu Zhang

Mar. Drugs 2014, 12(9), 4883-4897; https://doi.org/10.3390/md12094883 - 23 Sep 2014

Cited by 93 | Viewed by 9681

Abstract

A new chrysolaminarin, named CL2, with a molecular mass of 7.75 kDa, was purified from the marine diatom, Odontella aurita, using DEAE-52 cellulose anion-exchange chromatography and Sephadex G-200 gel-filtration chromatography. The monosaccharide and structural analysis revealed that CL2 was a glucan mainly [...] Read more.

A new chrysolaminarin, named CL2, with a molecular mass of 7.75 kDa, was purified from the marine diatom, Odontella aurita, using DEAE-52 cellulose anion-exchange chromatography and Sephadex G-200 gel-filtration chromatography. The monosaccharide and structural analysis revealed that CL2 was a glucan mainly composed of glucose, which was linked by the β-d-(1→3) (main chain) and β-d-(1→6) (side chain) glycosidic bond, demonstrated by infrared spectroscopy (IR) and nuclear magnetic resonance (NMR). The antioxidant activity tests revealed that the CL2 presented stronger hydroxyl radical scavenging activity with increasing concentrations, but less was effective on reducing power analysis and scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The influences of nitrogen concentration and light intensity on chrysolaminarin production of O. aurita were further investigated in a glass column photobioreactor, and a record high chrysolaminarin productivity of 306 mg L⁻¹ day⁻¹ was achieved. In conclusion, the chrysolaminarin CL2 from O. aurita may be explored as a natural antioxidant agent for application in aquaculture, food and pharmaceutical areas. Full article

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DEAE-cellulose column elution profile of crude polysaccharide from O. aurita. Full article ">Figure 2
Sephadex G-200 gel-filtration chromatogram of the fraction CL1 (chrysolaminarin 1) obtained from DEAE-cellulose column elution. Full article ">Figure 3
The FTIR spectra of CL2 from O. aurita. Full article ">Figure 4
(a) 1H-NMR and (b) 13C-NMR spectrum of CL2 from O. aurita (NA: not assigned). Full article ">Figure 5
Antioxidant assays for the chrysolaminarin CL2 from O. aurita. (a) Reducing power; (b) scavenging of DPPH radicals; (c) scavenging of hydroxyl radicals. Values are the means ± SD (n = 3). When error bars cannot be seen, the error is less than the size of the symbol. Full article ">Figure 6
The biomass (a,b) and chrysolaminarin content (c,d) of O. aurita cultivated in the column photobioreactor under 100 (a,c) and 300 (b,d) μmol photons m−2 s−1 with a replete (18 mM) and deficient (6 mM) nitrate supply. Values are the means ± SD (n = 3). When error bars cannot be seen, the error is less than the size of the symbol. Full article ">Figure 7
Isolation and purification procedure of chrysolaminarin from O. aurita. Full article ">

2013

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964 KiB

Open AccessArticle

Isolation and Structural Characterization of a Novel Antioxidant Mannoglucan from a Marine Bubble Snail, Bullacta exarata (Philippi)

by Donghong Liu, Ningbo Liao, Xingqian Ye, Yaqin Hu, Dan Wu, Xin Guo, Jianjun Zhong, Jianyong Wu and Shiguo Chen

Mar. Drugs 2013, 11(11), 4464-4477; https://doi.org/10.3390/md11114464 - 11 Nov 2013

Cited by 17 | Viewed by 8223

Abstract

Bullacta exarata is one of the most economically important aquatic species in China, noted for not only its delicious taste and nutritional value, but also for its pharmacological activities. In order to explore its potential in medical applications, a mannoglucan designated as BEPS-IB [...] Read more.

Bullacta exarata is one of the most economically important aquatic species in China, noted for not only its delicious taste and nutritional value, but also for its pharmacological activities. In order to explore its potential in medical applications, a mannoglucan designated as BEPS-IB was isolated and purified from the foot muscle of B. exarata after papain digestion. Chemical composition analysis indicated BEPS-IB contained mainly d-glucose and d-mannose in a molar ratio of 1:0.52, with an average molecular weight of about 94 kDa. The linkage information was determined by methylation analysis, and the anomeric configuration and chain linkage were confirmed by IR and 2D NMR. The results indicated BEPS-IB was composed of Glcp₆Manp heptasaccharide repeating unit in the backbone, with occasional branch chains of mannose residues (14%) occurring in the backbone mannose. Further antioxidant assay indicated BEPS-IB exhibited positive antioxidant activity in scavenging superoxide radicals and reducing power. This is the first report on the structure and bioactivity of the mannoglucan from the B. exarata. Full article

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Isolation of the polysaccharides present in the aqueous extract of B. exarata. The crude extract was fractionated by ion-exchange chromatography on a DEAE ion-exchange column (a) and the collected fraction was further purified by gel filtration chromatography on a Sephacryl S-300 HR column (b). Solid bars indicate the fractions collected. The molecular weight of polysaccharide fraction BEPS-IB (Mw = 94 kDa) was determined by HPLC on a TSK-Gel G4000 PWXL column, eluted with 0.2 mol/L NaCl at 0.5 mL/min (c). Range of molecular weight in kDa: I = 500; II = 66.9; III = 40. Full article ">Figure 2
Infrared spectra of polysaccharide (BEPS-IB) from B. exarata. Full article ">Figure 3
1H NMR (a) and 13C NMR (b) spectrum (600 MHz, D2O, 60 °C) of BEPS-IB isolated from B. exarata. Full article ">Figure 4
HMQC spectrum of BEPS-IB isolated from B. exarata. Full article ">Figure 5
Proposed structural features of the BEPS-IB isolated from B. exarata. Full article ">Figure 6
Antioxidant activity of the BEPS-IB. (a) Scavenging effects of BEPS-IB on superoxide radical (O2•); (b) Reducing power. Values are means ± SD (n = 3). Significant differences from the control were evaluated using Student’s t-test: * p < 0.05. Reducing power was expressed as a percentage of the activity shown by vitamin C. Full article ">

768 KiB

Open AccessReview

Chondroitin Sulfate, Hyaluronic Acid and Chitin/Chitosan Production Using Marine Waste Sources: Characteristics, Applications and Eco-Friendly Processes: A Review

by José Antonio Vázquez, Isabel Rodríguez-Amado, María Ignacia Montemayor, Javier Fraguas, María Del Pilar González and Miguel Anxo Murado

Mar. Drugs 2013, 11(3), 747-774; https://doi.org/10.3390/md11030747 - 11 Mar 2013

Cited by 210 | Viewed by 25412

Abstract

In the last decade, an increasing number of glycosaminoglycans (GAGs), chitin and chitosan applications have been reported. Their commercial demands have been extended to different markets, such as cosmetics, medicine, biotechnology, food and textiles. Marine wastes from fisheries and aquaculture are susceptible sources [...] Read more.

In the last decade, an increasing number of glycosaminoglycans (GAGs), chitin and chitosan applications have been reported. Their commercial demands have been extended to different markets, such as cosmetics, medicine, biotechnology, food and textiles. Marine wastes from fisheries and aquaculture are susceptible sources for polymers but optimized processes for their recovery and production must be developed to satisfy such necessities. In the present work, we have reviewed different alternatives reported in the literature to produce and purify chondroitin sulfate (CS), hyaluronic acid (HA) and chitin/chitosan (CH/CHs) with the aim of proposing environmentally friendly processes by combination of various microbial, chemical, enzymatic and membranes strategies and technologies. Full article

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2012

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631 KiB

Open AccessArticle

Effect of Fucoidan Extracted from Mozuku on Experimental Cartilaginous Tissue Injury

by Tomohiro Osaki, Koudai Kitahara, Yoshiharu Okamoto, Tomohiro Imagawa, Takeshi Tsuka, Yasunari Miki, Hitoshi Kawamoto, Hiroyuki Saimoto and Saburo Minami

Mar. Drugs 2012, 10(11), 2560-2570; https://doi.org/10.3390/md10112560 - 13 Nov 2012

Cited by 9 | Viewed by 7607

Abstract

We investigated the effect of fucoidan, a sulfated polysaccharide, on acceleration of healing of experimental cartilage injury in a rabbit model. An injured cartilage model was surgically created by introduction of three holes, one in the articular cartilage of the medial trochlea and [...] Read more.

We investigated the effect of fucoidan, a sulfated polysaccharide, on acceleration of healing of experimental cartilage injury in a rabbit model. An injured cartilage model was surgically created by introduction of three holes, one in the articular cartilage of the medial trochlea and two in the trochlear sulcus of the distal femur. Rabbits in three experimental groups (F groups) were orally administered fucoidan of seven different molecular weights (8, 50, 146, 239, 330, 400, or 1000 kD) for 3 weeks by screening. Control (C group) rabbits were provided water ad libitum. After the experimental period, macroscopic examination showed that the degree of filling in the fucoidan group was higher than that in the C group. Histologically, the holes were filled by collagen fiber and fibroblasts in the C group, and by chondroblasts and fibroblasts in the F groups. Image analysis of Alcian blue- and safranin O-stained F-group specimens showed increased production of glycosaminoglycans (GAGs) and proteoglycans (PGs), respectively. Some injured holes were well repaired both macroscopically and microscopically and were filled with cartilage tissues; cartilage matrices such as PGs and GAGs were produced in groups F 50, F 146, and F 239. Thus, fucoidan administration enhanced morphologically healing of cartilage injury. Full article

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Figure 1
Average defect restoration scores. Data are expressed as the average ± standard deviation. * p < 0.05. Full article ">Figure 2
Light microscopy of tissues from each group (HE stain; 40×). (A) C group; (B) F 8 group; (C) F 50 group; (D) F 146 group; (E) F 239 group; (F) F 330 group; (G) F 400 group; (H) F 1000 group. (a) cartilage layer; (b) superficial layer of cancellous bone; (c) deeper layer of cancellous bone. * joint cavity. Full article ">Figure 3
Light microscopy of tissues from each group (Alcian blue stain; ×40). (A) C group; (B) F 8 group; (C) F 50 group; (D) F 146 group; (E) F 239 group; (F) F 330 group; (G) F 400 group; (H) F 1000 group. Full article ">Figure 4
Light microscopy of tissues from each group (safranin O stain; 40×). (A) C group; (B) F 8 group; (C) F 50 group; (D) F 146 group; (E) F 239 group, (F) F 330 group; (G) F 400 group; (H) F 1000 group. Full article ">Figure 5
Image analysis of Alcian blue-stained specimens. Data are expressed as the average ± standard deviation. *p < 0.05. Full article ">Figure 6
Image analysis of safranin O-stained specimens. The data are expressed as the average ± standard deviation. * p < 0.05. Full article ">

1964 KiB

Open AccessArticle

Structural Analysis of a Heteropolysaccharide from Saccharina japonica by Electrospray Mass Spectrometry in Tandem with Collision-Induced Dissociation Tandem Mass Spectrometry (ESI-CID-MS/MS)

by Weihua Jin, Jing Wang, Sumei Ren, Ni Song and Quanbin Zhang

Mar. Drugs 2012, 10(10), 2138-2152; https://doi.org/10.3390/md10102138 - 25 Sep 2012

Cited by 49 | Viewed by 9448

Abstract

A fucoidan extracted from Saccharina japonica was fractionated by anion exchange chromatography. The most complex fraction F0.5 was degraded by dilute sulphuric acid and then separated by use of an activated carbon column. Fraction Y1 was fractionated by anion exchange and gel filtration [...] Read more.

A fucoidan extracted from Saccharina japonica was fractionated by anion exchange chromatography. The most complex fraction F0.5 was degraded by dilute sulphuric acid and then separated by use of an activated carbon column. Fraction Y1 was fractionated by anion exchange and gel filtration chromatography while Fraction Y2 was fractionated by gel filtration chromatography. The fractions were determined by ESI-MS and analyzed by ESI-CID-MS/MS. It was concluded that F0.5 had a backbone of alternating 4-linked GlcA and 2-linked Man with the first Man residue from the nonreducing end accidentally sulfated at C6. In addition, F0.5 had a 3-linked glucuronan, in accordance with a previous report by NMR. Some other structural characteristics included GlcA 1→3 Man 1→4 GlcA, Man 1→3 GlcA 1→4 GlcA, Fuc 1→4 GlcA and Fuc 1→3 Fuc. Finally, it was shown that fucose was sulfated at C2 or C4 while galactose was sulfated at C2, C4 or C6. Full article

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Figure 1
Gel filtration chromatography of Y2 oligosaccharide on a Bio-Gel P-4 Gel column. Full article ">Figure 2
Negative-ion mode electrospray mass spectrometry (ESI-MS) spectra of YF (a), YD-1 (b), YD-2 (c) and YT (d). Full article ">Figure 3
Negative-ion mode ESI-MS spectra and HPLC spectra of G1 (d,D-1), G2 (c,C-1), G3 (b,B-1) and G4 (a,A-1). Full article ">Figure 4
Negative-ion mode electrospray mass spectrometry in tandem with collision-induced dissociation tandem mass spectrometry (ESI-CID-MS/MS) spectrum of the ion at m/z 309.112. Full article ">Figure 5
Negative-ion mode ESI-CID-MS/MS spectrum of the ion at m/z 339.230. Full article ">Figure 6
Negative-ion mode ESI-CID-MS/MS spectra of the ions at m/z 545.096 (a) and 531.117 (b). Full article ">Figure 7
Negative-ion mode ESI-CID-MS/MS spectra of the ions at m/z 1031.250 (a) and 555.100 (−2) (b). Full article ">

2011

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852 KiB

Open AccessReview

Marine Polysaccharides in Microencapsulation and Application to Aquaculture: “From Sea to Sea”

by Massimiliano Borgogna, Barbara Bellich and Attilio Cesàro

Mar. Drugs 2011, 9(12), 2572-2604; https://doi.org/10.3390/md9122572 - 8 Dec 2011

Cited by 38 | Viewed by 12179

Abstract

This review’s main objective is to discuss some physico-chemical features of polysaccharides as intrinsic determinants for the supramolecular structures that can efficiently provide encapsulation of drugs and other biological entities. Thus, the general characteristics of some basic polysaccharides are outlined in terms of [...] Read more.

This review’s main objective is to discuss some physico-chemical features of polysaccharides as intrinsic determinants for the supramolecular structures that can efficiently provide encapsulation of drugs and other biological entities. Thus, the general characteristics of some basic polysaccharides are outlined in terms of their conformational, dynamic and thermodynamic properties. The analysis of some polysaccharide gelling properties is also provided, including the peculiarity of the charged polysaccharides. Then, the way the basic physical chemistry of polymer self-assembly is made in practice through the laboratory methods is highlighted. A description of the several literature procedures used to influence molecular interactions into the macroscopic goal of the encapsulation is given with an attempt at classification. Finally, a practical case study of specific interest, the use of marine polysaccharide matrices for encapsulation of vaccines in aquaculture, is reported. Full article

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Figure 1
General mechanism (nucleation and growth) of gel formation as macroscopically measured by viscoelastic, optical and chiroptical properties. The insets show sketch of the polymer solution microstructure at the various stages. Full article ">Figure 2
Schematic representation of the Gibbs free-energy curve vs. temperature for the liquid phase (as a function of composition, blue lines); and for the crystalline phase as a function of decreasing crystal size (red lines). The practical effect is a decrease in the measured melting temperature. Full article ">Figure 3
Structural representation of four disaccharides from glucose: (a) maltose (α-(1-4)-linked); (b) nigerose (α-(1-3)-linked); (c) cellobiose (β-(1-4)-linked); (d) laminarabiose (β-(1-3)-linked). The related polysaccharide structures of amylose (A), nigeran (B), cellulose (C) and laminaran (D) are shown in the ordered helical conformations as measured by X-ray fiber diffraction studies (left) and as snapshots of random chains modeled by Monte Carlo calculation (right). Full article ">Figure 4
Correlation between structural conformational data obtained by scattering experiments (top) and structural data obtained by molecular thermodynamic theories (bottom). The example refers to the chain mass-per-unit length (from light scattering) and to the average distance between charged groups (from potentiometry or calorimetry). Full article ">Figure 5
Schematic representation of the methods described for gel particle technology. Full article ">Figure 6
Graphical classification of the encapsulation procedures and techniques in polysaccharide hydrogels. Full article ">Figure 7
(a) Comparison of lysozyme release from alginate beads in phosphate buffer (●) and in Tris/NaCl (■) at pH = 7.4; (b) Comparison of lysozyme release in Tris/NaCl from alginate beads (■) and from alginate/chitosan beads (▲); (c) Experimental integral heat of water evaporation from alginate beads (curve a); and from alginate/chitosan beads (curve b). Polymer samples: alginate (FG = 0.4; Mv = 86 kDa); chitosan (Mv = 492 kDa; DA = 11%). Other experimental details in refs [<a href="#B182-marinedrugs-09-02572" class="html-bibr">182</a>,<a href="#B183-marinedrugs-09-02572" class="html-bibr">183</a>]. Full article ">

499 KiB

Open AccessArticle

Sulfated-Polysaccharide Fraction from Red Algae Gracilaria caudata Protects Mice Gut Against Ethanol-Induced Damage

by Renan Oliveira Silva, Geice Maria Pereira dos Santos, Lucas Antonio Duarte Nicolau, Larisse Tavares Lucetti, Ana Paula Macedo Santana, Luciano de Souza Chaves, Francisco Clark Nogueira Barros, Ana Lúcia Ponte Freitas, Marcellus Henrique Loiola Ponte Souza and Jand-Venes Rolim Medeiros

Mar. Drugs 2011, 9(11), 2188-2200; https://doi.org/10.3390/md9112188 - 2 Nov 2011

Cited by 48 | Viewed by 9773

Abstract

The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and [...] Read more.

The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg⁻¹, p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g⁻¹, p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg⁻¹, i.p.), dl-propargylglycine (PAG, 50 mg·kg⁻¹, p.o.) or glibenclamide (5 mg·kg⁻¹, i.p.). After 1 h, PLS (30 mg·kg⁻¹, p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25g⁻¹, p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/K_ATP pathway. Full article

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Graphical abstract

Graphical abstract
Full article ">
The effect of PLS on ethanol-induced gastric damage. Mice were treated by gavage with either saline or PLS (3, 10, 30 and 90·mg·kg−1). Thirty minutes later, mice in experimental groups were administered 50% ethanol (0.5 mL/25 g−1); the negative control group was administered saline. The total area of macroscopic gastric lesions was determined after 1 h. The results are expressed as mean ± SEM of a minimum of 5 animals per group. # p < 0.05 vs. saline group; * p < 0.05 vs. ethanol group; ANOVA and Newman-Keuls test. Full article ">
Photomicrographs of gastric mucosa (Magnification, 100×): (A) saline control; (B) animals treated with 50% ethanol, showing disruption of the superficial region of the gastric gland with epithelial cell loss and intense hemorrhage; (C) animals treated with 50% ethanol + polysaccharide (30 mg·kg−1), showing preservation of the gastric mucosa. Quantitative results from these assessments are shown in <a href="#t1-marinedrugs-09-02188" class="html-table">Table 1</a>. Full article ">
The effect of PLS on glutathione (GSH) levels in the gastric mucosa of mice treated with ethanol. Mice were treated by gavage with saline or PLS (30 mg·kg−1). Thirty minutes later, 50% ethanol (0.5 mL 25 g−1) was administered to the experimental groups, while the control group was administered saline. Ethanol administration promoted a reduction in the GSH gastric levels. This effect was partially reverted when the animals were treated with PLS. The results are expressed as mean ± SEM of 5 animals per group. # p < 0.05 vs. saline group; * p < 0.05 vs. ethanol group; ANOVA and Newman-Keuls test. Full article ">
The effect of PLS on malondialdehyde (MDA) concentration in the gastric mucosa of mice treated with ethanol. Mice were treated by gavage with PLS (30 mg·kg−1). Thirty minutes later, mice in the experimental group were administered 50% ethanol (0.5 mL 25 g−1), and the control group was administered saline. The ethanol evidently promoted an increase in MDA gastric levels. When the animals were pre-treated with PLS, this effect was reverted. The results are expressed as the Means ± SEM of 5 animals per group. # p < 0.05 vs. saline group; * p < 0.05 vs. ethanol group; ANOVA and Newman-Keuls test. Full article ">
The effect of l-NAME, PAG, and glibenclamide on PLS-mediated protection against macroscopically visible ethanol-induced gastric damage. Mice were initially treated with l-NAME (10 mg·kg−1, i.p.), dl-propargylglycine (PAG, 50 mg·kg−1, p.o.), or glibenclamide (5 mg·kg−1, i.p.). After 1 h, PLS (30 mg·kg−1, p.o.) was administered. Thirty minutes later, 50% ethanol was administered to the experimental groups, and the control group was administered saline. The total area of the macroscopic gastric lesions was determined after 1 h. The results are expressed as mean ± SEM of a minimum of 5 animals per group. * p < 0.05 vs. ethanol group; # p < 0.05 vs. PLS + ethanol group; ANOVA and Newman-Keuls test. Full article ">

1943 KiB

Open AccessReview

The Structural Diversity of Carbohydrate Antigens of Selected Gram-Negative Marine Bacteria

by Evgeny L. Nazarenko, Russell J. Crawford and Elena P. Ivanova

Mar. Drugs 2011, 9(10), 1914-1954; https://doi.org/10.3390/md9101914 - 14 Oct 2011

Cited by 39 | Viewed by 10677

Abstract

Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active [...] Read more.

Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents, and as a result, they have been a topic of research interest for many years. Among these biologically active molecules, the carbohydrate antigens, lipopolysaccharides (LPSs, O-antigens) found in cell walls of Gram-negative marine bacteria, show great potential as candidates in the development of drugs to prevent septic shock due to their low virulence. The structural diversity of LPSs is thought to be a reflection of the ability for these bacteria to adapt to an array of habitats, protecting the cell from being compromised by exposure to harsh environmental stress factors. Over the last few years, the variety of structures of core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been discovered. In this review, we discuss the most recently encountered structures that have been identified from bacteria belonging to the genera Aeromonas, Alteromonas, Idiomarina, Microbulbifer, Pseudoalteromonas, Plesiomonas and Shewanella of the Gammaproteobacteria phylum; Sulfitobacter and Loktanella of the Alphaproteobactera phylum and to the genera Arenibacter, Cellulophaga, Chryseobacterium, Flavobacterium, Flexibacter of the Cytophaga-Flavobacterium-Bacteroides phylum. Particular attention is paid to the particular chemical features of the LPSs, such as the monosaccharide type, non-sugar substituents and phosphate groups, together with some of the typifying traits of LPSs obtained from marine bacteria. A possible correlation is then made between such features and the environmental adaptations undertaken by marine bacteria. Full article

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266 KiB

Open AccessReview

Therapies from Fucoidan; Multifunctional Marine Polymers

by Janet Helen Fitton

Mar. Drugs 2011, 9(10), 1731-1760; https://doi.org/10.3390/md9101731 - 30 Sep 2011

Cited by 296 | Viewed by 20777

Abstract

Published research on fucoidans increased three fold between 2000 and 2010. These algal derived marine carbohydrate polymers present numerous valuable bioactivities. This review discusses the role for fucoidan in the control of acute and chronic inflammation via selectin blockade, enzyme inhibition and inhibiting [...] Read more.

Published research on fucoidans increased three fold between 2000 and 2010. These algal derived marine carbohydrate polymers present numerous valuable bioactivities. This review discusses the role for fucoidan in the control of acute and chronic inflammation via selectin blockade, enzyme inhibition and inhibiting the complement cascade. The recent data on toxicology and uptake of fucoidan is detailed together with a discussion on the comparative activities of fractions of fucoidan from different sources. Recent in vivo, in vitro and clinical research related to diverse clinical needs is discussed. Targets include osteoarthritis, kidney and liver disease, neglected infectious diseases, hemopoietic stem cell modulation, protection from radiation damage and treatments for snake envenomation. In recent years, the production of well characterized reproducible fucoidan fractions on a commercial scale has become possible making therapies from fucoidan a realizable goal. Full article

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Open AccessReview

Marine Polysaccharides: A Source of Bioactive Molecules for Cell Therapy and Tissue Engineering

by Karim Senni, Jessica Pereira, Farida Gueniche, Christine Delbarre-Ladrat, Corinne Sinquin, Jacqueline Ratiskol, Gaston Godeau, Anne-Marie Fischer, Dominique Helley and Sylvia Colliec-Jouault

Mar. Drugs 2011, 9(9), 1664-1681; https://doi.org/10.3390/md9091664 - 23 Sep 2011

Cited by 235 | Viewed by 17068

Abstract

The therapeutic potential of natural bioactive compounds such as polysaccharides, especially glycosaminoglycans, is now well documented, and this activity combined with natural biodiversity will allow the development of a new generation of therapeutics. Advances in our understanding of the biosynthesis, structure and function [...] Read more.

The therapeutic potential of natural bioactive compounds such as polysaccharides, especially glycosaminoglycans, is now well documented, and this activity combined with natural biodiversity will allow the development of a new generation of therapeutics. Advances in our understanding of the biosynthesis, structure and function of complex glycans from mammalian origin have shown the crucial role of this class of molecules to modulate disease processes and the importance of a deeper knowledge of structure-activity relationships. Marine environment offers a tremendous biodiversity and original polysaccharides have been discovered presenting a great chemical diversity that is largely species specific. The study of the biological properties of the polysaccharides from marine eukaryotes and marine prokaryotes revealed that the polysaccharides from the marine environment could provide a valid alternative to traditional polysaccharides such as glycosaminoglycans. Marine polysaccharides present a real potential for natural product drug discovery and for the delivery of new marine derived products for therapeutic applications. Full article

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Cell surface GAGs and cell behavior. (a) GAGs and cell adhesion; (b) GAGs and growth factor promotion. Full article ">
Cell surface GAGs and cell behavior. (a) GAGs and cell adhesion; (b) GAGs and growth factor promotion. Full article ">
Structure of sulfated oligofucoidan constitutive of algal fucoidan from Ascophyllum nodosum [<a href="#b32-marinedrugs-09-01664" class="html-bibr">32</a>]. Full article ">
Angiographies of hind limbs from rabbits, 3 days after apoptosis induction. (a) Rabbit receiving LMWF; (b) Rabbit receiving placebo. Full article ">
Repeating unit of the marine bacterial polysaccharide (HE800 EPS) produced by Vibrio diabolicus [<a href="#b68-marinedrugs-09-01664" class="html-bibr">68</a>]. Full article ">
Effect of the DRS HE800 derivative on vascular tube formation on Matrigel from endothelial progenitor cells (EPCs). Photographs show vascular tube formation by EPCs previously treated (a) with 5% of fetal calf serum (control); (b) with proangiogenic factor VEGF (40 ng/mL); and (c) with proangiogenic factor VEGF (40 ng/mL) and DRS HE800 derivative (10 μg/mL). Full article ">
Repeating unit of marine bacterial polysaccharide (GY785 EPS) produced by Alteromonas infernus [<a href="#b74-marinedrugs-09-01664" class="html-bibr">74</a>,<a href="#b75-marinedrugs-09-01664" class="html-bibr">75</a>]. Full article ">

644 KiB

Open AccessReview

Biomedical Exploitation of Chitin and Chitosan via Mechano-Chemical Disassembly, Electrospinning, Dissolution in Imidazolium Ionic Liquids, and Supercritical Drying

by Riccardo A. A. Muzzarelli

Mar. Drugs 2011, 9(9), 1510-1533; https://doi.org/10.3390/md9091510 - 9 Sep 2011

Cited by 179 | Viewed by 15235

Abstract

Recently developed technology permits to optimize simultaneously surface area, porosity, density, rigidity and surface morphology of chitin-derived materials of biomedical interest. Safe and ecofriendly disassembly of chitin has superseded the dangerous acid hydrolysis and provides higher yields and scaling-up possibilities: the chitosan nanofibrils [...] Read more.

Recently developed technology permits to optimize simultaneously surface area, porosity, density, rigidity and surface morphology of chitin-derived materials of biomedical interest. Safe and ecofriendly disassembly of chitin has superseded the dangerous acid hydrolysis and provides higher yields and scaling-up possibilities: the chitosan nanofibrils are finding applications in reinforced bone scaffolds and composite dressings for dermal wounds. Electrospun chitosan nanofibers, in the form of biocompatible thin mats and non-wovens, are being actively studied: composites of gelatin + chitosan + polyurethane have been proposed for cardiac valves and for nerve conduits; fibers are also manufactured from electrospun particles that self-assemble during subsequent freeze-drying. Ionic liquids (salts of alkylated imidazolium) are suitable as non-aqueous solvents that permit desirable reactions to occur for drug delivery purposes. Gel drying with supercritical CO₂ leads to structures most similar to the extracellular matrix, even when the chitosan is crosslinked, or in combination with metal oxides of interest in orthopedics. Full article

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558 KiB

Open AccessArticle

Chitosan Nanoparticles Act as an Adjuvant to Promote both Th1 and Th2 Immune Responses Induced by Ovalbumin in Mice

by Zheng-Shun Wen, Ying-Lei Xu, Xiao-Ting Zou and Zi-Rong Xu

Mar. Drugs 2011, 9(6), 1038-1055; https://doi.org/10.3390/md9061038 - 14 Jun 2011

Cited by 176 | Viewed by 14105

Abstract

The study was conducted to investigate the promoted immune response to ovalbumin in mice by chitosan nanoparticles (CNP) and its toxicity. CNP did not cause any mortality or side effects when mice were administered subcutaneously twice with a dose of 1.5 mg at [...] Read more.

The study was conducted to investigate the promoted immune response to ovalbumin in mice by chitosan nanoparticles (CNP) and its toxicity. CNP did not cause any mortality or side effects when mice were administered subcutaneously twice with a dose of 1.5 mg at 7-day intervals. Institute of Cancer Research (ICR) mice were immunized subcutaneously with 25 µg ovalbumin (OVA) alone or with 25 µg OVA dissolved in saline containing Quil A (10 µg), chitosan (CS) (50 µg) or CNP (12.5, 50 or 200 µg) on days 1 and 15. Two weeks after the secondary immunization, serum OVA-specific antibody titers, splenocyte proliferation, natural killer (NK) cell activity, and production and mRNA expression of cytokines from splenocytes were measured. The serum OVA-specific IgG, IgG1, IgG2a, and IgG2b antibody titers and Con A-, LPS-, and OVA-induced splenocyte proliferation were significantly enhanced by CNP (P < 0.05) as compared with OVA and CS groups. CNP also significantly promoted the production of Th1 (IL-2 and IFN-γ) and Th2 (IL-10) cytokines and up-regulated the mRNA expression of IL-2, IFN-γ and IL-10 cytokines in splenocytes from the immunized mice compared with OVA and CS groups. Besides, CNP remarkably increased the killing activities of NK cells activity (P < 0.05). The results suggested that CNP had a strong potential to increase both cellular and humoral immune responses and elicited a balanced Th1/Th2 response, and that CNP may be a safe and efficacious adjuvant candidate suitable for a wide spectrum of prophylactic and therapeutic vaccines. Full article

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Morphology of chitosan nanoparticles (CNP). (A, B) atomic force micrographs (AFMs) of CNP; (C) the size distribution by intendity of CNP, the size of CNP ranges from 63.16 to 101.70 nm, and the mean of size is about 83.66 nm; (D) Zeta potential distribution of CNP, CNP exhibit a zeta potential range from 20.04 to 51.13 mV and have a mean charge with 35.43 mV. Full article ">
Effect of CNP on OVA-specific IgG, IgG1, IgG2a and IgG2b antibody titers in OVA-immunized mice. Mice (n = 6/group) were subcutaneously injected with OVA (25 μg) alone or with OVA 25 (μg) dissolved in saline containing CNP (12.5, 50 or 200 μg), CS (50 μg) or QuilA (10 μg) on days 1 and 15. Sera were collected 2 weeks after the secondary immunizations for analysis these OVA-specific antibodies using indirect ELISA. Bar with different letters are statistically different (P < 0.05). Abbreviations: QuilA: mixture of triterpene saponins from the bark of Quillaja saponaria Molina. Full article ">
Effect of CNP on NK cell activity in mice immunized with OVA. Mice (n = 6/group) were subcutaneously injected with OVA (25 μg) alone or with OVA 25 μg dissolved in saline containing CNP (12.5, 50 or 200 μg), CS (50 μg) or QuilA (10 μg) on days 1 and 15. Bars with different letters are statistically different (P < 0.05). Full article ">
Effect of CNP on mitogen- and OVA-stimulated splenocyte proliferation in the mice immunized with OVA. Bars with different letters are statistically different (P < 0.05). Full article ">
Effect of CNP on mitogen- and OVA-stimulated splenocyte proliferation in the mice immunized with OVA. Bars with different letters are statistically different (P < 0.05). Full article ">
Effects of CNP on cytokine production in splenocytes from the OVA-immunized mice. Splenocytes were prepared and cultured with Con A for 48 h. The levels of IL-2, IFN-γ and IL-10 in the culture supernatants were determined by ELISA as described in the text. Values are expressed as means ± S.D. of six animals. Bars with different letters are statistically different (P < 0.05). Full article ">
Eeffect of CNP on the mRNA expression of cytokines and GAPDH in splenocytes from the OVA-immunized mice. Lane M, DNA marker; lane 1, OVA; lane 2, QuilA; lane 3, OVA-CNP (12.5 μg); lane 4, OVA-CNP (50 μg); lane 5, OVA-CNP (200 μg); lane 6, OVA-CS (50 μg). Full article ">

2010

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1311 KiB

Open AccessArticle

Nature and Lability of Northern Adriatic Macroaggregates

by Jadran Faganeli, Bojana Mohar, Romina Kofol, Vesna Pavlica, Tjaša Marinšek, Ajda Rozman, Nives Kovač and Angela Šurca Vuk

Mar. Drugs 2010, 8(9), 2480-2492; https://doi.org/10.3390/md8092480 - 6 Sep 2010

Cited by 8 | Viewed by 9118

Abstract

The key organic constituents of marine macroaggregates (macrogels) of prevalently phytoplankton origin, periodically occurring in the northern Adriatic Sea, are proteins, lipids and especially polysaccharides. In this article, the reactivity of various macroaggregate fractions in relation to their composition in order to decode [...] Read more.

The key organic constituents of marine macroaggregates (macrogels) of prevalently phytoplankton origin, periodically occurring in the northern Adriatic Sea, are proteins, lipids and especially polysaccharides. In this article, the reactivity of various macroaggregate fractions in relation to their composition in order to decode the potentially »bioavailable« fractions is summarized and discussed. The enzymatic hydrolysis of the macroaggregate matrix, using α-amylase, β-glucosidase, protease, proteinase and lipase, revealed the simultaneous degradation of polysaccharides and proteins, while lipids seem largely preserved. In the fresh surface macroaggregate samples, a pronounced degradation of the α-glycosidic bond compared to β-linkages. Degradation of the colloidal fraction proceeded faster in the higher molecular weight (MW) fractions. N-containing polysaccharides can be important constituents of the higher MW fraction while the lower MW constituents can mostly be composed of poly- and oligosaccharides. Since the polysaccharide component in the higher MW fraction is more degradable compared to N‑containing polysaccharides, the higher MW fraction represents a possible path of organic nitrogen preservation. Enzymatic hydrolysis, using α-amylase and β-glucosidase, revealed the presence of α- and β-glycosidic linkages in all fractions with similar decomposition kinetics. Our results indicate that different fractions of macroaggregates are subjected to compositional selective reactivity with important implications for macroaggregate persistence in the seawater column and deposition. Full article

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FT-IR spectra of (A) macroaggregate matrix, surface sample (black bold line) and water column sample (black dotted line); and (B) macroaggregate interstitial water colloids, surface sample (blue bold line) and water column sample (blue dotted line). Full article ">
Corg./Ntot. (A) and Corg./Ptot. (B) molar ratios ultrafiltrate retentates (UF/0) and permeates (UF/F) using a nominal molecular weight cutoff of 30–10 (UF1), 10–5 (UF2) and <5 kDa (UF3) at the start, after 1 week and after 4 weeks of the degradation experiment. Full article ">
Concentration changes of carbohydrates and proteins during various enzyme hydrolyses (6 hours at 26 °C). Full article ">
FT-IR spectra of the (A) surface and (B) water column macroaggregate matrices, and after (i) α-amylase + β-glucosidase, (ii) protease + proteinase K hydrolysis: carbohydrate bands (region ~1150–900 cm−1), protein bands (region 1654–1635 cm−1), lipid bands (region 2950–2850 cm−1) and inorganic (mineral) components (region <1000 cm−1). Full article ">
FT-IR spectra of the surface macroaggregate matrix and aqueous phase of experimental slurries after α-amylase + β-glucosidase and protease + proteinase K hydrolysis. Full article ">
FT-IR spectra of the surface macroaggregate matrix (sampled at the beginning of the degradation experiment; t1—black line), and after lipase (after 3 weeks at 26 °C, t1—blue line) hydrolysis: carbohydrate bands (region ~1150–900 cm−1), protein bands (region 1654–1635 cm−1), lipid bands (region 2950–2850 cm−1) and inorganic (mineral) components (region <1000 cm−1). Full article ">

481 KiB

Open AccessReview

Marine Polysaccharides in Pharmaceutical Applications: An Overview

by Paola Laurienzo

Mar. Drugs 2010, 8(9), 2435-2465; https://doi.org/10.3390/md8092435 - 2 Sep 2010

Cited by 486 | Viewed by 23322

Abstract

The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to [...] Read more.

The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest. Full article

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188 KiB

Open AccessArticle

Characterization of the Exopolysaccharide Produced by Salipiger mucosus A3^T, a Halophilic Species Belonging to the Alphaproteobacteria, Isolated on the Spanish Mediterranean Seaboard

by Inmaculada Llamas, Juan Antonio Mata, Richard Tallon, Philippe Bressollier, María C. Urdaci, Emilia Quesada and Victoria Béjar

Mar. Drugs 2010, 8(8), 2240-2251; https://doi.org/10.3390/md8082240 - 30 Jul 2010

Cited by 62 | Viewed by 13288

Abstract

We have studied the exopolysaccharide produced by the type strain of Salipiger mucosus, a species of halophilic, EPS-producing (exopolysaccharide-producing) bacterium belonging to the Alphaproteobacteria. The strain, isolated on the Mediterranean seaboard, produced a polysaccharide, mainly during its exponential growth phase but [...] Read more.

We have studied the exopolysaccharide produced by the type strain of Salipiger mucosus, a species of halophilic, EPS-producing (exopolysaccharide-producing) bacterium belonging to the Alphaproteobacteria. The strain, isolated on the Mediterranean seaboard, produced a polysaccharide, mainly during its exponential growth phase but also to a lesser extent during the stationary phase. Culture parameters influenced bacterial growth and EPS production. Yield was always directly related to the quantity of biomass in the culture. The polymer is a heteropolysaccharide with a molecular mass of 250 kDa and its components are glucose (19.7%, w/w), mannose (34%, w/w), galactose (32.9%, w/w) and fucose (13.4%, w/w). Fucose and fucose-rich oligosaccharides have applications in the fields of medicine and cosmetics. The chemical or enzymatic hydrolysis of fucose-rich polysaccharides offers a new efficient way to process fucose. The exopolysaccharide in question produces a solution of very low viscosity that shows pseudoplastic behavior and emulsifying activity on several hydrophobic substrates. It also has a high capacity for binding cations and incorporating considerable quantities of sulfates, this latter feature being very unusual in bacterial polysaccharides. Full article

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326 KiB

Open AccessReview

Prebiotics from Marine Macroalgae for Human and Animal Health Applications

by Laurie O’Sullivan, Brian Murphy, Peter McLoughlin, Patrick Duggan, Peadar G. Lawlor, Helen Hughes and Gillian E. Gardiner

Mar. Drugs 2010, 8(7), 2038-2064; https://doi.org/10.3390/md8072038 - 1 Jul 2010

Cited by 323 | Viewed by 26444

Abstract

The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the [...] Read more.

The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date. Full article

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Distribution of the dominant, sub-dominant and minor components of human fecal microflora. Major dominant phyla are denoted. *: Other components are at the family or genus level (adapted from reference [<a href="#b16-marinedrugs-08-02038" class="html-bibr">16</a>]). Full article ">
Mode of action of prebiotics and purported health benefits in humans and animals. Full article ">
Green seaweed constituents: (a) α-L-rhamnose and (b) glucuronic acid [<a href="#b31-marinedrugs-08-02038" class="html-bibr">31</a>]. Full article ">
Constituent acids of alginic acid, where (a) is β-D-mannuronic acid and (b) is α-L-guluronic acid [<a href="#b43-marinedrugs-08-02038" class="html-bibr">43</a>]. Full article ">
Fucoidan: Branched polysaccharide sulfate ester with L-fucose building blocks as the major component with predominantly α-(1,2) linkages [<a href="#b43-marinedrugs-08-02038" class="html-bibr">43</a>]. Full article ">
Basic chemical units of laminarin, made up of β-(1,3) and β-(1,6) linked glucose. Full article ">
Agar constituents [<a href="#b31-marinedrugs-08-02038" class="html-bibr">31</a>] (R=H or CH3). Full article ">
Basic structure of kappa-, iota-, and lambda-carrageenan [<a href="#b60-marinedrugs-08-02038" class="html-bibr">60</a>]. Full article ">

350 KiB

Open AccessReview

Bacterial Exopolysaccharides from Extreme Marine Habitats: Production, Characterization and Biological Activities

by Annarita Poli, Gianluca Anzelmo and Barbara Nicolaus

Mar. Drugs 2010, 8(6), 1779-1802; https://doi.org/10.3390/md8061779 - 3 Jun 2010

Cited by 312 | Viewed by 22262

Abstract

Many marine bacteria produce exopolysaccharides (EPS) as a strategy for growth, adhering to solid surfaces, and to survive adverse conditions. There is growing interest in isolating new EPS producing bacteria from marine environments, particularly from extreme marine environments such as deep-sea hydrothermal vents [...] Read more.

Many marine bacteria produce exopolysaccharides (EPS) as a strategy for growth, adhering to solid surfaces, and to survive adverse conditions. There is growing interest in isolating new EPS producing bacteria from marine environments, particularly from extreme marine environments such as deep-sea hydrothermal vents characterized by high pressure and temperature and heavy metal presence. Marine EPS-producing microorganisms have been also isolated from several extreme niches such as the cold marine environments typically of Arctic and Antarctic sea ice, characterized by low temperature and low nutrient concentration, and the hypersaline marine environment found in a wide variety of aquatic and terrestrial ecosystems such as salt lakes and salterns. Most of their EPSs are heteropolysaccharides containing three or four different monosaccharides arranged in groups of 10 or less to form the repeating units. These polymers are often linear with an average molecular weight ranging from 1 × 105 to 3 × 105 Da. Some EPS are neutral macromolecules, but the majority of them are polyanionic for the presence of uronic acids or ketal-linked pyruvate or inorganic residues such as phosphate or sulfate. EPSs, forming a layer surrounding the cell, provide an effective protection against high or low temperature and salinity, or against possible predators. By examining their structure and chemical-physical characteristics it is possible to gain insight into their commercial application, and they are employed in several industries. Indeed EPSs produced by microorganisms from extreme habitats show biotechnological promise ranging from pharmaceutical industries, for their immunomodulatory and antiviral effects, bone regeneration and cicatrizing capacity, to food-processing industries for their peculiar gelling and thickening properties. Moreover, some EPSs are employed as biosurfactants and in detoxification mechanisms of petrochemical oil-polluted areas. The aim of this paper is to give an overview of current knowledge on EPSs produced by marine bacteria including symbiotic marine EPS-producing bacteria isolated from some marine annelid worms that live in extreme niches. Full article

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133 KiB

Open AccessCommunication

Anti-Inflammatory Activity of Chitooligosaccharides in Vivo

by João C. Fernandes, Humberto Spindola, Vanessa De Sousa, Alice Santos-Silva, Manuela E. Pintado, Francisco Xavier Malcata and João E. Carvalho

Mar. Drugs 2010, 8(6), 1763-1768; https://doi.org/10.3390/md8061763 - 28 May 2010

Cited by 102 | Viewed by 13455

Abstract

All the reports to date on the anti-inflammatory activity of chitooligosaccharides (COS) are mostly based on in vitro methods. In this work, the anti-inflammatory activity of two COS mixtures is characterized in vivo (using balb/c mice), following the carrageenan-induced paw edema method. This [...] Read more.

All the reports to date on the anti-inflammatory activity of chitooligosaccharides (COS) are mostly based on in vitro methods. In this work, the anti-inflammatory activity of two COS mixtures is characterized in vivo (using balb/c mice), following the carrageenan-induced paw edema method. This is a widely accepted animal model of acute inflammation to evaluate the anti-inflammatory effect of drugs. Our data suggest that COS possess anti-inflammatoryactivity, which is dependent on dose and, at higher doses, also on the molecular weight. A single dose of 500 mg/kg b.w. weight may be suitable to treat acute inflammation cases; however, further studies are needed to ascertain the effect upon longer inflammation periods as well as studies upon the bioavailability of these compounds. Full article

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