Marine Drugs

2024

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18 pages, 2208 KiB

Open AccessArticle

Optimization of Enzymatic Deproteination of Northern Shrimp (Pandalus borealis) Shell Chitin Using Commercial Proteases

by Julia Pohling, Vegneshwaran Vasudevan Ramakrishnan, Abul Hossain, Sheila Trenholm and Deepika Dave

Mar. Drugs 2024, 22(10), 445; https://doi.org/10.3390/md22100445 - 28 Sep 2024

Viewed by 1183

Abstract

Shrimp shells are a key source of chitin, commonly extracted through chemical methods, which may cause minor molecular damage. Nowadays, there is great interest in achieving close to zero protein content in crude chitin in order to use it for high-end markets. Therefore, [...] Read more.

Shrimp shells are a key source of chitin, commonly extracted through chemical methods, which may cause minor molecular damage. Nowadays, there is great interest in achieving close to zero protein content in crude chitin in order to use it for high-end markets. Therefore, this study optimized the enzymatic deproteination using two commercial proteases (SEB Pro FL100 and Sea-B Zyme L200) for effective and fast removal of residual protein from Northern shrimp (Pandalus borealis) shell chitin for the first time. The protein content was determined using both the Kjeldahl method and amino acid analysis using gas chromatography–mass spectrometry (GC-MS). The performance of papain (Sea B Zyme L200) was superior to fungal protease (SEB Pro FL100) for this application, and it achieved residual protein content of 2.01%, while the calculated optimum for the latter enzyme was 6.18%. A model was developed using 2⁴ factorial design, and it was predicted that the lowest residual protein content using fungal protease and papain could be achieved at the following conditions: a pH of 4.2 and 7, and an enzyme concentration of 4 and 1.5%, respectively. Thus, the low-protein content obtained using enzymatic deproteination could be an alternative approach to the traditional methods, indicating their potential to produce premium-quality chitin. Full article

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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

Cited by 1 | Viewed by 1542

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 1233

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 3 | Viewed by 4316

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 9 | Viewed by 2576

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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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 2685

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 13 | Viewed by 3456

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 3 | Viewed by 2931

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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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 19 | Viewed by 2520

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 12 | Viewed by 3048

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 3214

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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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 19 | Viewed by 3896

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 28 | Viewed by 3227

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 20 | Viewed by 3633

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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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 37 | Viewed by 4737

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 40 | Viewed by 7126

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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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 4609

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 4539

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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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 172 | Viewed by 12793

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 167 | Viewed by 9758

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 19 | Viewed by 4863

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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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 24 | Viewed by 3867

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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Graphical abstract

2019

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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 12 | Viewed by 4150

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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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 29 | Viewed by 3176

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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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 28 | Viewed by 5826

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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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 62 | Viewed by 4928

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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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 5828

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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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 34 | Viewed by 4891

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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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 4653

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 348 | Viewed by 16467

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 21 | Viewed by 6198

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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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 4535

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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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 16 | Viewed by 4060

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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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 5146

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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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 35 | Viewed by 4751

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 36 | Viewed by 5214

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 36 | Viewed by 4880

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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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 8617

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 4988

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 59 | Viewed by 7635

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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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 5387

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 23 | Viewed by 4675

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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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 38 | Viewed by 8471

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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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 72 | Viewed by 6750

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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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 72 | Viewed by 7655

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 6118

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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2016

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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 7050

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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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 37 | Viewed by 7612

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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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 44 | Viewed by 7563

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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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 90 | Viewed by 12304

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 8149

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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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 8826

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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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 48 | Viewed by 8025

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 84 | Viewed by 10619

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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