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Mar. Drugs, Volume 11, Issue 11 (November 2013) – 34 articles , Pages 4127-4697

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1275 KiB  
Review
Pathways of Lipid Metabolism in Marine Algae, Co-Expression Network, Bottlenecks and Candidate Genes for Enhanced Production of EPA and DHA in Species of Chromista
by Alice Mühlroth, Keshuai Li, Gunvor Røkke, Per Winge, Yngvar Olsen, Martin F. Hohmann-Marriott, Olav Vadstein and Atle M. Bones
Mar. Drugs 2013, 11(11), 4662-4697; https://doi.org/10.3390/md11114662 - 22 Nov 2013
Cited by 182 | Viewed by 22980
Abstract
The importance of n-3 long chain polyunsaturated fatty acids (LC-PUFAs) for human health has received more focus the last decades, and the global consumption of n-3 LC-PUFA has increased. Seafood, the natural n-3 LC-PUFA source, is harvested beyond a sustainable [...] Read more.
The importance of n-3 long chain polyunsaturated fatty acids (LC-PUFAs) for human health has received more focus the last decades, and the global consumption of n-3 LC-PUFA has increased. Seafood, the natural n-3 LC-PUFA source, is harvested beyond a sustainable capacity, and it is therefore imperative to develop alternative n-3 LC-PUFA sources for both eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Genera of algae such as Nannochloropsis, Schizochytrium, Isochrysis and Phaedactylum within the kingdom Chromista have received attention due to their ability to produce n-3 LC-PUFAs. Knowledge of LC-PUFA synthesis and its regulation in algae at the molecular level is fragmentary and represents a bottleneck for attempts to enhance the n-3 LC-PUFA levels for industrial production. In the present review, Phaeodactylum tricornutum has been used to exemplify the synthesis and compartmentalization of n-3 LC-PUFAs. Based on recent transcriptome data a co-expression network of 106 genes involved in lipid metabolism has been created. Together with recent molecular biological and metabolic studies, a model pathway for n-3 LC-PUFA synthesis in P. tricornutum has been proposed, and is compared to industrialized species of Chromista. Limitations of the n-3 LC-PUFA synthesis by enzymes such as thioesterases, elongases, acyl-CoA synthetases and acyltransferases are discussed and metabolic bottlenecks are hypothesized such as the supply of the acetyl-CoA and NADPH. A future industrialization will depend on optimization of chemical compositions and increased biomass production, which can be achieved by exploitation of the physiological potential, by selective breeding and by genetic engineering. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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521 KiB  
Article
Isolation and Characterization of Collagen and Antioxidant Collagen Peptides from Scales of Croceine Croaker (Pseudosciaena crocea)
by Bin Wang, Yu-Mei Wang, Chang-Feng Chi, Hong-Yu Luo, Shang-Gui Deng and Jian-Yin Ma
Mar. Drugs 2013, 11(11), 4641-4661; https://doi.org/10.3390/md11114641 - 21 Nov 2013
Cited by 149 | Viewed by 13091
Abstract
Acid soluble collagen (ASC) from scales of croceine croaker (ASC-C) was successfully isolated with the yield of 0.37% ± 0.08% (dry weight basis), and characterized as type I collagen on the basis of amino acid analysis and electrophoretic pattern. The antioxidant hydrolysate of [...] Read more.
Acid soluble collagen (ASC) from scales of croceine croaker (ASC-C) was successfully isolated with the yield of 0.37% ± 0.08% (dry weight basis), and characterized as type I collagen on the basis of amino acid analysis and electrophoretic pattern. The antioxidant hydrolysate of ASC-C (ACH) was prepared through a two-stage in vitro digestion (4-h trypsin followed by 4-h pepsin), and three antioxidant peptides (ACH-P1, ACH-P2, and ACH-P3) were further isolated from ACH using ultrafiltration, gel chromatography, and RP-HPLC, and their amino acid sequences were identified as GFRGTIGLVG (ACH-P1), GPAGPAG (ACH-P2), and GFPSG (ACH-P3). ACH-P1, ACH-P2, and ACH-P3 showed good scavenging activities on hydroxyl radical (IC50 0.293, 0.240, and 0.107 mg/mL, respectively), DPPH radical (IC50 1.271, 0.675, and 0.283 mg/mL, respectively), superoxide radical (IC50 0.463, 0.099, and 0.151 mg/mL, respectively), and ABTS radical (IC50 0.421, 0.309, and 0.210 mg/mL, respectively). ACH-P3 was also effectively against lipid peroxidation in the model system. The antioxidant activities of three collagen peptides were due to the presence of hydrophobic amino acid residues within the peptide sequences. The collagen peptides might be used as antioxidant for the therapy of diseases associated with oxidative stress, or reducing oxidative changes during storage. Full article
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766 KiB  
Article
Antiviral Sulfoquinovosyldiacylglycerols (SQDGs) from the Brazilian Brown Seaweed Sargassum vulgare
by Erwan Plouguerné, Lauro M. De Souza, Guilherme L. Sassaki, Jéssica Figueiredo Cavalcanti, Maria Teresa Villela Romanos, Bernardo A. P. Da Gama, Renato Crespo Pereira and Eliana Barreto-Bergter
Mar. Drugs 2013, 11(11), 4628-4640; https://doi.org/10.3390/md11114628 - 21 Nov 2013
Cited by 71 | Viewed by 9183
Abstract
Total lipids from the Brazilian brown seaweed Sargassum vulgare were extracted with chloroform/methanol 2:1 and 1:2 (v/v) at room temperature. After performing Folch partition of the crude lipid extract, the lipids recovered from the Folch lower layer were fractionated on a silica gel [...] Read more.
Total lipids from the Brazilian brown seaweed Sargassum vulgare were extracted with chloroform/methanol 2:1 and 1:2 (v/v) at room temperature. After performing Folch partition of the crude lipid extract, the lipids recovered from the Folch lower layer were fractionated on a silica gel column eluted with chloroform, acetone and methanol. The fraction eluted with methanol, presented a strong orcinol-positive band characteristic of the presence of sulfatides when examined by TLC. This fraction was then purified by two successive silica gel column chromatography giving rise to fractions F4I86 and F4II90 that exhibited strong activity against herpes simplex virus type 1 and 2. The chemical structures present in both fractions were elucidated by ESI-MS and 1H/13C NMR analysis HSQC fingerprints based on their tandem–MS behavior as Sulfoquinovosyldiacylglycerols (SQDGs). The main SQDG present in both fractions and responsible for the anti-herpes activity observed was identified as 1,2-di-O-palmitoyl-3-O-(6-sulfo-α-d-quinovopyranosyl)-glycerol. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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Article
Simultaneous Extraction and Depolymerization of Fucoidan from Sargassum muticum in Aqueous Media
by Elena M. Balboa, Sandra Rivas, Andrés Moure, Herminia Domínguez and Juan Carlos Parajó
Mar. Drugs 2013, 11(11), 4612-4627; https://doi.org/10.3390/md11114612 - 21 Nov 2013
Cited by 93 | Viewed by 10122
Abstract
The biomass components of the invasive seaweed Sargassum muticum were fractionated to allow their separate valorization. S. muticum (Sm) and the solid residue remaining after alginate extraction of this seaweed (AESm) were processed with hot, compressed water (hydrothermal processing) to assess the effects [...] Read more.
The biomass components of the invasive seaweed Sargassum muticum were fractionated to allow their separate valorization. S. muticum (Sm) and the solid residue remaining after alginate extraction of this seaweed (AESm) were processed with hot, compressed water (hydrothermal processing) to assess the effects of temperature on fucoidan solubilization. Fucose-containing oligosaccharides were identified as reaction products. Operating under optimal conditions (170 °C), up to 62 and 85 wt% of the dry mass of Sm and AESm were solubilized, respectively. The reaction media were subjected to precipitation, nanofiltration and freeze-drying. The dried products contained 50% and 85% of the fucoidan present in Sm and AESm, respectively; together with other components such as phenolics and inorganic components. The saccharidic fraction, accounting for up to 35% of the dried extracts, contained fucose as the main sugar, and also galactose, xylose, glucose and mannose. The concentrates were characterized for antioxidant activity using the TEAC assay. Full article
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Review
Bioprospecting Marine Plankton
by Heni Abida, Sandrine Ruchaud, Laurent Rios, Anne Humeau, Ian Probert, Colomban De Vargas, Stéphane Bach and Chris Bowler
Mar. Drugs 2013, 11(11), 4594-4611; https://doi.org/10.3390/md11114594 - 14 Nov 2013
Cited by 56 | Viewed by 15761
Abstract
The ocean dominates the surface of our planet and plays a major role in regulating the biosphere. For example, the microscopic photosynthetic organisms living within provide 50% of the oxygen we breathe, and much of our food and mineral resources are extracted from [...] Read more.
The ocean dominates the surface of our planet and plays a major role in regulating the biosphere. For example, the microscopic photosynthetic organisms living within provide 50% of the oxygen we breathe, and much of our food and mineral resources are extracted from the ocean. In a time of ecological crisis and major changes in our society, it is essential to turn our attention towards the sea to find additional solutions for a sustainable future. Remarkably, while we are overexploiting many marine resources, particularly the fisheries, the planktonic compartment composed of zooplankton, phytoplankton, bacteria and viruses, represents 95% of marine biomass and yet the extent of its diversity remains largely unknown and underexploited. Consequently, the potential of plankton as a bioresource for humanity is largely untapped. Due to their diverse evolutionary backgrounds, planktonic organisms offer immense opportunities: new resources for medicine, cosmetics and food, renewable energy, and long-term solutions to mitigate climate change. Research programs aiming to exploit culture collections of marine micro-organisms as well as to prospect the huge resources of marine planktonic biodiversity in the oceans are now underway, and several bioactive extracts and purified compounds have already been identified. This review will survey and assess the current state-of-the-art and will propose methodologies to better exploit the potential of marine plankton for drug discovery and for dermocosmetics. Full article
(This article belongs to the Collection Bioactive Compounds from Marine Plankton)
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Article
Discovery of New Eunicellin-Based Diterpenoids from a Formosan Soft Coral Cladiella sp.
by Tsung-Hung Chen, Mei-Chin Lu, Yu-Chia Chang, Yin-Di Su, Yu-Hsin Chen, Nai-Cheng Lin, Lee-Shing Fang, Yang-Chang Wu and Ping-Jyun Sung
Mar. Drugs 2013, 11(11), 4585-4593; https://doi.org/10.3390/md11114585 - 14 Nov 2013
Cited by 21 | Viewed by 5811
Abstract
A new eunicellin diterpenoid, cladieunicellin I (1), and a new natural eunicellin, litophynin I diacetate (2), were isolated from a Formosan soft coral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods [...] Read more.
A new eunicellin diterpenoid, cladieunicellin I (1), and a new natural eunicellin, litophynin I diacetate (2), were isolated from a Formosan soft coral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods and by comparison of the spectral data with those of related analogues. Eunicellin 1 exhibited significant cytotoxicity toward the DLD-1 human colorectal adenocarcinoma cells. Full article
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Article
Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells
by Wenxia Sun, Cuiting Lv, Tonghan Zhu, Xue Yang, Shanjian Wei, Jieyin Sun, Kui Hong, Weiming Zhu and Caiguo Huang
Mar. Drugs 2013, 11(11), 4570-4584; https://doi.org/10.3390/md11114570 - 14 Nov 2013
Cited by 32 | Viewed by 7086
Abstract
Multidrug-resistance is a major obstacle facing cancer chemotherapy. This paper demonstrates that novel compound Ophiobolin-O reverses MCF-7/ADR resistance to adriamycin (ADM). The IC50 of ADM treated MCF-7 cells was 2.02 ± 0.05 µM and 74.00 ± 0.18 µM treated MCF-7/ADR cells, about [...] Read more.
Multidrug-resistance is a major obstacle facing cancer chemotherapy. This paper demonstrates that novel compound Ophiobolin-O reverses MCF-7/ADR resistance to adriamycin (ADM). The IC50 of ADM treated MCF-7 cells was 2.02 ± 0.05 µM and 74.00 ± 0.18 µM treated MCF-7/ADR cells, about 37-fold, compared to the former. However, 0.1 µM Ophiobolin-O (less than 20% inhibition concentration) combined with ADM caused the decreased IC50 of ADM to 6.67 ± 0.98 µM, indicating it reversed ADM resistance of MCF-7/ADR cells (11-fold). Furthermore, Ophiobolin-O increased ADM-induced mitochondrial pathway apoptosis and G2/M phase arrest, which is partly due to the elevation level of ROS in MCF-7/ADR cells. As we described in this paper, the reversal effect of Ophiobolin-O may be due to the reduction of resistance-related protein P-Glycoprotein (P-gp, also known as MDR1) through inhibiting the activity of the multidrug resistance 1 (MDR1) gene promoter, which makes MCF-7/ADR cells more sensitive to ADM treatment. Assays in nude mice also showed that the combination of ADM and Ophiobolin-O significantly improved the effect of ADM. Full article
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969 KiB  
Article
Improvement of Neutral Lipid and Polyunsaturated Fatty Acid Biosynthesis by Overexpressing a Type 2 Diacylglycerol Acyltransferase in Marine Diatom Phaeodactylum tricornutum
by Ying-Fang Niu, Meng-Han Zhang, Da-Wei Li, Wei-Dong Yang, Jie-Sheng Liu, Wei-Bin Bai and Hong-Ye Li
Mar. Drugs 2013, 11(11), 4558-4569; https://doi.org/10.3390/md11114558 - 13 Nov 2013
Cited by 221 | Viewed by 11760
Abstract
Microalgae have been emerging as an important source for the production of bioactive compounds. Marine diatoms can store high amounts of lipid and grow quite quickly. However, the genetic and biochemical characteristics of fatty acid biosynthesis in diatoms remain unclear. Glycerophospholipids are integral [...] Read more.
Microalgae have been emerging as an important source for the production of bioactive compounds. Marine diatoms can store high amounts of lipid and grow quite quickly. However, the genetic and biochemical characteristics of fatty acid biosynthesis in diatoms remain unclear. Glycerophospholipids are integral as structural and functional components of cellular membranes, as well as precursors of various lipid mediators. In addition, diacylglycerol acyltransferase (DGAT) is a key enzyme that catalyzes the last step of triacylglyceride (TAG) biosynthesis. However, a comprehensive sequence-structure and functional analysis of DGAT in diatoms is lacking. In this study, an isoform of diacylglycerol acyltransferase type 2 of the marine diatom Phaeodactylum tricornutum was characterized. Surprisingly, DGAT2 overexpression in P. tricornutum stimulated more oil bodies, and the neutral lipid content increased by 35%. The fatty acid composition showed a significant increase in the proportion of polyunsaturated fatty acids; in particular, EPA was increased by 76.2%. Moreover, the growth rate of transgenic microalgae remained similar, thereby maintaining a high biomass. Our results suggest that increased DGAT2 expression could alter fatty acid profile in the diatom, and the results thus represent a valuable strategy for polyunsaturated fatty acid production by genetic manipulation. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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593 KiB  
Article
Antibacterial Activity of Long-Chain Polyunsaturated Fatty Acids against Propionibacterium acnes and Staphylococcus aureus
by Andrew P. Desbois and Keelan C. Lawlor
Mar. Drugs 2013, 11(11), 4544-4557; https://doi.org/10.3390/md11114544 - 13 Nov 2013
Cited by 133 | Viewed by 20632
Abstract
New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections [...] Read more.
New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32–1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15–30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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614 KiB  
Article
Design and Synthesis of Pro-Apoptotic Compounds Inspired by Diatom Oxylipins
by Giovanna Romano, Emiliano Manzo, Gian Luigi Russo, Giuliana D'Ippolito, Adele Cutignano, Maria Russo and Angelo Fontana
Mar. Drugs 2013, 11(11), 4527-4543; https://doi.org/10.3390/md11114527 - 13 Nov 2013
Cited by 8 | Viewed by 6300
Abstract
Oxylipins are a large and diverse family of fatty acid derivatives exhibiting different levels of oxidation of the carbon chain. They are involved in many biological functions in mammals, plants and diatoms. In this last group of organisms, they are suggested to play [...] Read more.
Oxylipins are a large and diverse family of fatty acid derivatives exhibiting different levels of oxidation of the carbon chain. They are involved in many biological functions in mammals, plants and diatoms. In this last group of organisms, they are suggested to play a role in the reproductive failure of copepod predators, showing clear pro-apoptotic effects on newborn nauplii. In this work, these compounds were tested for the ability to induce mitotic arrest in sea urchin embryos. We show for the first time that oxylipins have an increased efficacy in their corresponding methylated form. Natural oxylipins were also used as an inspiration for the rational design and synthesis of stable chemical analogs with apoptotic activity against tumor cell lines. This approach led to the synthesis of the linear C15-ketol (22) that was shown to induce apoptosis in human leukemia U-937 cells. These results are proof of the concept of the use of eco-physiological considerations as a platform to guide the search for novel drug candidates. Full article
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Article
Penicillinolide A: A New Anti-Inflammatory Metabolite from the Marine Fungus Penicillium sp. SF-5292
by Dong-Sung Lee, Wonmin Ko, Tran Hong Quang, Kyoung-Su Kim, Jae Hak Sohn, Jae-Hyuk Jang, Jong Seog Ahn, Youn-Chul Kim and Hyuncheol Oh
Mar. Drugs 2013, 11(11), 4510-4526; https://doi.org/10.3390/md11114510 - 12 Nov 2013
Cited by 34 | Viewed by 7494
Abstract
In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1 [...] Read more.
In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher’s method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-α, IL-1β and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-κB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation. Full article
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Article
Derivatives of Salarin A, Salarin C and Tulearin A—Fascaplysinopsis sp. Metabolites
by Lee Goren Zur, Ashgan Bishara, Maurice Aknin, Drorit Neumann, Nathalie Ben-Califa and Yoel Kashman
Mar. Drugs 2013, 11(11), 4487-4509; https://doi.org/10.3390/md11114487 - 11 Nov 2013
Cited by 7 | Viewed by 7976
Abstract
Derivatives of salarin A, salarin C and tulearin A, three new cytotoxic sponge derived nitrogenous macrolides, were prepared and bio-evaluated as inhibitors of K562 leukemia cells. Interesting preliminary SAR (structure activity relationship) information was obtained from the products. The most sensitive functionalities were [...] Read more.
Derivatives of salarin A, salarin C and tulearin A, three new cytotoxic sponge derived nitrogenous macrolides, were prepared and bio-evaluated as inhibitors of K562 leukemia cells. Interesting preliminary SAR (structure activity relationship) information was obtained from the products. The most sensitive functionalities were the 16,17-vinyl epoxide in both salarins, the triacylamino group in salarin A and the oxazole in salarin C (less sensitive). Regioselectivity of reactions was also found for tulearin A. Full article
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Article
Chlorinated Didemnins from the Tunicate Trididemnum solidum
by Sridevi Ankisetty, Shabana I. Khan, Bharathi Avula, Deborah Gochfeld, Ikhlas A. Khan and Marc Slattery
Mar. Drugs 2013, 11(11), 4478-4486; https://doi.org/10.3390/md11114478 - 11 Nov 2013
Cited by 15 | Viewed by 6241
Abstract
Chemical investigation of the tunicate Trididemnum solidum resulted in the isolation of two new chlorinated compounds belonging to the didemnin class, along with two known compounds didemnin A and didemnin B. The structural determination of the compounds was based on extensive NMR and [...] Read more.
Chemical investigation of the tunicate Trididemnum solidum resulted in the isolation of two new chlorinated compounds belonging to the didemnin class, along with two known compounds didemnin A and didemnin B. The structural determination of the compounds was based on extensive NMR and mass spectroscopic analysis. The isolated compounds 14 were tested for their anti-inflammatory activity using in vitro assays for inhibition of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) activity. The anti-cell proliferative activity of the above compounds was also evaluated against four solid tumor cell lines. Full article
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Article
Isolation and Structural Characterization of a Novel Antioxidant Mannoglucan from a Marine Bubble Snail, Bullacta exarata (Philippi)
by Donghong Liu, Ningbo Liao, Xingqian Ye, Yaqin Hu, Dan Wu, Xin Guo, Jianjun Zhong, Jianyong Wu and Shiguo Chen
Mar. Drugs 2013, 11(11), 4464-4477; https://doi.org/10.3390/md11114464 - 11 Nov 2013
Cited by 17 | Viewed by 8347
Abstract
Bullacta exarata is one of the most economically important aquatic species in China, noted for not only its delicious taste and nutritional value, but also for its pharmacological activities. In order to explore its potential in medical applications, a mannoglucan designated as BEPS-IB [...] Read more.
Bullacta exarata is one of the most economically important aquatic species in China, noted for not only its delicious taste and nutritional value, but also for its pharmacological activities. In order to explore its potential in medical applications, a mannoglucan designated as BEPS-IB was isolated and purified from the foot muscle of B. exarata after papain digestion. Chemical composition analysis indicated BEPS-IB contained mainly d-glucose and d-mannose in a molar ratio of 1:0.52, with an average molecular weight of about 94 kDa. The linkage information was determined by methylation analysis, and the anomeric configuration and chain linkage were confirmed by IR and 2D NMR. The results indicated BEPS-IB was composed of Glcp6Manp heptasaccharide repeating unit in the backbone, with occasional branch chains of mannose residues (14%) occurring in the backbone mannose. Further antioxidant assay indicated BEPS-IB exhibited positive antioxidant activity in scavenging superoxide radicals and reducing power. This is the first report on the structure and bioactivity of the mannoglucan from the B. exarata. Full article
(This article belongs to the Collection Marine Polysaccharides)
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Article
Smenamides A and B, Chlorinated Peptide/Polyketide Hybrids Containing a Dolapyrrolidinone Unit from the Caribbean Sponge Smenospongia aurea. Evaluation of Their Role as Leads in Antitumor Drug Research
by Roberta Teta, Elena Irollo, Gerardo Della Sala, Giuseppe Pirozzi, Alfonso Mangoni and Valeria Costantino
Mar. Drugs 2013, 11(11), 4451-4463; https://doi.org/10.3390/md11114451 - 8 Nov 2013
Cited by 56 | Viewed by 10911
Abstract
An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS [...] Read more.
An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS and homo- and heteronuclear 2D NMR experiments. Structures of smenamides suggested that they are products of the cyanobacterial metabolism, and 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea. Smenamides showed potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, which for compound 1 is exerted through a clear pro-apoptotic mechanism. This makes smenamides promising leads for antitumor drug design. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
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Article
Omega-3 Fatty Acids Modulate Weibel-Palade Body Degranulation and Actin Cytoskeleton Rearrangement in PMA-Stimulated Human Umbilical Vein Endothelial Cells
by Corinna S. Bürgin-Maunder, Peter R. Brooks and Fraser D. Russell
Mar. Drugs 2013, 11(11), 4435-4450; https://doi.org/10.3390/md11114435 - 8 Nov 2013
Cited by 12 | Viewed by 7432
Abstract
Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical [...] Read more.
Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with or without 75 or 120 µM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37 °C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA), and this was assessed by immunocytochemical staining for vWF. Actin reorganization was determined using phalloidin-TRITC staining. We found that PMA stimulated WPB degranulation, and that this was significantly reduced by prior incubation of cells with LC n-3 PUFAs. In these cells, WPBs had rounded rather than rod-shaped morphology and localized to the perinuclear region, suggesting interference with cytoskeletal remodeling that is necessary for complete WPB degranulation. In line with this, actin rearrangement was altered in cells containing perinuclear WPBs, where cells exhibited a thickened actin rim in the absence of prominent cytoplasmic stress fibers. These findings indicate that LC n-3 PUFAs provide some protection against WBP degranulation, and may contribute to an improved understanding of the anti-thrombotic effects previously attributed to LC n-3 PUFAs. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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Article
Crambescidin-816 Acts as a Fungicidal with More Potency than Crambescidin-800 and -830, Inducing Cell Cycle Arrest, Increased Cell Size and Apoptosis in Saccharomyces cerevisiae
by Juan A. Rubiolo, Eva Ternon, Henar López-Alonso, Olivier P. Thomas, Félix V. Vega, Mercedes R. Vieytes and Luis M. Botana
Mar. Drugs 2013, 11(11), 4419-4434; https://doi.org/10.3390/md11114419 - 8 Nov 2013
Cited by 28 | Viewed by 6777
Abstract
In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the [...] Read more.
In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the cell cycle of this yeast. The compound induced cell cycle arrest in G2/M followed by an increase in cell DNA content and size. When the type of cell death was analyzed, we observed that crambescidin-816 induced apoptosis. The antifungal effect indicates that crambescidins, and mostly crambescidin-816, could serve as a lead compound to fight fungal infections. Full article
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502 KiB  
Article
New Constituents from the Korean Sponge Plakortis simplex
by Jung Soon Oh, Buyng Su Hwang, Ok-Hwa Kang, Dong-Yeul Kwon and Jung-Rae Rho
Mar. Drugs 2013, 11(11), 4407-4418; https://doi.org/10.3390/md11114407 - 5 Nov 2013
Cited by 5 | Viewed by 5577
Abstract
Six new cyclic peroxides (16) were isolated from the Korean sponge Plakortis simplex, along with two new alkylpyridinium alkaloids (7 and 8). The structures of these compounds were completely determined by a combination of NMR analysis [...] Read more.
Six new cyclic peroxides (16) were isolated from the Korean sponge Plakortis simplex, along with two new alkylpyridinium alkaloids (7 and 8). The structures of these compounds were completely determined by a combination of NMR analysis and chemical reactions. Compounds 16 exhibited cytotoxic/antifungal activities against RAW264.7 cells and Candida albicans. Full article
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585 KiB  
Article
Antiproliferative Activity of Cyanophora paradoxa Pigments in Melanoma, Breast and Lung Cancer Cells
by Paul-Hubert Baudelet, Anne-Laure Gagez, Jean-Baptiste Bérard, Camille Juin, Nicolas Bridiau, Raymond Kaas, Valérie Thiéry, Jean-Paul Cadoret and Laurent Picot
Mar. Drugs 2013, 11(11), 4390-4406; https://doi.org/10.3390/md11114390 - 1 Nov 2013
Cited by 55 | Viewed by 11859
Abstract
The glaucophyte Cyanophora paradoxa (Cp) was chemically investigated to identify pigments efficiently inhibiting malignant melanoma, mammary carcinoma and lung adenocarcinoma cells growth. Cp water and ethanol extracts significantly inhibited the growth of the three cancer cell lines in vitro, at [...] Read more.
The glaucophyte Cyanophora paradoxa (Cp) was chemically investigated to identify pigments efficiently inhibiting malignant melanoma, mammary carcinoma and lung adenocarcinoma cells growth. Cp water and ethanol extracts significantly inhibited the growth of the three cancer cell lines in vitro, at 100 µg·mL−1. Flash chromatography of the Cp ethanol extract, devoid of c-phycocyanin and allophycocyanin, enabled the collection of eight fractions, four of which strongly inhibited cancer cells growth at 100 µg·mL−1. Particularly, two fractions inhibited more than 90% of the melanoma cells growth, one inducing apoptosis in the three cancer cells lines. The detailed analysis of Cp pigment composition resulted in the discrimination of 17 molecules, ten of which were unequivocally identified by high resolution mass spectrometry. Pheophorbide a, β-cryptoxanthin and zeaxanthin were the three main pigments or derivatives responsible for the strong cytotoxicity of Cp fractions in cancer cells. These data point to Cyanophora paradoxa as a new microalgal source to purify potent anticancer pigments, and demonstrate for the first time the strong antiproliferative activity of zeaxanthin and β-cryptoxanthin in melanoma cells. Full article
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964 KiB  
Review
Bivalve Omics: State of the Art and Potential Applications for the Biomonitoring of Harmful Marine Compounds
by Victoria Suárez-Ulloa, Juan Fernández-Tajes, Chiara Manfrin, Marco Gerdol, Paola Venier and José M. Eirín-López
Mar. Drugs 2013, 11(11), 4370-4389; https://doi.org/10.3390/md11114370 - 1 Nov 2013
Cited by 72 | Viewed by 12966
Abstract
The extraordinary progress experienced by sequencing technologies and bioinformatics has made the development of omic studies virtually ubiquitous in all fields of life sciences nowadays. However, scientific attention has been quite unevenly distributed throughout the different branches of the tree of life, leaving [...] Read more.
The extraordinary progress experienced by sequencing technologies and bioinformatics has made the development of omic studies virtually ubiquitous in all fields of life sciences nowadays. However, scientific attention has been quite unevenly distributed throughout the different branches of the tree of life, leaving molluscs, one of the most diverse animal groups, relatively unexplored and without representation within the narrow collection of well established model organisms. Within this Phylum, bivalve molluscs play a fundamental role in the functioning of the marine ecosystem, constitute very valuable commercial resources in aquaculture, and have been widely used as sentinel organisms in the biomonitoring of marine pollution. Yet, it has only been very recently that this complex group of organisms became a preferential subject for omic studies, posing new challenges for their integrative characterization. The present contribution aims to give a detailed insight into the state of the art of the omic studies and functional information analysis of bivalve molluscs, providing a timely perspective on the available data resources and on the current and prospective applications for the biomonitoring of harmful marine compounds. Full article
(This article belongs to the Special Issue Cytogenetic and Molecular Effects of Marine Compounds)
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404 KiB  
Review
Phylogeny and Biogeography of Cyanobacteria and Their Produced Toxins
by Cristiana Moreira, Vitor Vasconcelos and Agostinho Antunes
Mar. Drugs 2013, 11(11), 4350-4369; https://doi.org/10.3390/md11114350 - 1 Nov 2013
Cited by 54 | Viewed by 8888
Abstract
Phylogeny is an evolutionary reconstruction of the past relationships of DNA or protein sequences and it can further be used as a tool to assess population structuring, genetic diversity and biogeographic patterns. In the microbial world, the concept that everything is everywhere is [...] Read more.
Phylogeny is an evolutionary reconstruction of the past relationships of DNA or protein sequences and it can further be used as a tool to assess population structuring, genetic diversity and biogeographic patterns. In the microbial world, the concept that everything is everywhere is widely accepted. However, it is much debated whether microbes are easily dispersed globally or whether they, like many macro-organisms, have historical biogeographies. Biogeography can be defined as the science that documents the spatial and temporal distribution of a given taxa in the environment at local, regional and continental scales. Speciation, extinction and dispersal are proposed to explain the generation of biogeographic patterns. Cyanobacteria are a diverse group of microorganisms that inhabit a wide range of ecological niches and are well known for their toxic secondary metabolite production. Knowledge of the evolution and dispersal of these microorganisms is still limited, and further research to understand such topics is imperative. Here, we provide a compilation of the most relevant information regarding these issues to better understand the present state of the art as a platform for future studies, and we highlight examples of both phylogenetic and biogeographic studies in non-symbiotic cyanobacteria and cyanotoxins. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
394 KiB  
Review
Okadaic Acid: More than a Diarrheic Toxin
by Vanessa Valdiglesias, María Verónica Prego-Faraldo, Eduardo Pásaro, Josefina Méndez and Blanca Laffon
Mar. Drugs 2013, 11(11), 4328-4349; https://doi.org/10.3390/md11114328 - 31 Oct 2013
Cited by 216 | Viewed by 13826
Abstract
Okadaic acid (OA) is one of the most frequent and worldwide distributed marine toxins. It is easily accumulated by shellfish, mainly bivalve mollusks and fish, and, subsequently, can be consumed by humans causing alimentary intoxications. OA is the main representative diarrheic shellfish poisoning [...] Read more.
Okadaic acid (OA) is one of the most frequent and worldwide distributed marine toxins. It is easily accumulated by shellfish, mainly bivalve mollusks and fish, and, subsequently, can be consumed by humans causing alimentary intoxications. OA is the main representative diarrheic shellfish poisoning (DSP) toxin and its ingestion induces gastrointestinal symptoms, although it is not considered lethal. At the molecular level, OA is a specific inhibitor of several types of serine/threonine protein phosphatases and a tumor promoter in animal carcinogenesis experiments. In the last few decades, the potential toxic effects of OA, beyond its role as a DSP toxin, have been investigated in a number of studies. Alterations in DNA and cellular components, as well as effects on immune and nervous system, and even on embryonic development, have been increasingly reported. In this manuscript, results from all these studies are compiled and reviewed to clarify the role of this toxin not only as a DSP inductor but also as cause of alterations at the cellular and molecular levels, and to highlight the relevance of biomonitoring its effects on human health. Despite further investigations are required to elucidate OA mechanisms of action, toxicokinetics, and harmful effects, there are enough evidences illustrating its toxicity, not related to DSP induction, and, consequently, supporting a revision of the current regulation on OA levels in food. Full article
(This article belongs to the Special Issue Cytogenetic and Molecular Effects of Marine Compounds)
637 KiB  
Article
New Diterpenoids from Soft Coral Sarcophyton ehrenbergi
by Shang-Kwei Wang, Mu-Keng Hsieh and Chang-Yih Duh
Mar. Drugs 2013, 11(11), 4318-4327; https://doi.org/10.3390/md11114318 - 30 Oct 2013
Cited by 30 | Viewed by 6511
Abstract
Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures [...] Read more.
Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, in vitro tests show that compounds 1 and 2 displayed antiviral activity towards human cytomegalovirus, with EC50 of 20 and 8.0 µg/mL, respectively. Full article
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970 KiB  
Article
Anxiolytic-Like Effect of a Salmon Phospholipopeptidic Complex Composed of Polyunsaturated Fatty Acids and Bioactive Peptides
by Nabila Belhaj, Frédéric Desor, Céline Gleizes, Frédéric M. Denis, Elmira Arab-Tehrany, Rachid Soulimani and Michel Linder
Mar. Drugs 2013, 11(11), 4294-4317; https://doi.org/10.3390/md11114294 - 30 Oct 2013
Cited by 13 | Viewed by 7039
Abstract
A phospholipopeptidic complex obtained by the enzymatic hydrolysis of salmon heads in green conditions; exert anxiolytic-like effects in a time and dose-dependent manner, with no affection of locomotor activity. This study focused on the physico-chemical properties of the lipidic and peptidic fractions from [...] Read more.
A phospholipopeptidic complex obtained by the enzymatic hydrolysis of salmon heads in green conditions; exert anxiolytic-like effects in a time and dose-dependent manner, with no affection of locomotor activity. This study focused on the physico-chemical properties of the lipidic and peptidic fractions from this natural product. The characterization of mineral composition, amino acid and fatty acids was carried out. Stability of nanoemulsions allowed us to realize a behavioral study conducted with four different tests on 80 mice. This work highlighted the dose dependent effects of the natural complex and its various fractions over a period of 14 days compared to a conventional anxiolytic. The intracellular redox status of neural cells was evaluated in order to determine the free radicals scavenging potential of these products in the central nervous system (CNS), after mice sacrifice. The complex peptidic fraction showed a strong scavenging property and similar results were found for the complex as well as its lipidic fraction. For the first time, the results of this study showed the anxiolytic-like and neuroprotective properties of a phospholipopeptidic complex extracted from salmon head. The applications on anxiety disorders might be relevant, depending on the doses, the fraction used and the chronicity of the supplementation. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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987 KiB  
Article
Efficient Screening of Marine Extracts for Protease Inhibitors by Combining FRET Based Activity Assays and Surface Plasmon Resonance Spectroscopy Based Binding Assays
by Tony Christopeit, Kersti Øverbø, U. Helena Danielson and Inge W. Nilsen
Mar. Drugs 2013, 11(11), 4279-4293; https://doi.org/10.3390/md11114279 - 30 Oct 2013
Cited by 13 | Viewed by 6116
Abstract
The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the screening process is the generation of false positive hits through unspecific effects from the complex chemical composition of the crude extracts. [...] Read more.
The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the screening process is the generation of false positive hits through unspecific effects from the complex chemical composition of the crude extracts. In this study, we explored a combination of a fluorescence resonance energy transfer (FRET) based activity assay and a surface plasmon resonance (SPR) based binding assay to avoid this problem. An aqueous extract was prepared from rest raw material of the Norwegian spring spawning herring, and further fractionated by methanol solubility and solid phase extraction. FRET based activity assays were used to determine the influence of each extract on the activity of different proteases. Several extracts showed more than 50% inhibition. The inhibition mechanisms were elucidated by SPR based competition experiments with known inhibitors. For the secreted aspartic proteases 1, 2, 3 and HIV-1 protease, the results indicated that some extracts contain inhibitors interacting specifically with the active site of the enzymes. The study shows that a combination of an activity assay and an SPR based binding assay is a powerful tool to identify potent inhibitors in marine extracts. Furthermore, the study shows that marine vertebrates offer an interesting source for new bioactive compounds, although they have rarely been explored for this purpose. Full article
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1177 KiB  
Article
Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma
by Ryuichiro Kimura, Takayoshi Rokkaku, Shinji Takeda, Masachika Senba and Naoki Mori
Mar. Drugs 2013, 11(11), 4267-4278; https://doi.org/10.3390/md11114267 - 30 Oct 2013
Cited by 58 | Viewed by 8680
Abstract
In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell [...] Read more.
In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma. Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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670 KiB  
Article
LC-PUFA-Enriched Oil Production by Microalgae: Accumulation of Lipid and Triacylglycerols Containing n-3 LC-PUFA Is Triggered by Nitrogen Limitation and Inorganic Carbon Availability in the Marine Haptophyte Pavlova lutheri
by Freddy Guihéneuf and Dagmar B. Stengel
Mar. Drugs 2013, 11(11), 4246-4266; https://doi.org/10.3390/md11114246 - 30 Oct 2013
Cited by 104 | Viewed by 11712
Abstract
In most microalgal species, triacyglycerols (TAG) contain mostly saturated and monounsaturated fatty acids, rather than PUFA, while PUFA-enriched oil is the form most desirable for dietary intake. The ability of some species to produce LC-PUFA-enriched oil is currently of specific interest. In this [...] Read more.
In most microalgal species, triacyglycerols (TAG) contain mostly saturated and monounsaturated fatty acids, rather than PUFA, while PUFA-enriched oil is the form most desirable for dietary intake. The ability of some species to produce LC-PUFA-enriched oil is currently of specific interest. In this work, we investigated the role of sodium bicarbonate availability on lipid accumulation and n-3 LC-PUFA partitioning into TAG during batch cultivation of Pavlova lutheri. Maximum growth and nitrate uptake exhibit an optimum concentration and threshold tolerance to bicarbonate addition (~9 mM) above which both parameters decreased. Nonetheless, the transient highest cellular lipid and TAG contents were obtained at 18 mM bicarbonate, immediately after combined alkaline pH stress and nitrate depletion (day nine), while oil body and TAG accumulation were highly repressed with low carbon supply (2 mM). Despite decreases in the proportions of EPA and DHA, maximum volumetric and cellular EPA and DHA contents were obtained at this stage due to accumulation of TAG containing EPA/DHA. TAG accounted for 74% of the total fatty acid per cell, containing 55% and 67% of the overall cellular EPA and DHA contents, respectively. These results clearly demonstrate that inorganic carbon availability and elevated pH represent two limiting factors for lipid and TAG accumulation, as well as n-3 LC-PUFA partitioning into TAG, under nutrient-depleted P. lutheri cultures. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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578 KiB  
Article
Chemical Diversity as a Function of Temperature in Six Northern Diatom Species
by Siv Huseby, Maria Degerlund, Gunilla K. Eriksen, Richard A. Ingebrigtsen, Hans Chr. Eilertsen and Espen Hansen
Mar. Drugs 2013, 11(11), 4232-4245; https://doi.org/10.3390/md11114232 - 30 Oct 2013
Cited by 21 | Viewed by 7405
Abstract
In this study, we investigate how metabolic fingerprints are related to temperature. Six common northern temperate diatoms (Attheya longicornis, Chaetoceros socialis, Chaetoceros furcellatus, Porosira glacialis, Skeletonema marinoi, and Thalassiosira gravida) were cultivated at two different temperatures, [...] Read more.
In this study, we investigate how metabolic fingerprints are related to temperature. Six common northern temperate diatoms (Attheya longicornis, Chaetoceros socialis, Chaetoceros furcellatus, Porosira glacialis, Skeletonema marinoi, and Thalassiosira gravida) were cultivated at two different temperatures, 0.5 and 8.5 °C. To exclude metabolic variations due to differences in growth rates, the growth rates were kept similar by performing the experiments under light limited conditions but in exponential growth phase. Growth rates and maximum quantum yield of photosynthesis were measured and interpreted as physiological variables, and metabolic fingerprints were acquired by high-resolution mass spectrometry. The chemical diversity varied substantially between the two temperatures for the tested species, ranging from 31% similarity for C. furcellatus and P. glacialis to 81% similarity for A. longicornis. The chemical diversity was generally highest at the lowest temperature. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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2471 KiB  
Article
Evidence of Accelerated Evolution and Ectodermal-Specific Expression of Presumptive BDS Toxin cDNAs from Anemonia viridis
by Aldo Nicosia, Teresa Maggio, Salvatore Mazzola and Angela Cuttitta
Mar. Drugs 2013, 11(11), 4213-4231; https://doi.org/10.3390/md11114213 - 30 Oct 2013
Cited by 14 | Viewed by 6558
Abstract
Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging [...] Read more.
Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the β-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple-stranded antiparallel β-sheet and an additional small antiparallel β-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded β-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our cDNA libraries. The calculation of the relative abundance of BDS transcripts in the cDNA libraries revealed that BDS-1, BDS-3, BDS-4, BDS-5 and BDS-6 are the most represented transcripts. Full article
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710 KiB  
Article
Anti-Diabetic Effect of Balanced Deep-Sea Water and Its Mode of Action in High-Fat Diet Induced Diabetic Mice
by Byung Geun Ha, Eun Ji Shin, Jung-Eun Park and Yun Hee Shon
Mar. Drugs 2013, 11(11), 4193-4212; https://doi.org/10.3390/md11114193 - 29 Oct 2013
Cited by 51 | Viewed by 8712
Abstract
In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of [...] Read more.
In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500–2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake. Full article
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