Marine Drugs

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Open AccessArticle

APO-9′-Fucoxanthinone Extracted from Undariopsis peteseniana Protects Oxidative Stress-Mediated Apoptosis in Cigarette Smoke-Exposed Human Airway Epithelial Cells

by Jun-Ho Jang, Ji-Hyeok Lee, Hitendra S. Chand, Jong-Soo Lee, Yong Lin, Nathaniel Weathington, Rama Mallampalli, You-Jin Jeon and Toru Nyunoya

Mar. Drugs 2016, 14(7), 140; https://doi.org/10.3390/md14070140 - 21 Jul 2016

Cited by 11 | Viewed by 6365

Abstract

Long-term cigarette smoking increases the risk for chronic obstructive pulmonary disease (COPD), characterized by irreversible expiratory airflow limitation. The pathogenesis of COPD involves oxidative stress and chronic inflammation. Various natural marine compounds possess both anti-oxidant and anti-inflammatory properties, but few have been tested [...] Read more.

Long-term cigarette smoking increases the risk for chronic obstructive pulmonary disease (COPD), characterized by irreversible expiratory airflow limitation. The pathogenesis of COPD involves oxidative stress and chronic inflammation. Various natural marine compounds possess both anti-oxidant and anti-inflammatory properties, but few have been tested for their efficacy in COPD models. In this study, we conducted an in vitro screening test to identify natural compounds isolated from various brown algae species that might provide protection against cigarette smoke extract (CSE)-induced cytotoxicity. Among nine selected natural compounds, apo-9′-fucoxanthinone (Apo9F) exhibited the highest protection against CSE-induced cytotoxicity in immortalized human bronchial epithelial cells (HBEC2). Furthermore, the protective effects of Apo9F were observed to be associated with a significant reduction in apoptotic cell death, DNA damage, and the levels of mitochondrial reactive oxygen species (ROS) released from CSE-exposed HBEC2 cells. These results suggest that Apo9F protects against CSE-induced DNA damage and apoptosis by regulating mitochondrial ROS production. Full article

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Open AccessReview

Blue-Print Autophagy: Potential for Cancer Treatment

by Nadia Ruocco, Susan Costantini and Maria Costantini

Mar. Drugs 2016, 14(7), 138; https://doi.org/10.3390/md14070138 - 21 Jul 2016

Cited by 30 | Viewed by 8825

Abstract

The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine [...] Read more.

The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine natural products involved in stimulation and inhibition of autophagy (a type of programmed cell death) linked to pharmacological and pathological conditions. Autophagy represents a complex multistep cellular process, wherein a double membrane vesicle (the autophagosome) captures organelles and proteins and delivers them to the lysosome. This natural and destructive mechanism allows the cells to degrade and recycle its cellular components, such as amino acids, monosaccharides, and lipids. Autophagy is an important mechanism used by cells to clear pathogenic organism and deal with stresses. Therefore, it has also been implicated in several diseases, predominantly in cancer. In fact, pharmacological stimulation or inhibition of autophagy have been proposed as approaches to develop new therapeutic treatments of cancers. In conclusion, this blue-print autophagy (so defined because it is induced and/or inhibited by marine natural products) represents a new strategy for the future of biomedicine and of biotechnology in cancer treatment. Full article

(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)

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6280 KiB

Open AccessReview

From Discovery to Production: Biotechnology of Marine Fungi for the Production of New Antibiotics

by Johanna Silber, Annemarie Kramer, Antje Labes and Deniz Tasdemir

Mar. Drugs 2016, 14(7), 137; https://doi.org/10.3390/md14070137 - 21 Jul 2016

Cited by 69 | Viewed by 20807

Abstract

Filamentous fungi are well known for their capability of producing antibiotic natural products. Recent studies have demonstrated the potential of antimicrobials with vast chemodiversity from marine fungi. Development of such natural products into lead compounds requires sustainable supply. Marine biotechnology can significantly contribute [...] Read more.

Filamentous fungi are well known for their capability of producing antibiotic natural products. Recent studies have demonstrated the potential of antimicrobials with vast chemodiversity from marine fungi. Development of such natural products into lead compounds requires sustainable supply. Marine biotechnology can significantly contribute to the production of new antibiotics at various levels of the process chain including discovery, production, downstream processing, and lead development. However, the number of biotechnological processes described for large-scale production from marine fungi is far from the sum of the newly-discovered natural antibiotics. Methods and technologies applied in marine fungal biotechnology largely derive from analogous terrestrial processes and rarely reflect the specific demands of the marine fungi. The current developments in metabolic engineering and marine microbiology are not yet transferred into processes, but offer numerous options for improvement of production processes and establishment of new process chains. This review summarises the current state in biotechnological production of marine fungal antibiotics and points out the enormous potential of biotechnology in all stages of the discovery-to-development pipeline. At the same time, the literature survey reveals that more biotechnology transfer and method developments are needed for a sustainable and innovative production of marine fungal antibiotics. Full article

(This article belongs to the Special Issue Selected Papers from the 1st Congress of Marine Fungal Natural Products Consortium)

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Open AccessArticle

New Cyclotetrapeptides and a New Diketopiperzine Derivative from the Marine Sponge-Associated Fungus Neosartorya glabra KUFA 0702

by War War May Zin, Suradet Buttachon, Tida Dethoup, Carla Fernandes, Sara Cravo, Madalena M. M. Pinto, Luís Gales, José A. Pereira, Artur M. S. Silva, Nazim Sekeroglu and Anake Kijjoa

Mar. Drugs 2016, 14(7), 136; https://doi.org/10.3390/md14070136 - 20 Jul 2016

Cited by 45 | Viewed by 7790

Abstract

Two new cyclotetrapeptides, sartoryglabramides A (5) and B (6), and a new analog of fellutanine A (8) were isolated, together with six known compounds including ergosta-4, 6, 8 (14), 22-tetraen-3-one, ergosterol 5, 8-endoperoxide, helvolic acid, aszonalenin ( [...] Read more.

Two new cyclotetrapeptides, sartoryglabramides A (5) and B (6), and a new analog of fellutanine A (8) were isolated, together with six known compounds including ergosta-4, 6, 8 (14), 22-tetraen-3-one, ergosterol 5, 8-endoperoxide, helvolic acid, aszonalenin (1), (3R)-3-(1H-indol-3-ylmethyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (2), takakiamide (3), (11aR)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (4), and fellutanine A (7), from the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya glabra KUFA 0702. The structures of the new compounds were established based on extensive 1D and 2D spectral analysis. X-ray analysis was also used to confirm the relative configuration of the amino acid constituents of sartoryglabramide A (5), and the absolute stereochemistry of the amino acid constituents of sartoryglabramide A (5) and sartoryglabramides B (6) was determined by chiral HPLC analysis of their hydrolysates by co-injection with the d- and l- amino acids standards. Compounds 1–8 were tested for their antibacterial activity against Gram-positive (Escherichia coli ATCC 25922) and Gram-negative (Staphyllococus aureus ATCC 25923) bacteria, as well as for their antifungal activity against filamentous (Aspergillus fumigatus ATCC 46645), dermatophyte (Trichophyton rubrum ATCC FF5) and yeast (Candida albicans ATCC 10231). None of the tested compounds exhibited either antibacterial (MIC > 256 μg/mL) or antifungal activities (MIC > 512 μg/mL). Full article

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Open AccessArticle

Transcriptome of the Australian Mollusc Dicathais orbita Provides Insights into the Biosynthesis of Indoles and Choline Esters

by Abdul Baten, Ajit Kumar Ngangbam, Daniel L. E. Waters and Kirsten Benkendorff

Mar. Drugs 2016, 14(7), 135; https://doi.org/10.3390/md14070135 - 20 Jul 2016

Cited by 7 | Viewed by 8435

Abstract

Dicathais orbita is a mollusc of the Muricidae family and is well known for the production of the expensive dye Tyrian purple and its brominated precursors that have anticancer properties, in addition to choline esters with muscle-relaxing properties. However, the biosynthetic pathways that [...] Read more.

Dicathais orbita is a mollusc of the Muricidae family and is well known for the production of the expensive dye Tyrian purple and its brominated precursors that have anticancer properties, in addition to choline esters with muscle-relaxing properties. However, the biosynthetic pathways that produce these secondary metabolites in D. orbita are not known. Illumina HiSeq 2000 transcriptome sequencing of hypobranchial glands, prostate glands, albumen glands, capsule glands, and mantle and foot tissues of D. orbita generated over 201 million high quality reads that were de novo assembled into 219,437 contigs. Annotation with reference to the Nr, Swiss-Prot and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases identified candidate-coding regions in 76,152 of these contigs, with transcripts for many enzymes in various metabolic pathways associated with secondary metabolite biosynthesis represented. This study revealed that D. orbita expresses a number of genes associated with indole, sulfur and histidine metabolism pathways that are relevant to Tyrian purple precursor biosynthesis, and many of which were not found in the fully annotated genomes of three other molluscs in the KEGG database. However, there were no matches to known bromoperoxidase enzymes within the D. orbita transcripts. These transcriptome data provide a significant molecular resource for gastropod research in general and Tyrian purple producing Muricidae in particular. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

New Polyketides and New Benzoic Acid Derivatives from the Marine Sponge-Associated Fungus Neosartorya quadricincta KUFA 0081

by Chadaporn Prompanya, Tida Dethoup, Luís Gales, Michael Lee, José A. C. Pereira, Artur M. S. Silva, Madalena M. M. Pinto and Anake Kijjoa

Mar. Drugs 2016, 14(7), 134; https://doi.org/10.3390/md14070134 - 16 Jul 2016

Cited by 26 | Viewed by 7601

Abstract

Two new pentaketides, including a new benzofuran-1-one derivative (1) and a new isochromen-1-one (5), and seven new benzoic acid derivatives, including two new benzopyran derivatives (2a, b), a new benzoxepine derivative (3), two new [...] Read more.

Two new pentaketides, including a new benzofuran-1-one derivative (1) and a new isochromen-1-one (5), and seven new benzoic acid derivatives, including two new benzopyran derivatives (2a, b), a new benzoxepine derivative (3), two new chromen-4-one derivatives (4b, 7) and two new benzofuran derivatives (6a, b), were isolated, together with the previously reported 2,3-dihydro-6-hydroxy-2,2-dimethyl-4H-1-benzopyran-4-one (4a), from the culture of the marine sponge-associated fungus Neosartorya quadricincta KUFA 0081. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis, and in the case of compounds 1, 2a, 4b, 5, 6a and 7, the absolute configurations of their stereogenic carbons were determined by an X-ray crystallographic analysis. None of the isolated compounds were active in the tests for antibacterial activity against Gram-positive and Gram-negative bacteria, as well as multidrug-resistant isolates from the environment (MIC > 256 μg/mL), antifungal activity against yeast (Candida albicans ATTC 10231), filamentous fungus (Aspergillus fumigatus ATTC 46645) and dermatophyte (Trichophyton rubrum FF5) (MIC > 512 µg/mL) and in vitro growth inhibitory activity against the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines (GI₅₀ > 150 µM) by the protein binding dye SRB method. Full article

(This article belongs to the Special Issue Marine Fungal Natural Products)

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Open AccessArticle

Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

by Sergey A. Dyshlovoy, Kseniya M. Tabakmakher, Jessica Hauschild, Regina K. Shchekaleva, Katharina Otte, Alla G. Guzii, Tatyana N. Makarieva, Ekaterina K. Kudryashova, Sergey N. Fedorov, Larisa K. Shubina, Carsten Bokemeyer, Friedemann Honecker, Valentin A. Stonik and Gunhild Von Amsberg

Mar. Drugs 2016, 14(7), 133; https://doi.org/10.3390/md14070133 - 15 Jul 2016

Cited by 48 | Viewed by 8440

Abstract

Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight [...] Read more.

Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1–6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1–4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P⁺ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

Chamigrane Sesquiterpenes from a Basidiomycetous Endophytic Fungus XG8D Associated with Thai Mangrove Xylocarpus granatum

by Siwattra Choodej, Thapong Teerawatananond, Tohru Mitsunaga and Khanitha Pudhom

Mar. Drugs 2016, 14(7), 132; https://doi.org/10.3390/md14070132 - 15 Jul 2016

Cited by 23 | Viewed by 6656

Abstract

Six new chamigrane sesquiterpenes, merulinols A‒F (1‒6), and four known metabolites (7‒10) were isolated from the culture of the basidiomycetous fungus XG8D, a mangrove-derived endophyte. Their structures were elucidated mainly by 1D and 2D NMR, [...] Read more.

Six new chamigrane sesquiterpenes, merulinols A‒F (1‒6), and four known metabolites (7‒10) were isolated from the culture of the basidiomycetous fungus XG8D, a mangrove-derived endophyte. Their structures were elucidated mainly by 1D and 2D NMR, while the structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction analysis. The in vitro cytotoxicity of all compounds was evaluated against three human cancer cell lines, MCF-7, Hep-G2, and KATO-3. Compounds 3 and 4 selectively displayed cytotoxicity against KATO-3 cells with IC₅₀ values of 35.0 and 25.3 μM, respectively. Full article

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Open AccessArticle

Austalides S-U, New Meroterpenoids from the Sponge-Derived Fungus Aspergillus aureolatus HDN14-107

by Jixing Peng, Xiaomin Zhang, Wei Wang, Tianjiao Zhu, Qianqun Gu and Dehai Li

Mar. Drugs 2016, 14(7), 131; https://doi.org/10.3390/md14070131 - 14 Jul 2016

Cited by 32 | Viewed by 7377

Abstract

Three new meroterpenoids, named austalides S-U (1–3), were isolated from the culture of a sponge-derived fungus Aspergillus aureolatus HDN14-107, together with eleven known austalides derivates (4–14). Their structures, including absolute configurations, were assigned on the [...] Read more.

Three new meroterpenoids, named austalides S-U (1–3), were isolated from the culture of a sponge-derived fungus Aspergillus aureolatus HDN14-107, together with eleven known austalides derivates (4–14). Their structures, including absolute configurations, were assigned on the basis of NMR, MS data, and TDDFT ECD calculations. Compound 1 is the first case of austalides with the terpene ring fused to the chroman ring in trans configuration. Compounds 3 and 5 exhibited activities against influenza virus A (H1N1), with IC₅₀ values of 90 and 99 μM, respectively. Full article

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Open AccessArticle

Antiproliferative Scalarane-Based Metabolites from the Red Sea Sponge Hyrtios erectus

by Sameh S. Elhady, Ahmed M. Al-Abd, Ali M. El-Halawany, Abdulrahman M. Alahdal, Hashim A. Hassanean and Safwat A. Ahmed

Mar. Drugs 2016, 14(7), 130; https://doi.org/10.3390/md14070130 - 8 Jul 2016

Cited by 28 | Viewed by 7422

Abstract

Two new sesterterpenes analogs, namely, 12-acetoxy,16-epi-hyrtiolide (1) and 12β-acetoxy,16β-methoxy,20α-hydroxy-17-scalaren-19,20-olide (2), containing a scalarane-based framework along with seven previously reported scalarane-type sesterterpenes (3–9) have been isolated from the sponge Hyrtios erectus (order Dictyoceratida) collected [...] Read more.

Two new sesterterpenes analogs, namely, 12-acetoxy,16-epi-hyrtiolide (1) and 12β-acetoxy,16β-methoxy,20α-hydroxy-17-scalaren-19,20-olide (2), containing a scalarane-based framework along with seven previously reported scalarane-type sesterterpenes (3–9) have been isolated from the sponge Hyrtios erectus (order Dictyoceratida) collected from the Red Sea, Egypt. The structures of the isolated compounds were elucidated on the basis of their spectroscopic data and comparison with reported NMR data. Compounds 1–9 exhibited considerable antiproliferative activity against breast adenocarcinoma (MCF-7), colorectal carcinoma (HCT-116) and hepatocellular carcinoma cells (HepG2). Compounds 3, 5 and 9 were selected for subsequent investigations regarding their mechanism of cell death induction (differential apoptosis/necrosis assessment) and their influence on cell cycle distribution. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessReview

Spotlight on Antimicrobial Metabolites from the Marine Bacteria Pseudoalteromonas: Chemodiversity and Ecological Significance

by Clément Offret, Florie Desriac, Patrick Le Chevalier, Jérôme Mounier, Camille Jégou and Yannick Fleury

Mar. Drugs 2016, 14(7), 129; https://doi.org/10.3390/md14070129 - 8 Jul 2016

Cited by 134 | Viewed by 12038

Abstract

This review is dedicated to the antimicrobial metabolite-producing Pseudoalteromonas strains. The genus Pseudoalteromonas hosts 41 species, among which 16 are antimicrobial metabolite producers. To date, a total of 69 antimicrobial compounds belonging to 18 different families have been documented. They are classified into [...] Read more.

This review is dedicated to the antimicrobial metabolite-producing Pseudoalteromonas strains. The genus Pseudoalteromonas hosts 41 species, among which 16 are antimicrobial metabolite producers. To date, a total of 69 antimicrobial compounds belonging to 18 different families have been documented. They are classified into alkaloids, polyketides, and peptides. Finally as Pseudoalteromonas strains are frequently associated with macroorganisms, we can discuss the ecological significance of antimicrobial Pseudoalteromonas as part of the resident microbiota. Full article

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Open AccessReview

To Pee, or Not to Pee: A Review on Envenomation and Treatment in European Jellyfish Species

by Louise Montgomery, Jan Seys and Jan Mees

Mar. Drugs 2016, 14(7), 127; https://doi.org/10.3390/md14070127 - 8 Jul 2016

Cited by 41 | Viewed by 24877

Abstract

There is a growing cause for concern on envenoming European species because of jellyfish blooms, climate change and globalization displacing species. Treatment of envenomation involves the prevention of further nematocyst release and relieving local and systemic symptoms. Many anecdotal treatments are available but [...] Read more.

There is a growing cause for concern on envenoming European species because of jellyfish blooms, climate change and globalization displacing species. Treatment of envenomation involves the prevention of further nematocyst release and relieving local and systemic symptoms. Many anecdotal treatments are available but species-specific first aid response is essential for effective treatment. However, species identification is difficult in most cases. There is evidence that oral analgesics, seawater, baking soda slurry and 42–45 °C hot water are effective against nematocyst inhibition and giving pain relief. The application of topical vinegar for 30 s is effective on stings of specific species. Treatments, which produce osmotic or pressure changes can exacerbate the initial sting and aggravate symptoms, common among many anecdotal treatments. Most available therapies are based on weak evidence and thus it is strongly recommended that randomized clinical trials are undertaken. We recommend a vital increase in directed research on the effect of environmental factors on envenoming mechanisms and to establish a species-specific treatment. Adequate signage on jellyfish stings and standardized first aid protocols with emphasis on protective equipment and avoidance of jellyfish to minimize cases should be implemented in areas at risk. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

Screening of Diatom Strains and Characterization of Cyclotella cryptica as A Potential Fucoxanthin Producer

by Bingbing Guo, Bin Liu, Bo Yang, Peipei Sun, Xue Lu, Jin Liu and Feng Chen

Mar. Drugs 2016, 14(7), 125; https://doi.org/10.3390/md14070125 - 8 Jul 2016

Cited by 100 | Viewed by 11982

Abstract

Fucoxanthin has been receiving ever-increasing interest due to its broad health beneficial effects. Currently, seaweeds are the predominant source of natural fucoxanthin. However, the disappointingly low fucoxanthin content has impeded their use, driving the exploration of alternative fucoxanthin producers. In the present study, [...] Read more.

Fucoxanthin has been receiving ever-increasing interest due to its broad health beneficial effects. Currently, seaweeds are the predominant source of natural fucoxanthin. However, the disappointingly low fucoxanthin content has impeded their use, driving the exploration of alternative fucoxanthin producers. In the present study, thirteen diatom strains were evaluated with respect to growth and fucoxanthin production potential. Cyclotella cryptica (CCMP 333), which grew well for fucoxanthin production under both photoautotrophic and heterotrophic growth conditions, was selected for further investigation. The supply of nitrate and light individually or in combination were all found to promote growth and fucoxanthin accumulation. When transferring heterotrophic cultures to light, fucoxanthin responded differentially to light intensities and was impaired by higher light intensity with a concomitant increase in diadinoxanthin and diatoxanthin, indicative of the modulation of Diadinoxanthin Cycle to cope with the light stress. Taken together, we, for the first time, performed the screening of diatom strains for fucoxanthin production potential and investigated in detail the effect of nutritional and environmental factors on C. cryptica growth and fucoxanthin accumulation. These results provide valuable implications into future engineering of C. cryptica culture parameters for improved fucoxanthin production and C. cryptica may emerge as a promising microalgal source of fucoxanthin. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Plankton)

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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 8140

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

(This article belongs to the Collection Marine Polysaccharides)

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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 8810

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

(This article belongs to the Collection Marine Polysaccharides)

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Open AccessArticle

Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum

by Nadja A. Henke, Sabine A. E. Heider, Petra Peters-Wendisch and Volker F. Wendisch

Mar. Drugs 2016, 14(7), 124; https://doi.org/10.3390/md14070124 - 30 Jun 2016

Cited by 89 | Viewed by 13711

Abstract

Astaxanthin, a red C40 carotenoid, is one of the most abundant marine carotenoids. It is currently used as a food and feed additive in a hundred-ton scale and is furthermore an attractive component for pharmaceutical and cosmetic applications with antioxidant activities. Corynebacterium glutamicum [...] Read more.

Astaxanthin, a red C40 carotenoid, is one of the most abundant marine carotenoids. It is currently used as a food and feed additive in a hundred-ton scale and is furthermore an attractive component for pharmaceutical and cosmetic applications with antioxidant activities. Corynebacterium glutamicum, which naturally synthesizes the yellow C50 carotenoid decaprenoxanthin, is an industrially relevant microorganism used in the million-ton amino acid production. In this work, engineering of a genome-reduced C. glutamicum with optimized precursor supply for astaxanthin production is described. This involved expression of heterologous genes encoding for lycopene cyclase CrtY, β-carotene ketolase CrtW, and hydroxylase CrtZ. For balanced expression of crtW and crtZ their translation initiation rates were varied in a systematic approach using different ribosome binding sites, spacing, and translational start codons. Furthermore, β-carotene ketolases and hydroxylases from different marine bacteria were tested with regard to efficient astaxanthin production in C. glutamicum. In shaking flasks, the C. glutamicum strains developed here overproduced astaxanthin with volumetric productivities up to 0.4 mg·L⁻¹·h⁻¹ which are competitive with current algae-based production. Since C. glutamicum can grow to high cell densities of up to 100 g cell dry weight (CDW)·L⁻¹, the recombinant strains developed here are a starting point for astaxanthin production by C. glutamicum. Full article

(This article belongs to the Special Issue Marine Carotenoids)

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Open AccessArticle

Structural Features and Potent Antidepressant Effects of Total Sterols and β-sitosterol Extracted from Sargassum horneri

by Donghai Zhao, Lianwen Zheng, Ling Qi, Shuran Wang, Liping Guan, Yanan Xia and Jianhui Cai

Mar. Drugs 2016, 14(7), 123; https://doi.org/10.3390/md14070123 - 28 Jun 2016

Cited by 53 | Viewed by 11599

Abstract

The purified total sterols and β-sitosterol extracted from Sargassum horneri were evaluated for their antidepressant-like activity using the forced swim test (FST) and tail suspension test (TST) in mice. Total sterols and β-sitosterol significantly reduced the immobility time in the FST and TST. [...] Read more.

The purified total sterols and β-sitosterol extracted from Sargassum horneri were evaluated for their antidepressant-like activity using the forced swim test (FST) and tail suspension test (TST) in mice. Total sterols and β-sitosterol significantly reduced the immobility time in the FST and TST. Total sterols were administered orally for 7 days at doses of 50, 100, and 200 mg/kg, and β-sitosterol was administered intraperitoneally at doses of 10, 20, and 30 mg/kg. β-sitosterol had no effect on locomotor activity in the open field test. In addition, total sterols and β-sitosterol significantly increased NE, 5-HT, and the metabolite 5-HIAA in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters. Full article

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Open AccessArticle

Pretrichodermamides D–F from a Marine Algicolous Fungus Penicillium sp. KMM 4672

by Anton N. Yurchenko, Olga F. Smetanina, Elena V. Ivanets, Anatoly I. Kalinovsky, Yuliya V. Khudyakova, Natalya N. Kirichuk, Roman S. Popov, Carsten Bokemeyer, Gunhild Von Amsberg, Ekaterina A. Chingizova, Shamil Sh. Afiyatullov and Sergey A. Dyshlovoy

Mar. Drugs 2016, 14(7), 122; https://doi.org/10.3390/md14070122 - 27 Jun 2016

Cited by 40 | Viewed by 7478

Abstract

Three new epidithiodiketopiperazines pretrichodermamides D–F (1–3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide С (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures [...] Read more.

Three new epidithiodiketopiperazines pretrichodermamides D–F (1–3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide С (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures of compounds 1–5 were determined based on spectroscopic methods. The absolute configuration of pretrichodermamide D (1) was established by a combination of modified Mosher′s method, NOESY data, and biogenetic considerations. N-Methylpretrichodermamide B (5) showed strong cytotoxicity against 22Rv1 human prostate cancer cells resistant to androgen receptor targeted therapies. Full article

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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 47 | Viewed by 8006

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

(This article belongs to the Collection Marine Polysaccharides)

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Mar. Drugs, Volume 14, Issue 7 (July 2016) – 19 articles

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