Marine Drugs

651 KiB

Open AccessArticle

Production of Hyaluronic Acid by Streptococcus zooepidemicus on Protein Substrates Obtained from Scyliorhinus canicula Discards

by José A. Vázquez, Lorenzo Pastrana, Carmen Piñeiro, José A. Teixeira, Ricardo I. Pérez-Martín and Isabel R. Amado

Mar. Drugs 2015, 13(10), 6537-6549; https://doi.org/10.3390/md13106537 - 23 Oct 2015

Cited by 37 | Viewed by 9699

Abstract

This work investigates the production of hyaluronic acid (H) by Streptococcus equi subsp. zooepidemicus in complex media formulated with peptones obtained from Scyliorhinus canicula viscera by-products. Initially, in batch cultures, the greatest productions were achieved using commercial media (3.03 g/L) followed by peptones [...] Read more.

This work investigates the production of hyaluronic acid (H) by Streptococcus equi subsp. zooepidemicus in complex media formulated with peptones obtained from Scyliorhinus canicula viscera by-products. Initially, in batch cultures, the greatest productions were achieved using commercial media (3.03 g/L) followed by peptones from alcalase hydrolyzed viscera (2.32 g/L) and peptones from non-hydrolyzed viscera (2.26 g/L). An increase of between 12% and 15% was found in subsequent fed-batch cultures performed on waste peptones. Such organic nitrogen sources were shown to be an excellent low-cost substrate for microbial H, saving more than 50% of the nutrient costs. Full article

(This article belongs to the Special Issue Marine Glycoconjugates)

► Show Figures

Graphical abstract

1321 KiB

Open AccessArticle

Simultaneous Determination of Fucoxanthin and Its Deacetylated Metabolite Fucoxanthinol in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry

by Yiping Zhang, Hao Wu, Hongmei Wen, Hua Fang, Zhuan Hong, Ruizao Yi and Rui Liu

Mar. Drugs 2015, 13(10), 6521-6536; https://doi.org/10.3390/md13106521 - 23 Oct 2015

Cited by 39 | Viewed by 7085

Abstract

Fucoxanthin and its deacetylated metabolite fucoxanthinol are two major carotenoids that have been confirmed to possess various pharmacological properties. In the present study, fucoxanthinol was identified as the deacetylated metabolite of fucoxanthin, after intravenous (i.v.) and intragastric gavage (i.g.) administration to rats at [...] Read more.

Fucoxanthin and its deacetylated metabolite fucoxanthinol are two major carotenoids that have been confirmed to possess various pharmacological properties. In the present study, fucoxanthinol was identified as the deacetylated metabolite of fucoxanthin, after intravenous (i.v.) and intragastric gavage (i.g.) administration to rats at doses of 2 and 65 mg/kg, respectively, by liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. Next, an accurate and precise LC-MS/MS method was developed to quantitatively determine fucoxanthin and fucoxanthinol in rat plasma. Plasma samples were resolved by LC-MS/MS on a reverse-phase SB-C18 column that was equilibrated and eluted with acetonitrile (A)/aqueous 0.1% formic acid (B; 92/8, v/v) at a flow rate of 0.5 mL/min. Analytes were monitored by multiple-reaction monitoring (MRM) under positive electrospray ionization mode. The precursor/product transitions (m/z) were 659.3→109.0 for fucoxanthin, 617.2→109.0 for fucoxanthinol, and 429.4→313.2 for the internal standard (IS). Calibration curves for fucoxanthin and fucoxanthinol were linear over concentrations ranging from 1.53 to 720 and 1.17 to 600 ng/mL, respectively. The inter- and intraday accuracy and precision were within ±15%. The method was applied successfully in a pharmacokinetic study and the resulting oral fucoxanthin bioavailability calculated. Full article

(This article belongs to the Special Issue Marine Natural Products that Target Metabolic Disorders)

► Show Figures

Graphical abstract

357 KiB

Open AccessReview

Cell Death Inducing Microbial Protein Phosphatase Inhibitors—Mechanisms of Action

by Rune Kleppe, Lars Herfindal and Stein Ove Døskeland

Mar. Drugs 2015, 13(10), 6505-6520; https://doi.org/10.3390/md13106505 - 22 Oct 2015

Cited by 17 | Viewed by 7212

Abstract

Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the major serine/threonine protein phosphatases. This review summarizes mechanisms [...] Read more.

Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the major serine/threonine protein phosphatases. This review summarizes mechanisms believed to be responsible for the death induction and tumor promotion with focus on the interdependent production of reactive oxygen species (ROS) and activation of Ca²⁺/calmodulin kinase II (CaM-KII). New data are presented using inhibitors of specific ROS producing enzymes to curb nodularin/MC-induced liver cell (hepatocyte) death. They indicate that enzymes of the arachidonic acid pathway, notably phospholipase A2, 5-lipoxygenase, and cyclooxygenases, may be required for nodularin/MC-induced (and presumably OA-induced) cell death, suggesting new ways to overcome at least some aspects of OA and MC toxicity. Full article

► Show Figures

Graphical abstract

1182 KiB

Open AccessArticle

Alkaloids with Cardiovascular Effects from the Marine-Derived Fungus Penicillium expansum Y32

by Ya-Qin Fan, Pei-Hai Li, Ya-Xi Chao, Hao Chen, Ning Du, Qiu-Xia He and Ke-Chun Liu

Mar. Drugs 2015, 13(10), 6489-6504; https://doi.org/10.3390/md13106489 - 22 Oct 2015

Cited by 46 | Viewed by 7848

Abstract

Three new alkaloids (1, 4 and 8), together with nine known analogues (2, 3, 5–7, and 9–12), were isolated from the marine-derived fungus Penicillium expansum Y32. Their structures including the absolute configurations were elucidated by spectroscopic and Mosher’s and Marfey’s methods, along with [...] Read more.

Three new alkaloids (1, 4 and 8), together with nine known analogues (2, 3, 5–7, and 9–12), were isolated from the marine-derived fungus Penicillium expansum Y32. Their structures including the absolute configurations were elucidated by spectroscopic and Mosher’s and Marfey’s methods, along with quantum electronic circular dichroism (ECD) calculations. Each of the compounds was evaluated for cardiovascular effects in a live zebrafish model. All of the compounds showed a significant mitigative effect on bradycardia caused by astemizole (ASM) in the heart rate experiments. Compounds 4–6 and 8–12 exhibited potent vasculogenetic activity in vasculogenesis experiments. This is the first study to report that these types of compounds show cardiovascular effects in zebrafish. The results suggest that these compounds could be promising candidates for cardiovascular disease lead compounds. Full article

(This article belongs to the Special Issue Marine Secondary Metabolites)

► Show Figures

Graphical abstract

1762 KiB

Open AccessArticle

Matrix Production, Pigment Synthesis, and Sporulation in a Marine Isolated Strain of Bacillus pumilus

by Blanda Di Luccia, Antonio Riccio, Adele Vanacore, Loredana Baccigalupi, Antonio Molinaro and Ezio Ricca

Mar. Drugs 2015, 13(10), 6472-6488; https://doi.org/10.3390/md13106472 - 21 Oct 2015

Cited by 5 | Viewed by 7523

Abstract

The ability to produce an extracellular matrix and form multicellular communities is an adaptive behavior shared by many bacteria. In Bacillus subtilis, the model system for spore-forming bacteria, matrix production is one of the possible differentiation pathways that a cell can follow [...] Read more.

The ability to produce an extracellular matrix and form multicellular communities is an adaptive behavior shared by many bacteria. In Bacillus subtilis, the model system for spore-forming bacteria, matrix production is one of the possible differentiation pathways that a cell can follow when vegetative growth is no longer feasible. While in B. subtilis the genetic system controlling matrix production has been studied in detail, it is still unclear whether other spore formers utilize similar mechanisms. We report that SF214, a pigmented strain of Bacillus pumilus isolated from the marine environment, can produce an extracellular matrix relying on orthologs of many of the genes known to be important for matrix synthesis in B. subtilis. We also report a characterization of the carbohydrates forming the extracellular matrix of strain SF214. The isolation and characterization of mutants altered in matrix synthesis, pigmentation, and spore formation suggest that in strain SF214 the three processes are strictly interconnected and regulated by a common molecular mechanism. Full article

(This article belongs to the Special Issue Marine Glycoconjugates)

► Show Figures

Graphical abstract

312 KiB

Open AccessArticle

Effect of Solvent System on Extractability of Lipidic Components of Scenedesmus obliquus (M2-1) and Gloeothece sp. on Antioxidant Scavenging Capacity Thereof

by Helena M. Amaro, Fátima Fernandes, Patrícia Valentão, Paula B. Andrade, I. Sousa-Pinto, F. Xavier Malcata and A. Catarina Guedes

Mar. Drugs 2015, 13(10), 6453-6471; https://doi.org/10.3390/md13106453 - 20 Oct 2015

Cited by 69 | Viewed by 7153

Abstract

Microalgae are well known for their biotechnological potential, namely with regard to bioactive lipidic components—especially carotenoids and polyunsaturated fatty acids (PUFA), well-known for therapeutic applications based on their antioxidant capacity. The aim of this work was to evaluate the influence of four distinct [...] Read more.

Microalgae are well known for their biotechnological potential, namely with regard to bioactive lipidic components—especially carotenoids and polyunsaturated fatty acids (PUFA), well-known for therapeutic applications based on their antioxidant capacity. The aim of this work was to evaluate the influence of four distinct food-grade solvents upon extractability of specific lipidic components, and on the antioxidant capacity exhibited against both synthetic (2,2-diphenyl-1-picrylhydrazyl (DPPH^•) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS^+•)) and biological reactive species (O₂^•^- and ^•NO^-). A eukaryotic microalga (Scenedesmus obliquus (M2-1)) and a prokaryotic one (Gloeothece sp.) were used as case studies. Concerning total antioxidant capacity, the hexane:isopropanol (3:2) and acetone extracts of Sc. obliquus (M2-1) were the most effective against DPPH^• and ABTS^+•, respectively. Gloeothece sp. ethanol extracts were the most interesting scavengers of O₂^•^-, probably due the high content of linolenic acid. On the other hand, acetone and hexane:isopropanol (3:2) extracts were the most interesting ones in ^•NO^- assay. Acetone extract exhibited the best results for the ABTS assay, likely associated to its content of carotenoids, in both microalgae. Otherwise, ethanol stood out in PUFA extraction. Therefore, profiles of lipidic components extracted are critical for evaluating the antioxidant performance—which appears to hinge, in particular, on the balance between carotenoids and PUFAs. Full article

(This article belongs to the Special Issue Marine Carotenoids and Oxidative Stress)

► Show Figures

Graphical abstract

225 KiB

Open AccessArticle

Assessment of the Antimicrobial Activity of Algae Extracts on Bacteria Responsible of External Otitis

by Gianluca Pane, Gabriele Cacciola, Elisabetta Giacco, Gian Luigi Mariottini and Erika Coppo

Mar. Drugs 2015, 13(10), 6440-6452; https://doi.org/10.3390/md13106440 - 20 Oct 2015

Cited by 49 | Viewed by 8363

Abstract

External otitis is a diffuse inflammation around the external auditory canal and auricle, which is often occurred by microbial infection. This disease is generally treated using antibiotics, but the frequent occurrence of antibiotic resistance requires the development of new antibiotic agents. In this [...] Read more.

External otitis is a diffuse inflammation around the external auditory canal and auricle, which is often occurred by microbial infection. This disease is generally treated using antibiotics, but the frequent occurrence of antibiotic resistance requires the development of new antibiotic agents. In this context, unexplored bioactive natural candidates could be a chance for the production of targeted drugs provided with antimicrobial activity. In this paper, microbial pathogens were isolated from patients with external otitis using ear swabs for over one year, and the antimicrobial activity of the two methanol extracts from selected marine (Dunaliella salina) and freshwater (Pseudokirchneriella subcapitata) microalgae was tested on the isolated pathogens. Totally, 114 bacterial and 11 fungal strains were isolated, of which Staphylococcus spp. (28.8%) and Pseudomonas aeruginosa (P. aeruginosa) (24.8%) were the major pathogens. Only three Staphylococcus aureus (S. aureus) strains and 11 coagulase-negative Staphylococci showed resistance to methicillin. The two algal extracts showed interesting antimicrobial properties, which mostly inhibited the growth of isolated S. aureus, P. aeruginosa, Escherichia coli, and Klebsiella spp. with MICs range of 1.4 × 10⁹ to 2.2 × 10¹⁰ cells/mL. These results suggest that the two algae have potential as resources for the development of antimicrobial agents. Full article

► Show Figures

Graphical abstract

951 KiB

Open AccessArticle

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

by Ariela Burg and Levy-Ontman Oshrat

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

Cited by 12 | Viewed by 6512

Abstract

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

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

(This article belongs to the Collection Marine Polysaccharides)

► Show Figures

Figure 1

1082 KiB

Open AccessArticle

A Cultivated Form of a Red Seaweed (Chondrus crispus), Suppresses β-Amyloid-Induced Paralysis in Caenorhabditis elegans

by Jatinder Singh Sangha, Owen Wally, Arjun H. Banskota, Roumiana Stefanova, Jeff T. Hafting, Alan T. Critchley and Balakrishnan Prithiviraj

Mar. Drugs 2015, 13(10), 6407-6424; https://doi.org/10.3390/md13106407 - 20 Oct 2015

Cited by 19 | Viewed by 6510

Abstract

We report here the protective effects of a methanol extract from a cultivated strain of the red seaweed, Chondrus crispus, against β-amyloid-induced toxicity, in a transgenic Caenorhabditis elegans, expressing human Aβ_1-42 gene. The methanol extract of C. crispus (CCE), delayed β-amyloid-induced [...] Read more.

We report here the protective effects of a methanol extract from a cultivated strain of the red seaweed, Chondrus crispus, against β-amyloid-induced toxicity, in a transgenic Caenorhabditis elegans, expressing human Aβ_1-42 gene. The methanol extract of C. crispus (CCE), delayed β-amyloid-induced paralysis, whereas the water extract (CCW) was not effective. The CCE treatment did not affect the transcript abundance of amy1; however, Western blot analysis revealed a significant decrease of Aβ species, as compared to untreated worms. The transcript abundance of stress response genes; sod3, hsp16.2 and skn1 increased in CCE-treated worms. Bioassay guided fractionation of the CCE yielded a fraction enriched in monogalactosyl diacylglycerols (MGDG) that significantly delayed the onset of β-amyloid-induced paralysis. Taken together, these results suggested that the cultivated strain of C. crispus, whilst providing dietary nutritional value, may also have significant protective effects against β-amyloid-induced toxicity in C. elegans, partly through reduced β-amyloid species, up-regulation of stress induced genes and reduced accumulation of reactive oxygen species (ROS). Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

► Show Figures

Graphical abstract

312 KiB

Open AccessReview

Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses

by Jorge Lago, Laura P. Rodríguez, Lucía Blanco, Juan Manuel Vieites and Ana G. Cabado

Mar. Drugs 2015, 13(10), 6384-6406; https://doi.org/10.3390/md13106384 - 19 Oct 2015

Cited by 191 | Viewed by 33968

Abstract

Tetrodotoxin (TTX) is a potent neurotoxin responsible for many human intoxications and fatalities each year. The origin of TTX is unknown, but in the pufferfish, it seems to be produced by endosymbiotic bacteria that often seem to be passed down the food chain. [...] Read more.

Tetrodotoxin (TTX) is a potent neurotoxin responsible for many human intoxications and fatalities each year. The origin of TTX is unknown, but in the pufferfish, it seems to be produced by endosymbiotic bacteria that often seem to be passed down the food chain. The ingestion of contaminated pufferfish, considered the most delicious fish in Japan, is the usual route of toxicity. This neurotoxin, reported as a threat to human health in Asian countries, has spread to the Pacific and Mediterranean, due to the increase of temperature waters worldwide. TTX, for which there is no known antidote, inhibits sodium channel producing heart failure in many cases and consequently death. In Japan, a regulatory limit of 2 mg eq TTX/kg was established, although the restaurant preparation of “fugu” is strictly controlled by law and only chefs qualified are allowed to prepare the fish. Due to its paralysis effect, this neurotoxin could be used in the medical field as an analgesic to treat some cancer pains. Full article

► Show Figures

Graphical abstract

2273 KiB

Open AccessReview

Recent Advances in Drug Discovery from South African Marine Invertebrates

by Michael T. Davies-Coleman and Clinton G. L. Veale

Mar. Drugs 2015, 13(10), 6366-6383; https://doi.org/10.3390/md13106366 - 14 Oct 2015

Cited by 15 | Viewed by 6739

Abstract

Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin [...] Read more.

Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin and mandelalides (from C. gilchristi and Lissoclinum sp., respectively) and various analogues are presented. The threat of drug-resistant pathogens, e.g., methicillin-resistant Staphylococcus aureus (MRSA), is assuming greater global significance, and medicinal chemistry strategies to exploit the potent MRSA PK inhibition, first revealed by two marine secondary metabolites, cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin from T. pachastrelloides, are compared. Full article

(This article belongs to the Special Issue Marine Bioactive Natural Product Studies—A Southern Hemisphere Perspective)

► Show Figures

Graphical abstract

1061 KiB

Open AccessArticle

Spiromastixones Inhibit Foam Cell Formation via Regulation of Cholesterol Efflux and Uptake in RAW264.7 Macrophages

by Chongming Wu, Ran Chen, Mingyue Liu, Dong Liu, Xin Li, Shuai Wang, Siwen Niu, Peng Guo and Wenhan Lin

Mar. Drugs 2015, 13(10), 6352-6365; https://doi.org/10.3390/md13106352 - 14 Oct 2015

Cited by 33 | Viewed by 6876

Abstract

Bioassay-guided evaluation shows that a deep sea-derived fungus, Spiromastix sp. MCCC 3A00308, possesses lipid-lowering activity. Chromatographic separation of a culture broth resulted in the isolation of 15 known depsidone-based analogues, labeled spiromastixones A–O (1–15). Each of these compounds [...] Read more.

Bioassay-guided evaluation shows that a deep sea-derived fungus, Spiromastix sp. MCCC 3A00308, possesses lipid-lowering activity. Chromatographic separation of a culture broth resulted in the isolation of 15 known depsidone-based analogues, labeled spiromastixones A–O (1–15). Each of these compounds was tested for its ability to inhibit oxidized low-density lipoprotein (oxLDL)-induced foam cell formation in RAW264.7 macrophages. Spiromastixones 6–8 and 12–14 significantly decreased oxLDL-induced lipid over-accumulation, reduced cell surface area, and reduced intracellular cholesterol concentration. Of these compounds, spiromastixones 6 and 14 exerted the strongest inhibitory effects. Spiromastixones 6 and 14 dramatically inhibited cholesterol uptake and stimulated cholesterol efflux to apolipoprotein A1 (ApoA1) and high-density lipoprotein (HDL) in RAW264.7 macrophages. Mechanistic investigation indicated that spiromastixones 6, 7, 12 and 14 significantly up-regulated the mRNA levels of ATP-binding cassette sub-family A1 (ABCA1) and down-regulated those of scavenger receptor CD36, while the transcription of ATP-binding cassette sub-family A1 (ABCG1) and proliferator-activated receptor gamma (PPARγ) were selectively up-regulated by 6 and 14. A transactivation reporter assay revealed that spiromastixones 6 and 14 remarkably enhanced the transcriptional activity of PPARγ. These results suggest that spiromastixones inhibit foam cell formation through upregulation of PPARγ and ABCA1/G1 and downregulation of CD36, indicating that spiromastixones 6 and 14 are promising lead compounds for further development as anti-atherogenic agents. Full article

► Show Figures

Graphical abstract

223 KiB

Open AccessReview

Marine-Based Nutraceuticals: An Innovative Trend in the Food and Supplement Industries

by Hafiz Ansar Rasul Suleria, Simone Osborne, Paul Masci and Glenda Gobe

Mar. Drugs 2015, 13(10), 6336-6351; https://doi.org/10.3390/md13106336 - 14 Oct 2015

Cited by 183 | Viewed by 17721

Abstract

Recent trends in functional foods and supplements have demonstrated that bioactive molecules play a major therapeutic role in human disease. Nutritionists and biomedical and food scientists are working together to discover new bioactive molecules that have increased potency and therapeutic benefits. Marine life [...] Read more.

Recent trends in functional foods and supplements have demonstrated that bioactive molecules play a major therapeutic role in human disease. Nutritionists and biomedical and food scientists are working together to discover new bioactive molecules that have increased potency and therapeutic benefits. Marine life constitutes almost 80% of the world biota with thousands of bioactive compounds and secondary metabolites derived from marine invertebrates such as tunicates, sponges, molluscs, bryozoans, sea slugs and many other marine organisms. These bioactive molecules and secondary metabolites possess antibiotic, antiparasitic, antiviral, anti-inflammatory, antifibrotic and anticancer activities. They are also inhibitors or activators of critical enzymes and transcription factors, competitors of transporters and sequestrants that modulate various physiological pathways. The current review summaries the widely available marine-based nutraceuticals and recent research carried out for the purposes of isolation, identification and characterization of marine-derived bioactive compounds with various therapeutic potentials. Full article

► Show Figures

Graphical abstract

840 KiB

Open AccessArticle

Cyanobacterial Toxic and Bioactive Peptides in Freshwater Bodies of Greece: Concentrations, Occurrence Patterns, and Implications for Human Health

by Spyros Gkelis, Thomas Lanaras and Kaarina Sivonen

Mar. Drugs 2015, 13(10), 6319-6335; https://doi.org/10.3390/md13106319 - 12 Oct 2015

Cited by 58 | Viewed by 8220

Abstract

Cyanobacterial harmful algal blooms represent one of the most conspicuous waterborne microbial hazards in aquatic environments mostly due to the production of toxic secondary metabolites, mainly microcystins (MCs). Other bioactive peptides are frequently found in cyanobacterial blooms, yet their concentration and ecological relevance [...] Read more.

Cyanobacterial harmful algal blooms represent one of the most conspicuous waterborne microbial hazards in aquatic environments mostly due to the production of toxic secondary metabolites, mainly microcystins (MCs). Other bioactive peptides are frequently found in cyanobacterial blooms, yet their concentration and ecological relevance is still unknown. In this paper we studied the presence and concentration of cyanobacterial peptides (microcystins, anabaenopeptins, anabaenopeptilides) in 36 Greek freshwater bodies, using HPLC-DAD, ELISA, and PP1IA. Microcystins were found in more than 90% of the samples investigated, indicating that microcystin-producing strains seem to also occur in lakes without blooms. Microcystins MC-RR, MC-LR, and MC-YR were the main toxin constituents of the bloom samples. Anabaenopeptin A and B were predominant in some samples, whereas anabaenopeptolide 90A was the only peptide found in Lake Mikri Prespa. The intracellular concentrations of anabaenopeptins produced by cyanobacterial bloom populations are determined for the first time in this study; the high (>1000 µg·L⁻¹) anabaenopeptin concentration found indicates there may be some impacts, at least on the ecology and the food web structure of the aquatic ecosystems. The maximum intracellular MC values measured in Lakes Kastoria and Pamvotis, exceeding 10,000 µg·L⁻¹, are among the highest reported. Full article

(This article belongs to the Special Issue Compounds from Cyanobacteria)

► Show Figures

Graphical abstract

652 KiB

Open AccessArticle

Six New Polyketide Decalin Compounds from Mangrove Endophytic Fungus Penicillium aurantiogriseum 328#

by Yanhong Ma, Jing Li, Meixiang Huang, Lan Liu, Jun Wang and Yongcheng Lin

Mar. Drugs 2015, 13(10), 6306-6318; https://doi.org/10.3390/md13106306 - 10 Oct 2015

Cited by 27 | Viewed by 6454

Abstract

Six new compounds with polyketide decalin ring, peaurantiogriseols A–F (1–6), along with two known compounds, aspermytin A (7), 1-propanone,3-hydroxy-1- (1,2,4a,5,6,7,8,8a-octahydro-2,5-dihydroxy-1,2,6-trimethyl-1-naphthalenyl) (8), were isolated from the fermentation products of mangrove endophytic fungus Penicillium aurantiogriseum 328#. Their [...] Read more.

Six new compounds with polyketide decalin ring, peaurantiogriseols A–F (1–6), along with two known compounds, aspermytin A (7), 1-propanone,3-hydroxy-1- (1,2,4a,5,6,7,8,8a-octahydro-2,5-dihydroxy-1,2,6-trimethyl-1-naphthalenyl) (8), were isolated from the fermentation products of mangrove endophytic fungus Penicillium aurantiogriseum 328#. Their structures were elucidated based on their structure analysis. The absolute configurations of compounds 1 and 2 were determined by ¹H NMR analysis of their Mosher esters; the absolute configurations of 3–6 were determined by using theoretical calculations of electronic circular dichroism (ECD). Compounds 1–8 showed low inhibitory activity against human aldose reductase, no activity of inducing neurite outgrowth, nor antimicrobial activity. Full article

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

► Show Figures

Graphical abstract

827 KiB

Open AccessArticle

Analysis of Mycosporine-Like Amino Acids in Selected Algae and Cyanobacteria by Hydrophilic Interaction Liquid Chromatography and a Novel MAA from the Red Alga Catenella repens

by Anja Hartmann, Kathrin Becker, Ulf Karsten, Daniel Remias and Markus Ganzera

Mar. Drugs 2015, 13(10), 6291-6305; https://doi.org/10.3390/md13106291 - 9 Oct 2015

Cited by 54 | Viewed by 10701

Abstract

Mycosporine-like amino acids (MAAs), a group of small secondary metabolites found in algae, cyanobacteria, lichens and fungi, have become ecologically and pharmacologically relevant because of their pronounced UV-absorbing and photo-protective potential. Their analytical characterization is generally achieved by reversed phase HPLC and the [...] Read more.

Mycosporine-like amino acids (MAAs), a group of small secondary metabolites found in algae, cyanobacteria, lichens and fungi, have become ecologically and pharmacologically relevant because of their pronounced UV-absorbing and photo-protective potential. Their analytical characterization is generally achieved by reversed phase HPLC and the compounds are often quantified based on molar extinction coefficients. As an alternative approach, in our study a fully validated hydrophilic interaction liquid chromatography (HILIC) method is presented. It enables the precise quantification of several analytes with adequate retention times in a single run, and can be coupled directly to MS. Excellent linear correlation coefficients (R² > 0.9991) were obtained, with limit of detection (LOD) values ranging from 0.16 to 0.43 µg/mL. Furthermore, the assay was found to be accurate (recovery rates from 89.8% to 104.1%) and precise (intra-day precision: 5.6%, inter-day precision ≤6.6%). Several algae were assayed for their content of known MAAs like porphyra-334, shinorine, and palythine. Liquid chromatography-mass spectrometry (LC-MS) data indicated a novel compound in some of them, which could be isolated from the marine species Catenella repens and structurally elucidated by nuclear magnetic resonance spectroscopy (NMR) as (E)-3-hydroxy-2-((5-hydroxy-5-(hydroxymethyl)-2-methoxy-3-((2-sulfoethyl)amino)cyclohex-2-en-1-ylidene)amino) propanoic acid, a novel MAA called catenelline. Full article

► Show Figures

Graphical abstract

1011 KiB

Open AccessArticle

Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

by Shogo Mori, Howard Williams, Davey Cagle, Kristopher Karanovich, F. David Horgen, Roger Smith III and Coran M. H. Watanabe

Mar. Drugs 2015, 13(10), 6274-6290; https://doi.org/10.3390/md13106274 - 9 Oct 2015

Cited by 13 | Viewed by 8866

Abstract

A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and [...] Read more.

A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue. Full article

► Show Figures

Graphical abstract

1668 KiB

Open AccessArticle

Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

by Junxiong Chen, Chenliang Wang, Wenjian Lan, Chunying Huang, Mengmeng Lin, Zhongyang Wang, Wanling Liang, Aikichi Iwamoto, Xiangling Yang and Huanliang Liu

Mar. Drugs 2015, 13(10), 6259-6273; https://doi.org/10.3390/md13106259 - 2 Oct 2015

Cited by 30 | Viewed by 7711

Abstract

The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX) and [...] Read more.

The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX) and some of its analogues, the secondary metabolites from marine fungus Neosartorya pseufofischeri, acted as inhibitors of the Wnt signaling pathway. In addition, we found that GTX downregulated the β-catenin levels in colorectal cancer cells with inactivating mutations of adenomatous polyposis coli (APC) or activating mutations of β-catenin. Furthermore, we demonstrated that GTX induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Together, we illustrated a practical approach to identify small-molecule inhibitors of the Wnt signaling pathway and our study indicated that GTX has therapeutic potential for the prevention or treatment of Wnt dependent cancers and other Wnt related diseases. Full article

(This article belongs to the Special Issue Marine Secondary Metabolites)

► Show Figures

Figure 1

314 KiB

Open AccessArticle

Mycemycins A–E, New Dibenzoxazepinones Isolated from Two Different Streptomycetes

by Ning Liu, Fangying Song, Fei Shang and Ying Huang

Mar. Drugs 2015, 13(10), 6247-6258; https://doi.org/10.3390/md13106247 - 30 Sep 2015

Cited by 14 | Viewed by 5983

Abstract

Five new dibenzoxazepinone derivatives, mycemycins A–E (1–5), were isolated from the ethanol extracts of mycelia of two different streptomycetes. 1 and 2 were isolated from an acidic red soil-derived strain, Streptomyces sp. FXJ1.235, and 3–5 from a [...] Read more.

Five new dibenzoxazepinone derivatives, mycemycins A–E (1–5), were isolated from the ethanol extracts of mycelia of two different streptomycetes. 1 and 2 were isolated from an acidic red soil-derived strain, Streptomyces sp. FXJ1.235, and 3–5 from a gntR gene-disrupted deep-sea strain named Streptomyces olivaceus FXJ8.012Δ1741. The structures of mycemycins were elucidated by a combination of spectroscopic analyses, including 1D- and 2D-NMR techniques. Full article

(This article belongs to the Special Issue New Approaches for Activating Silent Biogenetic Gene Clusters in Marine Microorganisms)

► Show Figures

Graphical abstract

395 KiB

Open AccessReview

Marine Carotenoids against Oxidative Stress: Effects on Human Health

by Maria Alessandra Gammone, Graziano Riccioni and Nicolantonio D'Orazio

Mar. Drugs 2015, 13(10), 6226-6246; https://doi.org/10.3390/md13106226 - 30 Sep 2015

Cited by 196 | Viewed by 12710

Abstract

Carotenoids are lipid-soluble pigments that are produced in some plants, algae, fungi, and bacterial species, which accounts for their orange and yellow hues. Carotenoids are powerful antioxidants thanks to their ability to quench singlet oxygen, to be oxidized, to be isomerized, and to [...] Read more.

Carotenoids are lipid-soluble pigments that are produced in some plants, algae, fungi, and bacterial species, which accounts for their orange and yellow hues. Carotenoids are powerful antioxidants thanks to their ability to quench singlet oxygen, to be oxidized, to be isomerized, and to scavenge free radicals, which plays a crucial role in the etiology of several diseases. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. In this respect, various novel marine carotenoids have recently been isolated from marine organisms and displayed several utilizations as nutraceuticals and pharmaceuticals. Marine carotenoids (astaxanthin, fucoxanthin, β-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. This review aims to describe the role of marine carotenoids against oxidative stress and their potential applications in preventing and treating inflammatory diseases. Full article

(This article belongs to the Special Issue Marine Carotenoids and Oxidative Stress)

► Show Figures

Figure 1

548 KiB

Open AccessCommunication

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

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

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

Cited by 53 | Viewed by 7248

Abstract

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

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

(This article belongs to the Collection Marine Polysaccharides)

► Show Figures

Figure 1

653 KiB

Open AccessReview

Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

by Elena Talero, Sofía García-Mauriño, Javier Ávila-Román, Azahara Rodríguez-Luna, Antonio Alcaide and Virginia Motilva

Mar. Drugs 2015, 13(10), 6152-6209; https://doi.org/10.3390/md13106152 - 30 Sep 2015

Cited by 185 | Viewed by 16604

Abstract

The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress [...] Read more.

The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins). This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity. Full article

► Show Figures

Graphical abstract

883 KiB

Open AccessArticle

Photo-Oxidative Stress-Driven Mutagenesis and Adaptive Evolution on the Marine Diatom Phaeodactylum tricornutum for Enhanced Carotenoid Accumulation

by Zhiqian Yi, Maonian Xu, Manuela Magnusdottir, Yuetuan Zhang, Sigurdur Brynjolfsson and Weiqi Fu

Mar. Drugs 2015, 13(10), 6138-6151; https://doi.org/10.3390/md13106138 - 29 Sep 2015

Cited by 69 | Viewed by 9630

Abstract

Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve [...] Read more.

Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE) was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS) was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress. Full article

(This article belongs to the Special Issue Marine Carotenoids and Oxidative Stress)

► Show Figures

Graphical abstract

907 KiB

Open AccessArticle

Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass

by Tatiana G. Polotow, Sandra C. Poppe, Cristina V. Vardaris, Douglas Ganini, Maísa Guariroba, Rita Mattei, Elaine Hatanaka, Maria F. Martins, Eduardo F. Bondan and Marcelo P. Barros

Mar. Drugs 2015, 13(10), 6117-6137; https://doi.org/10.3390/md13106117 - 28 Sep 2015

Cited by 24 | Viewed by 8495

Abstract

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial [...] Read more.

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

► Show Figures

Figure 1

685 KiB

Open AccessArticle

Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells

by Ming-De Yan, Chih-Jung Yao, Jyh-Ming Chow, Chia-Lun Chang, Pai-An Hwang, Shuang-En Chuang, Jacqueline Whang-Peng and Gi-Ming Lai

Mar. Drugs 2015, 13(10), 6099-6116; https://doi.org/10.3390/md13106099 - 24 Sep 2015

Cited by 98 | Viewed by 9602

Abstract

Accumulating evidence has revealed that fucoidan exhibits anti-tumor activities by arresting cell cycle and inducing apoptosis in many types of cancer cells including hepatocellular carcinoma (HCC). Exploring its effect on microRNA expression, we found that fucoidan markedly upregulated miR-29b of human HCC cells. [...] Read more.

Accumulating evidence has revealed that fucoidan exhibits anti-tumor activities by arresting cell cycle and inducing apoptosis in many types of cancer cells including hepatocellular carcinoma (HCC). Exploring its effect on microRNA expression, we found that fucoidan markedly upregulated miR-29b of human HCC cells. The induction of miR-29b was accompanied with suppression of its downstream target DNMT3B in a dose-dependent manner. The reduction of luciferase activity of DNMT3B 3′-UTR reporter by fucoidan was as markedly as that by miR-29b mimic, indicating that fucoidan induced miR-29b to suppress DNMT3B. Accordingly, the mRNA and protein levels of MTSS1 (metastasis suppressor 1), a target silenced by DNMT3B, were increased after fucoidan treatment. Furthermore, fucoidan also down-regulated TGF-β receptor and Smad signaling of HCC cells. All these effects leaded to the inhibition of EMT (increased E-cadherin and decreased N-cadherin) and prevention of extracellular matrix degradation (increased TIMP-1 and decreased MMP2, 9), by which the invasion activity of HCC cells was diminished. Our results demonstrate the profound effect of fucoidan not only on the regulation of miR-29b-DNMT3B-MTSS1 axis but also on the inhibition of TGF-β signaling in HCC cells, suggesting the potential of using fucoidan as integrative therapeutics against invasion and metastasis of HCC. Full article

► Show Figures

Graphical abstract

2390 KiB

Open AccessArticle

Investigation of Interspecies Interactions within Marine Micromonosporaceae Using an Improved Co-Culture Approach

by Navid Adnani, Emmanuel Vazquez-Rivera, Srikar N. Adibhatla, Gregory A. Ellis, Doug R. Braun and Tim S. Bugni

Mar. Drugs 2015, 13(10), 6082-6098; https://doi.org/10.3390/md13106082 - 24 Sep 2015

Cited by 31 | Viewed by 8018

Abstract

With respect to bacterial natural products, a significant outcome of the genomic era was that the biosynthetic potential in many microorganisms surpassed the number of compounds isolated under standard laboratory growth conditions, particularly among certain members in the phylum Actinobacteria. Our group, as [...] Read more.

With respect to bacterial natural products, a significant outcome of the genomic era was that the biosynthetic potential in many microorganisms surpassed the number of compounds isolated under standard laboratory growth conditions, particularly among certain members in the phylum Actinobacteria. Our group, as well as others, investigated interspecies interactions, via co-culture, as a technique to coax bacteria to produce novel natural products. While co-culture provides new opportunities, challenges exist and questions surrounding these methods remain unanswered. In marine bacteria, for example, how prevalent are interspecies interactions and how commonly do interactions result in novel natural products? In an attempt to begin to answer basic questions surrounding co-culture of marine microorganisms, we have tested both antibiotic activity-based and LC/MS-based methods to evaluate Micromonosporaceae secondary metabolite production in co-culture. Overall, our investigation of 65 Micromonosporaceae led to the identification of 12 Micromonosporaceae across three genera that produced unique metabolites in co-culture. Our results suggest that interspecies interactions were prevalent between marine Micromonosporaceae and marine mycolic acid-containing bacteria. Furthermore, our approach highlights a sensitive and rapid method for investigating interspecies interactions in search of novel antibiotics, secondary metabolites, and genes. Full article

► Show Figures

Graphical abstract

3018 KiB

Open AccessArticle

Astaxanthin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cells via Inhibition of Nf-Κb P65 and Wnt/Β-Catenin in Vitro

by Jingjing Li, Weiqi Dai, Yujing Xia, Kan Chen, Sainan Li, Tong Liu, Rong Zhang, Jianrong Wang, Wenxia Lu, Yuqing Zhou, Qin Yin, Huerxidan Abudumijiti, Rongxia Chen, Yuanyuan Zheng, Fan Wang, Jie Lu, Yingqun Zhou and Chuanyong Guo

Mar. Drugs 2015, 13(10), 6064-6081; https://doi.org/10.3390/md13106064 - 24 Sep 2015

Cited by 67 | Viewed by 8903

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor that can cause systemic invasion; however, the exact etiology and molecular mechanism are unknown. Astaxanthin (ASX), a powerful antioxidant, has efficient anti-oxidant, anti-inflammatory, and other activities, and has great research prospects in cancer therapy. We selected [...] Read more.

Hepatocellular carcinoma (HCC) is a malignant tumor that can cause systemic invasion; however, the exact etiology and molecular mechanism are unknown. Astaxanthin (ASX), a powerful antioxidant, has efficient anti-oxidant, anti-inflammatory, and other activities, and has great research prospects in cancer therapy. We selected the human hepatoma cell lines, LM3 and SMMC-7721, to study the anti-tumor effect and related mechanisms of ASX. The cell lines were treated with different concentrations of ASX, and its solvent DMSO as a control, for different time periods and the results were determined using CCK8, qRT-PCR, WB, apoptotic staining, and flow cytometry. ASX induced significant apoptosis of HCC cells, and its effect may have been caused by NF-κB p65 and Wnt/β-catenin down-regulation via negative activation of PI3K/Akt and ERK. Antitumor research on ASX has provided us with a potential therapy for patients with hepatomas. Full article

► Show Figures

Graphical abstract

1952 KiB

Open AccessArticle

New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa

by Irina Gladkikh, Margarita Monastyrnaya, Elena Zelepuga, Oksana Sintsova, Valentin Tabakmakher, Oksana Gnedenko, Alexis Ivanov, Kuo-Feng Hua and Emma Kozlovskaya

Mar. Drugs 2015, 13(10), 6038-6063; https://doi.org/10.3390/md13106038 - 24 Sep 2015

Cited by 25 | Viewed by 6233

Abstract

Sea anemones are a rich source of Kunitz-type polypeptides that possess not only protease inhibitor activity, but also Kv channels toxicity, analgesic, antihistamine, and anti-inflammatory activities. Two Kunitz-type inhibitors belonging to a new Heteractis crispa RG (HCRG) polypeptide subfamily have been isolated from [...] Read more.

Sea anemones are a rich source of Kunitz-type polypeptides that possess not only protease inhibitor activity, but also Kv channels toxicity, analgesic, antihistamine, and anti-inflammatory activities. Two Kunitz-type inhibitors belonging to a new Heteractis crispa RG (HCRG) polypeptide subfamily have been isolated from the sea anemone Heteractis crispa. The amino acid sequences of HCRG1 and HCRG2 identified using the Edman degradation method share up to 95% of their identity with the representatives of the HCGS polypeptide multigene subfamily derived from H. crispa cDNA. Polypeptides are characterized by positively charged Arg at the N-terminus as well as P1 Lys residue at their canonical binding loop, identical to those of bovine pancreatic trypsin inhibitor (BPTI). These polypeptides are shown by our current evidence to be more potent inhibitors of trypsin than the known representatives of the HCGS subfamily with P1Thr. The kinetic and thermodynamic characteristics of the intermolecular interactions between inhibitors and serine proteases were determined by the surface plasmon resonance (SPR) method. Residues functionally important for polypeptide binding to trypsin were revealed using molecular modeling methods. Furthermore, HCRG1 and HCRG2 possess anti-inflammatory activity, reducing tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) secretions, as well as proIL-1β expression in lipopolysaccharide (LPS)-activated macrophages. However, there was no effect on nitric oxide (NO) generation. Full article

► Show Figures

Graphical abstract

339 KiB

Open AccessArticle

Ocean Warming and CO₂-Induced Acidification Impact the Lipid Content of a Marine Predatory Gastropod

by Roselyn Valles-Regino, Rick Tate, Brendan Kelaher, Dale Savins, Ashley Dowell and Kirsten Benkendorff

Mar. Drugs 2015, 13(10), 6019-6037; https://doi.org/10.3390/md13106019 - 24 Sep 2015

Cited by 53 | Viewed by 9057

Abstract

Ocean warming and acidification are current global environmental challenges impacting aquatic organisms. A shift in conditions outside the optimal environmental range for marine species is likely to generate stress that could impact metabolic activity, with consequences for the biosynthesis of marine lipids. The [...] Read more.

Ocean warming and acidification are current global environmental challenges impacting aquatic organisms. A shift in conditions outside the optimal environmental range for marine species is likely to generate stress that could impact metabolic activity, with consequences for the biosynthesis of marine lipids. The aim of this study was to investigate differences in the lipid content of Dicathais orbita exposed to current and predicted future climate change scenarios. The whelks were exposed to a combination of temperature and CO₂-induced acidification treatments in controlled flowthrough seawater mesocosms for 35 days. Under current conditions, D. orbita foot tissue has an average of 6 mg lipid/g tissue, but at predicted future ocean temperatures, the total lipid content dropped significantly, to almost half. The fatty acid composition is dominated by polyunsaturated fatty acids (PUFA 52%) with an n-3:6 fatty acid ratio of almost 2, which remains unchanged under future ocean conditions. However, we detected an interactive effect of temperature and pCO₂ on the % PUFAs and n-3 and n-6 fatty acids were significantly reduced by elevated water temperature, while both the saturated and monounsaturated fatty acids were significantly reduced under increased pCO₂ acidifying conditions. The present study indicates the potential for relatively small predicted changes in ocean conditions to reduce lipid reserves and alter the fatty acid composition of a predatory marine mollusc. This has potential implications for the growth and survivorship of whelks under future conditions, but only minimal implications for human consumption of D. orbita as nutritional seafood are predicted. Full article

(This article belongs to the Special Issue Marine Lipids)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Mar. Drugs, Volume 13, Issue 10 (October 2015) – 29 articles , Pages 6019-6549

Further Information

Guidelines

MDPI Initiatives

Follow MDPI