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Mar. Drugs, Volume 17, Issue 2 (February 2019)

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Cover Story (view full-size image) Marine sponges of the genus Suberea (family Aplysinellidae) are recognized as producers of [...] Read more.
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Open AccessArticle Functional Characterization of OXYL, A SghC1qDC LacNAc-specific Lectin from The Crinoid Feather Star Anneissia Japonica
Mar. Drugs 2019, 17(2), 136; https://doi.org/10.3390/md17020136
Received: 29 January 2019 / Revised: 14 February 2019 / Accepted: 18 February 2019 / Published: 25 February 2019
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Abstract
We identified a lectin (carbohydrate-binding protein) belonging to the complement 1q(C1q) family in the feather star Anneissia japonica (a crinoid pertaining to the phylum Echinodermata). The combination of Edman degradation and bioinformatics sequence analysis characterized the primary structure of this novel lectin, named [...] Read more.
We identified a lectin (carbohydrate-binding protein) belonging to the complement 1q(C1q) family in the feather star Anneissia japonica (a crinoid pertaining to the phylum Echinodermata). The combination of Edman degradation and bioinformatics sequence analysis characterized the primary structure of this novel lectin, named OXYL, as a secreted 158 amino acid-long globular head (sgh)C1q domain containing (C1qDC) protein. Comparative genomics analyses revealed that OXYL pertains to a family of intronless genes found with several paralogous copies in different crinoid species. Immunohistochemistry assays identified the tissues surrounding coelomic cavities and the arms as the main sites of production of OXYL. Glycan array confirmed that this lectin could quantitatively bind to type-2 N-acetyllactosamine (LacNAc: Galβ1-4GlcNAc), but not to type-1 LacNAc (Galβ1-3GlcNAc). Although OXYL displayed agglutinating activity towards Pseudomonas aeruginosa, it had no effect on bacterial growth. On the other hand, it showed a significant anti-biofilm activity. We provide evidence that OXYL can adhere to the surface of human cancer cell lines BT-474, MCF-7, and T47D, with no cytotoxic effect. In BT-474 cells, OXYL led to a moderate activation of the p38 kinase in the MAPK signaling pathway, without affecting the activity of caspase-3. Bacterial agglutination, anti-biofilm activity, cell adhesion, and p38 activation were all suppressed by co-presence of LacNAc. This is the first report on a type-2 LacNAc-specific lectin characterized by a C1q structural fold. Full article
(This article belongs to the Special Issue Marine Glycoconjugates: Trends and Perspectives)
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Open AccessArticle Amino Acid Composition, Antioxidant, and Cytoprotective Effect of Blue Mussel (Mytilus edulis) Hydrolysate through the Inhibition of Caspase-3 Activation in Oxidative Stress-Mediated Endothelial Cell Injury
Mar. Drugs 2019, 17(2), 135; https://doi.org/10.3390/md17020135
Received: 30 January 2019 / Revised: 16 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
Enhanced oxidative stress plays a central role in promoting endothelial dysfunction, leading to the development of atherosclerosis. In this study, we investigated the protective effects of the hydrolysates derived from blue mussel (Mytilus edulis) against H2O2-mediated oxidative [...] Read more.
Enhanced oxidative stress plays a central role in promoting endothelial dysfunction, leading to the development of atherosclerosis. In this study, we investigated the protective effects of the hydrolysates derived from blue mussel (Mytilus edulis) against H2O2-mediated oxidative injury in human umbilical vein endothelial cells (HUVECs). The blue mussel hydrolysates were prepared by enzymatic hydrolysis with eight proteases, and blue mussel-α-chymotrypsin hydrolysate (BMCH) showed the highest antioxidant activities in DPPH radical scavenging, ABTS+ radical scavenging, and ORAC value compared to those of the other hydrolysates. BMCH also inhibited Cu2+-mediated low density lipoprotein (LDL) oxidation. Treatment of H2O2 resulted in the decreased HUVEC viability whereas pre-treatment with BMCH increased HUVEC viability and reduced reactive oxygen species (ROS) generation. BMCH pre-treatment increased cellular antioxidant capacities, including levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) against H2O2-mediated oxidative stress in HUVECs. Flow cytometry and western blot analysis revealed that BMCH pre-treatment significantly reduced H2O2-mediated HUVEC apoptosis through inhibition of caspase-3 activation. Real-time-qPCR analysis showed that BMCH down-regulated expression of p53 and caspase-3 genes, as well as decreased the bax/bcl-2 ratio. Taken together, these results indicate that BMCH may be useful as functional food ingredients for protecting endothelial dysfunction or related disease. Full article
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Open AccessArticle Barrel Jellyfish (Rhizostoma pulmo) as Source of Antioxidant Peptides
Mar. Drugs 2019, 17(2), 134; https://doi.org/10.3390/md17020134
Received: 31 January 2019 / Revised: 15 February 2019 / Accepted: 19 February 2019 / Published: 23 February 2019
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Abstract
The jellyfish Rhizostoma pulmo, Macrì 1778 (Cnidaria, Rhizostomae) undergoes recurrent outbreaks in the Mediterranean coastal waters, with large biomass populations representing a nuisance or damage for marine and maritime activities. A preliminary overview of the antioxidant activity (AA) of R. pulmo proteinaceous [...] Read more.
The jellyfish Rhizostoma pulmo, Macrì 1778 (Cnidaria, Rhizostomae) undergoes recurrent outbreaks in the Mediterranean coastal waters, with large biomass populations representing a nuisance or damage for marine and maritime activities. A preliminary overview of the antioxidant activity (AA) of R. pulmo proteinaceous compounds is provided here based on the extraction and characterization of both soluble and insoluble membrane-fractioned proteins, the latter digested by sequential enzymatic hydrolyses with pepsin and collagenases. All jellyfish proteins showed significant AA, with low molecular weight (MW) proteins correlated with greater antioxidant activity. In particular, collagenase-hydrolysed collagen resulted in peptides with MW lower than 3 kDa, ranging 3–10 kDa or 10–30 kDa, with AA inversely proportional to MW. No cytotoxic effect was detected on cultured human keratinocytes (HEKa) in a range of protein concentration 0.05–20 μg/mL for all tested protein fractions except for soluble proteins higher than 30 kDa, likely containing the jellyfish venom compounds. Furthermore, hydrolyzed jellyfish collagen peptides showed a significantly higher AA and provided a greater protective effect against oxidative stress in HEKa than the hydrolyzed collagen peptides from vertebrates. Due to a high reproductive potential, jellyfish may represent a potential socioeconomic opportunity as a source of natural bioactive compounds, with far-reaching beneficial implications. Eventually, improvements in processing technology will promote the use of untapped marine biomasses in nutraceutical, cosmeceutical, and pharmaceutical fields, turning marine management problems into a more positive perspective. Full article
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Open AccessArticle 2-Alkyl-4-hydroxyquinolines from a Marine-Derived Streptomyces sp. Inhibit Hyphal Growth Induction in Candida albicans
Mar. Drugs 2019, 17(2), 133; https://doi.org/10.3390/md17020133
Received: 2 February 2019 / Revised: 18 February 2019 / Accepted: 20 February 2019 / Published: 22 February 2019
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Abstract
Four 2-alkyl-4-hydroxyquinoline derivatives (14) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with [...] Read more.
Four 2-alkyl-4-hydroxyquinoline derivatives (14) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds 1 and 2 exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound 1 acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus Candida albicans, with an IC50 value of 11.4 μg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound 1 inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of HWP1 and ALS3 mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound 1. These results indicate that compound 1 acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in Candida albicans. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes - II)
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Open AccessArticle Eicosapentaenoic Acid Extraction from Nannochloropsis gaditana Using Carbon Dioxide at Supercritical Conditions
Mar. Drugs 2019, 17(2), 132; https://doi.org/10.3390/md17020132
Received: 20 December 2018 / Revised: 19 February 2019 / Accepted: 20 February 2019 / Published: 22 February 2019
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Abstract
This research shows that carbon dioxide supercritical fluid (CO2-SF) is an emerging technology for the extraction of high interest compounds for applications in the manufacturing of pharmaceuticals, nutraceuticals, and cosmetics from microalgae. The purpose of this study is to recover fatty [...] Read more.
This research shows that carbon dioxide supercritical fluid (CO2-SF) is an emerging technology for the extraction of high interest compounds for applications in the manufacturing of pharmaceuticals, nutraceuticals, and cosmetics from microalgae. The purpose of this study is to recover fatty acids (FAs) and, more precisely, eicosapentaenoic acid (EPA) from Nannochloropsis gaditana biomass by CO2-SF extraction. In the paper, the effect of mechanical pre-treatment was evaluated with the aim of increasing FAs recovery. Extraction was performed at a pressure range of 250–550 bars and a CO2 flow rate of 7.24 and 14.48 g/min, while temperature was fixed at 50 or 65 °C. The effect of these parameters on the extraction yield was assessed at each extraction cycle, 20 min each, for a total extraction time of 100 min. Furthermore, the effect of biomass loading on EPA recovery was evaluated. The highest EPA extraction yield, i.e., 11.50 mg/g, corresponding to 27.4% EPA recovery, was obtained at 65 °C and 250 bars with a CO2 flow rate of 7.24 g/min and 1.0 g biomass loading. The increased CO2 flow rate from 7.24 to 14.48 g/min enhanced the cumulative EPA recovery at 250 bars. The purity of EPA could be improved by biomass loading of 2.01 g, even if recovery was reduced. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Open AccessArticle Express Method for Isolation of Ready-to-Use 3D Chitin Scaffolds from Aplysina archeri (Aplysineidae: Verongiida) Demosponge
Mar. Drugs 2019, 17(2), 131; https://doi.org/10.3390/md17020131
Received: 26 January 2019 / Revised: 16 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
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Abstract
Sponges are a valuable source of natural compounds and biomaterials for many biotechnological applications. Marine sponges belonging to the order Verongiida are known to contain both chitin and biologically active bromotyrosines. Aplysina archeri (Aplysineidae: Verongiida) is well known to contain bromotyrosines with relevant [...] Read more.
Sponges are a valuable source of natural compounds and biomaterials for many biotechnological applications. Marine sponges belonging to the order Verongiida are known to contain both chitin and biologically active bromotyrosines. Aplysina archeri (Aplysineidae: Verongiida) is well known to contain bromotyrosines with relevant bioactivity against human and animal diseases. The aim of this study was to develop an express method for the production of naturally prefabricated 3D chitin and bromotyrosine-containing extracts simultaneously. This new method is based on microwave irradiation (MWI) together with stepwise treatment using 1% sodium hydroxide, 20% acetic acid, and 30% hydrogen peroxide. This approach, which takes up to 1 h, made it possible to isolate chitin from the tube-like skeleton of A. archeri and to demonstrate the presence of this biopolymer in this sponge for the first time. Additionally, this procedure does not deacetylate chitin to chitosan and enables the recovery of ready-to-use 3D chitin scaffolds without destruction of the unique tube-like fibrous interconnected structure of the isolated biomaterial. Furthermore, these mechanically stressed fibers still have the capacity for saturation with water, methylene blue dye, crude oil, and blood, which is necessary for the application of such renewable 3D chitinous centimeter-sized scaffolds in diverse technological and biomedical fields. Full article
(This article belongs to the Special Issue Marine Chitin 2019)
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Open AccessArticle Wound Healing Potential of Spirulina Protein on CCD-986sk Cells
Mar. Drugs 2019, 17(2), 130; https://doi.org/10.3390/md17020130
Received: 17 January 2019 / Revised: 13 February 2019 / Accepted: 20 February 2019 / Published: 22 February 2019
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Abstract
Wound healing is a dynamic and complex process. The proliferation and migration of dermal fibroblasts are crucial for wound healing. Recent studies have indicated that the extracts from Spirulina platensis have a positive potential for wound healing. However, its underlying mechanism is not [...] Read more.
Wound healing is a dynamic and complex process. The proliferation and migration of dermal fibroblasts are crucial for wound healing. Recent studies have indicated that the extracts from Spirulina platensis have a positive potential for wound healing. However, its underlying mechanism is not fully understood. Our previous study showed that spirulina crude protein (SPCP) promoted the viability of human dermal fibroblast cell line (CCD-986sk cells). In this study, we further investigated the wound healing effect and corresponding mechanisms of SPCP on CCD-986sk cells. Bromodeoxyuridine (BrdU) assay showed that SPCP promoted the proliferation of CCD-986sk cells. The wound healing assay showed that SPCP promoted the migration of CCD-986sk cells. Furthermore, cell cycle analysis demonstrated that SPCP promoted CCD-986sk cells to enter S and G2/M phases from G0/G1 phase. Western blot results showed that SPCP significantly upregulated the expression of cyclin D1, cyclin E, cyclin-dependent kinase 2 (Cdk2), cyclin-dependent kinase 4 (Cdk4), and cyclin-dependent kinase 6 (Cdk6), as well as inhibited the expression of CDK inhibitors p21 and p27 in CCD-986sk cells. In the meanwhile, SPCP promoted the phosphorylation and activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). However, the phosphorylation of Akt was significantly blocked by PI3K inhibitor (LY294002), which in turn reduced the SPCP-induced proliferation and migration of CCD-986sk cells. Therefore, the results presenting in this study suggested that SPCP can promote the proliferation and migration of CCD-986sk cells; the PI3K/Akt signaling pathway play a positive and important role in these processes. Full article
(This article belongs to the Special Issue The Pharmacological Potential of Marine-Derived Peptides and Proteins)
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Open AccessArticle Anti-Inflammatory Activity of β-thymosin Peptide Derived from Pacific Oyster (Crassostrea gigas) on NO and PGE2 Production by Down-Regulating NF-κB in LPS-Induced RAW264.7 Macrophage Cells
Mar. Drugs 2019, 17(2), 129; https://doi.org/10.3390/md17020129
Received: 21 December 2018 / Revised: 4 February 2019 / Accepted: 18 February 2019 / Published: 21 February 2019
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Abstract
β-thymosin is known for having 43 amino acids, being water-soluble, having a light molecular weight and ubiquitous polypeptide. The biological activities of β-thymosin are diverse and include the promotion of wound healing, reduction of inflammation, differentiation of T cells and inhibition of apoptosis. [...] Read more.
β-thymosin is known for having 43 amino acids, being water-soluble, having a light molecular weight and ubiquitous polypeptide. The biological activities of β-thymosin are diverse and include the promotion of wound healing, reduction of inflammation, differentiation of T cells and inhibition of apoptosis. Our previous studies showed that oyster β-thymosin originated from the mantle of the Pacific oyster, Crassostrea gigas and had antimicrobial activity. In this study, we investigated the anti-inflammatory effects of oyster β-thymosin in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells using human β-thymosin as a control. Oyster β-thymosin inhibited the nitric oxide (NO) production as much as human β-thymosin in LPS-induced RAW264.7 cells. It also showed that oyster β-thymosin suppressed the expression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, oyster β-thymosin reduced inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Oyster β-thymosin also suppressed the nuclear translocation of phosphorylated nuclear factor-κB (NF-κB) and degradation of inhibitory κB (IκB) in LPS-induced RAW264.7 cells. These results suggest that oyster β-thymosin, which is derived from the mantle of the Pacific oyster, has as much anti-inflammatory effects as human β-thymosin. Additionally, oyster β-thymosin suppressed NO production, PGE2 production and inflammatory cytokines expression via NF-κB in LPS-induced RAW264.7 cells. Full article
(This article belongs to the Special Issue The Pharmacological Potential of Marine-Derived Peptides and Proteins)
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Open AccessArticle Heterologous Expression of the Marine-Derived Quorum Quenching Enzyme MomL Can Expand the Antibacterial Spectrum of Bacillus brevis
Mar. Drugs 2019, 17(2), 128; https://doi.org/10.3390/md17020128
Received: 25 January 2019 / Revised: 14 February 2019 / Accepted: 18 February 2019 / Published: 21 February 2019
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Abstract
Quorum sensing (QS) is closely associated with the production of multiple virulence factors in bacterial pathogens. N-acyl homoserine lactones (AHLs) are important QS signal molecules that modulate the virulence of gram-negative pathogenic bacteria. Enzymatic degradation of AHLs to interrupt QS, termed quorum [...] Read more.
Quorum sensing (QS) is closely associated with the production of multiple virulence factors in bacterial pathogens. N-acyl homoserine lactones (AHLs) are important QS signal molecules that modulate the virulence of gram-negative pathogenic bacteria. Enzymatic degradation of AHLs to interrupt QS, termed quorum quenching (QQ), has been considered a novel strategy for reduction of pathogenicity and prevention of bacterial disease. However, the low expression levels of QQ proteins in the original host bacteria has affected the applications of these proteins. Previously, we identified a novel marine QQ enzyme, named MomL, with high activity and promising biocontrol function. In this study, we linked the target fragment momL to pNCMO2, which provided a basis for the first heterologous expression of MomL in the antifungal and anti-gram-positive-bacteria biocontrol strain Bacillus brevis, and obtaining the recombinant strain named BbMomL. The QQ activity of BbMomL was confirmed using a series of bioassays. BbMomL could not only degrade the exogenous signal molecule C6-HSL, but also the AHL signal molecules produced by the gram-negative pathogens Pectobacterium carotovorum subsp. carotovorum (Pcc) and Pseudomonas aeruginosa PAO1. In addition, BbMomL significantly reduced the secretion of pathogenic factors and the pathogenicity of Pcc and P. aeruginosa PAO1. We tested the biocontrol function of BbMomL for prevention of plant diseases in vitro. The result indicates that BbMomL has a broad antibacterial spectrum. Compared with wild-type B. brevis, BbMomL not only inhibited fungi and gram-positive bacterial pathogens but also considerably inhibited gram-negative bacterial pathogens. Moreover, the Bacillus brevis expression system has good application prospects and is an ideal host for expression and secretion of foreign proteins. Full article
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Open AccessArticle Identification of the Anti-Infective Aborycin Biosynthetic Gene Cluster from Deep-Sea-Derived Streptomyces sp. SCSIO ZS0098 Enables Production in a Heterologous Host
Mar. Drugs 2019, 17(2), 127; https://doi.org/10.3390/md17020127
Received: 1 February 2019 / Revised: 15 February 2019 / Accepted: 17 February 2019 / Published: 21 February 2019
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Abstract
Aborycin is a ribosomally synthesized member of the type I lasso peptide natural products. In the present study, aborycin was isolated and identified from the deep-sea-derived microbe Streptomyces sp. SCSIO ZS0098. The aborycin biosynthetic gene cluster (abo) was identified on the [...] Read more.
Aborycin is a ribosomally synthesized member of the type I lasso peptide natural products. In the present study, aborycin was isolated and identified from the deep-sea-derived microbe Streptomyces sp. SCSIO ZS0098. The aborycin biosynthetic gene cluster (abo) was identified on the basis of genome sequence analyses and then heterologously expressed in Streptomyces coelicolor M1152 to effectively produce aborycin. Aborycin generated in this fashion exhibited moderate antibacterial activity against 13 Staphylococcus aureus strains from various sources with minimum inhibitory concentrations MICs = 8.0~128 µg/mL, against Enterococcus faecalis ATCC 29212 with an MIC = 8.0 µg/mL, and against Bacillus thuringiensis with MIC = 2.0 µg/mL. Additionally, aborycin displayed potent antibacterial activity (MIC = 0.5 µg/mL) against the poultry pathogen Enterococcus gallinarum 5F52C. The reported abo cluster clearly has the potential to provide a means of expanding the repertoire of anti-infective type I lasso peptides. Full article
(This article belongs to the Special Issue Deep-Sea Natural Products II)
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Open AccessArticle Anticancer Activity of Gukulenin A Isolated from the Marine Sponge Phorbas gukhulensis In Vitro and In Vivo
Mar. Drugs 2019, 17(2), 126; https://doi.org/10.3390/md17020126
Received: 11 January 2019 / Revised: 16 February 2019 / Accepted: 18 February 2019 / Published: 21 February 2019
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Gukulenin A is a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. In this study, we examined the anticancer activities of gukulenin A in ovarian cancer cell lines (A2780, SKOV3, OVCAR-3, and TOV-21G) and in an ovarian cancer mouse model generated [...] Read more.
Gukulenin A is a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. In this study, we examined the anticancer activities of gukulenin A in ovarian cancer cell lines (A2780, SKOV3, OVCAR-3, and TOV-21G) and in an ovarian cancer mouse model generated by injecting A2780 cells. We found that gukulenin A suppressed tumor growth in A2780-bearing mice. Gukulenin A markedly inhibited cell viability in four ovarian cancer cell lines, including the A2780 cell line. Gukulenin A treatment increased the fraction of cells accumulated at the sub G1 phase in a dose-dependent manner and the population of annexin V-positive cells, suggesting that gukulenin A induces apoptotic cell death in ovarian cancer cells. In addition, gukulenin A triggered the activation of caspase-3, -8, and -9, and caspase inhibitors attenuated gukulenin A-induced A2780 cell death. The results suggest that gukulenin A may be a potential therapeutic agent for ovarian cancer. Full article
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Open AccessArticle Fusarisolins A–E, Polyketides from the Marine-Derived Fungus Fusarium solani H918
Mar. Drugs 2019, 17(2), 125; https://doi.org/10.3390/md17020125
Received: 31 January 2019 / Revised: 14 February 2019 / Accepted: 15 February 2019 / Published: 20 February 2019
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Five new (fusarisolins A–E, 1 to 5) and three known (6 to 8) polyketides were isolated from the marine-derived fungus Fusarium solani H918, along with six known phenolics (9 to 14). Their structures were established by comprehensive spectroscopic [...] Read more.
Five new (fusarisolins A–E, 1 to 5) and three known (6 to 8) polyketides were isolated from the marine-derived fungus Fusarium solani H918, along with six known phenolics (9 to 14). Their structures were established by comprehensive spectroscopic data analyses, methoxyphenylacetic acid (MPA) method, chemical conversion, and by comparison with data reported in the literature. Compounds 1 and 2 are the first two naturally occurring 21 carbons polyketides featuring a rare β- and γ-lactone unit, respectively. All isolates (1 to 14) were evaluated for their inhibitory effects against tea pathogenic fungus Pestalotiopsis theae and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase gene expression. Compound 8 showed potent antifungal activity with an ED50 value of 55 μM, while 1, 8, 13, and 14 significantly inhibited HMG-CoA synthase gene expression. Full article
(This article belongs to the Special Issue Marine-Derived Polyketides with Antibiotic Activity)
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Open AccessArticle Growth and Biochemical Composition of Porphyridium purpureum SCS-02 under Different Nitrogen Concentrations
Mar. Drugs 2019, 17(2), 124; https://doi.org/10.3390/md17020124
Received: 18 January 2019 / Revised: 16 February 2019 / Accepted: 18 February 2019 / Published: 20 February 2019
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Abstract
Microalgae of the genus Porphyridium show great potential for large-scale commercial cultivation, as they accumulate large quantities of B-phycoerythrin (B-PE), long chain polyunsaturated fatty acids (LC-PUFAs) and exopolysaccharide (EPS). The present study aimed to adjust culture nitrogen concentrations to produce Porphyridium biomass rich [...] Read more.
Microalgae of the genus Porphyridium show great potential for large-scale commercial cultivation, as they accumulate large quantities of B-phycoerythrin (B-PE), long chain polyunsaturated fatty acids (LC-PUFAs) and exopolysaccharide (EPS). The present study aimed to adjust culture nitrogen concentrations to produce Porphyridium biomass rich in B-PE, LC-PUFAs and EPS. Porphyridium purpureum SCS-02 was cultured in ASW culture medium with low nitrogen supply (LN, 3.5 mM), medium nitrogen supply (MN, 5.9 mM) or high nitrogen supply (HN, 17.6 mM). HN significantly enhanced the accumulation of biomass, intracellular protein, B-PE and eicosapentaenoic acid. LN increased the intracellular carbohydrate and arachidonic acid content, and promoted the secretion of EPS. The total lipids content was almost unaffected by nitrogen concentration. Based on these results, a semi-continuous two-step process was proposed, which included the production of biomass rich in B-PE and LC-PUFAs with sufficient nitrogen, and induced EPS excretion with limited nitrogen and strong light. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Open AccessArticle Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway
Mar. Drugs 2019, 17(2), 123; https://doi.org/10.3390/md17020123
Received: 12 January 2019 / Revised: 10 February 2019 / Accepted: 14 February 2019 / Published: 18 February 2019
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Abstract
Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide [...] Read more.
Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ1–42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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Open AccessArticle Anti-Proliferation Activity of a Decapeptide from Perinereies aibuhitensis toward Human Lung Cancer H1299 Cells
Mar. Drugs 2019, 17(2), 122; https://doi.org/10.3390/md17020122
Received: 1 February 2019 / Revised: 11 February 2019 / Accepted: 15 February 2019 / Published: 18 February 2019
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Abstract
Perinereis aibuhitensis peptide (PAP) is a decapeptide (Ile-Glu-Pro-Gly-Thr-Val-Gly-Met-Met-Phe, IEPGTVGMMF) with anticancer activity that was purified from an enzymatic hydrolysate of Perinereis aibuhitensis. In the present study, the anticancer effect of PAP on H1299 cell proliferation was investigated. Our results showed that PAP [...] Read more.
Perinereis aibuhitensis peptide (PAP) is a decapeptide (Ile-Glu-Pro-Gly-Thr-Val-Gly-Met-Met-Phe, IEPGTVGMMF) with anticancer activity that was purified from an enzymatic hydrolysate of Perinereis aibuhitensis. In the present study, the anticancer effect of PAP on H1299 cell proliferation was investigated. Our results showed that PAP promoted apoptosis and inhibited the proliferation of H1299 cells in a time- and dose-dependent manner. When the PAP concentration reached 0.92 mM, more than 95% of treated cells died after 72 h of treatment. Changes in cell morphology were further analyzed using an inverted microscope and AO/EB staining and flow cytometry was adopted for detecting apoptosis and cell cycle phase. The results showed that the early and late apoptosis rates of H1299 cells increased significantly after treatment with PAP and the total apoptosis rate was significantly higher than that of the control group. Moreover, after treatment with PAP, the number of cells in the S phase of cells was significantly reduced and the ability for the cells to proliferate was also reduced. H1299 cells were arrested in the G2/M phase and cell cycle progression was inhibited. Furthermore, the results of western blotting showed that nm23-H1 and vascular endothelial growth factor (VEGF) protein levels decreased in a dose-dependent manner, while the pro-apoptotic protein and anti-apoptotic protein ratios and the level of apoptosis-related caspase protein increased in a dose-dependent manner. In conclusion, our results indicated that PAP, as a natural marine bioactive substance, inhibited proliferation and induced apoptosis of human lung cancer H1299 cells. PAP is likely to be exploited as the functional food or adjuvant that may be used for prevention or treatment of human non-small cell lung cancer in the future. Full article
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Open AccessArticle 9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells
Mar. Drugs 2019, 17(2), 121; https://doi.org/10.3390/md17020121
Received: 11 January 2019 / Revised: 2 February 2019 / Accepted: 7 February 2019 / Published: 18 February 2019
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Abstract
β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer’s disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the [...] Read more.
β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer’s disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Aβ fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Aβ fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Aβ directly reduced Aβ oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Aβ42 with polar binding energy. Hydrogen bonds and π–π interactions between the key amino acid residues of Aβ42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Aβ oligomer, Aβ modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Aβ neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Aβ aggregation along with other target mechanisms. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Sponges)
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Open AccessArticle Briarenones A‒C, New Briarellin Diterpenoids from the Gorgonian Briareum violaceum
Mar. Drugs 2019, 17(2), 120; https://doi.org/10.3390/md17020120
Received: 9 January 2019 / Revised: 1 February 2019 / Accepted: 12 February 2019 / Published: 17 February 2019
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Abstract
Three new eunicellin-derived diterpenoids of briarellin type, briarenones A‒C (13), were isolated from a Formosan gorgonian Briareum violaceum. The chemical structures of the compounds were elucidated on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR. The [...] Read more.
Three new eunicellin-derived diterpenoids of briarellin type, briarenones A‒C (13), were isolated from a Formosan gorgonian Briareum violaceum. The chemical structures of the compounds were elucidated on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR. The absolute configuration of 1 was further confirmed by a single crystal X-ray diffraction analysis. The in vitro cytotoxic and anti-inflammatory potentialities of the isolated metabolites were tested against the growth of a limited panel of cancer cell lines and against the production of superoxide anions and elastase release in N-formyl-methionyl-leucyl-phenyl-alanine and cytochalasin B (fMLF/CB)-stimulated human neutrophils, respectively. Full article
(This article belongs to the Special Issue Marine Natural Products Discovery: In Honor of Late Prof. Tatsuo Higa)
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Open AccessArticle Biosynthesis of Nutraceutical Fatty Acids by the Oleaginous Marine Microalgae Phaeodactylum tricornutum Utilizing Hydrolysates from Organosolv-Pretreated Birch and Spruce Biomass
Mar. Drugs 2019, 17(2), 119; https://doi.org/10.3390/md17020119
Received: 28 December 2018 / Revised: 20 January 2019 / Accepted: 13 February 2019 / Published: 15 February 2019
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Abstract
Polyunsaturated fatty acids (PUFAs) are essential for human function, however they have to be provided through the diet. As their production from fish oil is environmentally unsustainable, there is demand for new sources of PUFAs. The aim of the present work was to [...] Read more.
Polyunsaturated fatty acids (PUFAs) are essential for human function, however they have to be provided through the diet. As their production from fish oil is environmentally unsustainable, there is demand for new sources of PUFAs. The aim of the present work was to establish the microalgal platform to produce nutraceutical-value PUFAs from forest biomass. To this end, the growth of Phaeodactylum tricornutum on birch and spruce hydrolysates was compared to autotrophic cultivation and glucose synthetic media. Total lipid generated by P. tricornutum grown mixotrophically on glucose, birch, and spruce hydrolysates was 1.21, 1.26, and 1.29 g/L, respectively. The highest eicosapentaenoic acid (EPA) production (256 mg/L) and productivity (19.69 mg/L/d) were observed on spruce hydrolysates. These values were considerably higher than those obtained from the cultivation without glucose (79.80 mg/L and 6.14 mg/L/d, respectively) and also from the photoautotrophic cultivation (26.86 mg/L and 2.44 mg/L/d, respectively). To the best of our knowledge, this is the first report describing the use of forest biomass as raw material for EPA and docosapentaenoic acid (DHA) production. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes - II)
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Open AccessReview Collagen of Extracellular Matrix from Marine Invertebrates and Its Medical Applications
Mar. Drugs 2019, 17(2), 118; https://doi.org/10.3390/md17020118
Received: 22 December 2018 / Revised: 25 January 2019 / Accepted: 5 February 2019 / Published: 14 February 2019
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Abstract
The extraction and purification of collagen are of great interest due to its biological function and medicinal applications. Although marine invertebrates are abundant in the animal kingdom, our knowledge of their extracellular matrix (ECM), which mainly contains collagen, is lacking. The functions of [...] Read more.
The extraction and purification of collagen are of great interest due to its biological function and medicinal applications. Although marine invertebrates are abundant in the animal kingdom, our knowledge of their extracellular matrix (ECM), which mainly contains collagen, is lacking. The functions of collagen isolated from marine invertebrates remain an untouched source of the proteinaceous component in the development of groundbreaking pharmaceuticals. This review will give an overview of currently used collagens and their future applications, as well as the methodological issues of collagens from marine invertebrates for potential drug discovery. Full article
(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)
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Open AccessCommunication Biocatalysis of Fucodian in Undaria pinnatifida Sporophyll Using Bifidobacterium longum RD47 for Production of Prebiotic Fucosylated Oligosaccharide
Mar. Drugs 2019, 17(2), 117; https://doi.org/10.3390/md17020117
Received: 24 January 2019 / Revised: 4 February 2019 / Accepted: 9 February 2019 / Published: 14 February 2019
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Abstract
Fucosylated oligosaccharide (FO) is known to selectively promote the growth of probiotic bacteria and is currently marketed as a functional health food and prebiotic in infant formula. Despite widespread interest in FO among functional food customers, high production costs due to high raw [...] Read more.
Fucosylated oligosaccharide (FO) is known to selectively promote the growth of probiotic bacteria and is currently marketed as a functional health food and prebiotic in infant formula. Despite widespread interest in FO among functional food customers, high production costs due to high raw material costs, especially those related to fucose, are a significant production issue. Therefore, several actions are required before efficient large-scale operations can occur, including (i) identification of inexpensive raw materials from which fucosylated oligosaccharides may be produced and (ii) development of production methods to which functional food consumers will not object (e.g., no genetically modified organisms (GMOs)). Undaria pinnatifida, commonly called Miyeok in Korea, is a common edible brown seaweed plentiful on the shores of the Korean peninsula. In particular, the sporophyll of Undaria pinnatifida contains significant levels of l-fucose in the form of fucoidan (a marine sulfated polysaccharide). If the l-fucose present in Undaria pinnatifida sporophyll was capable of being separated and recovered, l-fucose molecules could be covalently joined to other monosaccharides via glycosidic linkages, making this FO manufacturing technology of value in the functional food market. In our previous work, β-galactosidase (EC 3.2.2.23) from Bifidobacterium longum RD47 (B. longum RD47) was found to have transglycosylation activity and produce FO using purified l-fucose and lactose as substrates. In this research, crude fucodian hydrolysates were separated and recovered from edible seaweed (i.e., U. pinnatifida sporophyll). The extracted l-fucose was purified via gel permeation and ion exchange chromatographies and the recovered l-fucose was used to synthesize FO. B. longum RD47 successfully transglycosilated and produced FO using l-fucose derived from Undaria pinnatifida and lactose as substrates. To the best of our knowledge, this is the first report of synthesized FO using Bifidobacterium spp. Full article
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Open AccessArticle Antioxidative Peptides from Proteolytic Hydrolysates of False Abalone (Volutharpa ampullacea perryi): Characterization, Identification, and Molecular Docking
Mar. Drugs 2019, 17(2), 116; https://doi.org/10.3390/md17020116
Received: 27 December 2018 / Revised: 4 February 2019 / Accepted: 9 February 2019 / Published: 13 February 2019
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Abstract
Antioxidative peptides were produced from false abalone (Volutharpa ampullacea perryi) using enzymatic hydrolysis. Trypsin produced the most bioactive hydrolysates with the highest scavenging ABTS+• free radicals compared to pepsin, alcalase, neutrase, and flavourzyme. The response surface methodology studies on trypsin [...] Read more.
Antioxidative peptides were produced from false abalone (Volutharpa ampullacea perryi) using enzymatic hydrolysis. Trypsin produced the most bioactive hydrolysates with the highest scavenging ABTS+• free radicals compared to pepsin, alcalase, neutrase, and flavourzyme. The response surface methodology studies on trypsin hydrolysis indicated that the hydrolysis temperature, time, and pH were interacted with each other (p < 0.05), and the optimal conditions were hydrolysis at 51.8 °C for 4.1 h, pH 7.7 and the maximum predicted hydrolysis degree was 13.18% and ABTS+• scavenging activity of 79.42%. The optimized hydrolysate was subjected to ultrafiltration fractionation, and the fraction with MW < 3 kDa showed the highest ABTS+• scavenging activity. There were 193 peptide sequences identified from this peptide fraction and 133 of them were successfully docked onto human myeloperoxidase (MPO), an enzyme involved in forming reactive oxidants in vivo. The highest scored peptide, no. 39, consists of DTETGVPT. Its structure and molecular interactions with MPO active site were compared with previously characterized peptide hLF1-11. The interactions between peptide no. 39 and MPO include electrostatic charge, hydrogen bonds, and covalent bonds. The antioxidative peptide produced in this research may exert antioxidant activity in vivo due to its potential inhibition effect on MPO. Full article
(This article belongs to the Special Issue The Pharmacological Potential of Marine-Derived Peptides and Proteins)
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Open AccessFeature PaperReview Chemical Diversity and Biological Activities of Marine Sponges of the Genus Suberea: A Systematic Review
Mar. Drugs 2019, 17(2), 115; https://doi.org/10.3390/md17020115
Received: 16 January 2019 / Revised: 2 February 2019 / Accepted: 11 February 2019 / Published: 12 February 2019
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Abstract
Marine natural products (MNPs) continue to be in the spotlight in the global drug discovery endeavor. Currently, more than 30,000 structurally diverse secondary metabolites from marine sources have been isolated, making MNPs a profound, renewable source to investigate novel drug compounds. Marine sponges [...] Read more.
Marine natural products (MNPs) continue to be in the spotlight in the global drug discovery endeavor. Currently, more than 30,000 structurally diverse secondary metabolites from marine sources have been isolated, making MNPs a profound, renewable source to investigate novel drug compounds. Marine sponges of the genus Suberea (family: Aplysinellidae) are recognized as producers of bromotyrosine derivatives, which are considered distinct chemotaxonomic markers for the marine sponges belonging to the order Verongida. This class of compounds exhibits structural diversity, ranging from simple monomeric molecules to more complex molecular scaffolds, displaying a myriad of biological and pharmacological potentialities. In this review, a comprehensive literature survey covering the period of 1998–2018, focusing on the chemistry and biological/pharmacological activities of marine natural products from marine sponges of the genus Suberea, with special attention to the biogenesis of the different skeletons of halogenated compounds, is presented. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Sponges)
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Open AccessArticle Desertomycin G, a New Antibiotic with Activity against Mycobacterium tuberculosis and Human Breast Tumor Cell Lines Produced by Streptomyces althioticus MSM3, Isolated from the Cantabrian Sea Intertidal Macroalgae Ulva sp.
Mar. Drugs 2019, 17(2), 114; https://doi.org/10.3390/md17020114
Received: 15 January 2019 / Revised: 31 January 2019 / Accepted: 7 February 2019 / Published: 12 February 2019
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Abstract
The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G (1), with strong antibiotic activity against several clinically relevant antibiotic resistant pathogens are described herein. This new natural product was obtained from cultures of the marine actinomycete [...] Read more.
The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G (1), with strong antibiotic activity against several clinically relevant antibiotic resistant pathogens are described herein. This new natural product was obtained from cultures of the marine actinomycete Streptomyces althioticus MSM3, isolated from samples of the intertidal seaweed Ulva sp. collected in the Cantabrian Sea (Northeast Atlantic Ocean). Particularly interesting is its strong antibiotic activity against Mycobacterium tuberculosis clinical isolates, resistant to antibiotics in clinical use. To the best of our knowledge, this is the first report on a member of the desertomycin family displaying such activity. Additionally, desertomycin G shows strong antibiotic activities against other relevant Gram-positive clinical pathogens such as Corynebacterium urealyticum, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecium, Enterococcus faecalis, and Clostridium perfringens. Desertomycin G also displays moderate antibiotic activity against relevant Gram-negative clinical pathogens such as Bacteroides fragilis, Haemophilus influenzae and Neisseria meningitidis. In addition, the compound affects viability of tumor cell lines, such as human breast adenocarcinoma (MCF-7) and colon carcinoma (DLD-1), but not normal mammary fibroblasts. Full article
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Open AccessArticle Fourfold Filtered Statistical/Computational Approach for the Identification of Imidazole Compounds as HO-1 Inhibitors from Natural Products
Mar. Drugs 2019, 17(2), 113; https://doi.org/10.3390/md17020113
Received: 16 January 2019 / Revised: 8 February 2019 / Accepted: 9 February 2019 / Published: 12 February 2019
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Abstract
Over-regulation of Heme oxygenase 1 (HO-1) has been recently identified in many types of human cancer, and in these cases, poor clinical outcomes are normally reported. Indeed, the inhibition of HO-1 is being considered as an anticancer approach. Imidazole scaffold is normally present [...] Read more.
Over-regulation of Heme oxygenase 1 (HO-1) has been recently identified in many types of human cancer, and in these cases, poor clinical outcomes are normally reported. Indeed, the inhibition of HO-1 is being considered as an anticancer approach. Imidazole scaffold is normally present in most of the classical HO-1 inhibitors and seems indispensable to the inhibitory activity due to its strong interaction with the Fe(II) of the heme group. In this paper, we searched for new potentially HO-1 inhibitors among three different databases: Marine Natural Products (MNP), ZINC Natural Products (ZNP) and Super Natural II (SN2). 484,527 compounds were retrieved from the databases and filtered through four statistical/computational filters (2D descriptors, 2D-QSAR pharmacophoric model, 3D-QSAR pharmacophoric model, and docking). Different imidazole-based compounds were suggested by our methodology to be potentially active in inhibiting the HO-1, and the results have been rationalized by the bioactivity of the filtered molecules reported in the literature. Full article
(This article belongs to the Special Issue Molecular Docking in Marine Drug Discovery & Design)
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Open AccessArticle Development of a Mucoadhesive and In Situ Gelling Formulation Based on κ-Carrageenan for Application on Oral Mucosa and Esophagus Walls. I. A Functional In Vitro Characterization
Mar. Drugs 2019, 17(2), 112; https://doi.org/10.3390/md17020112
Received: 8 January 2019 / Revised: 29 January 2019 / Accepted: 6 February 2019 / Published: 12 February 2019
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Abstract
Oral mucositis and esophagitis represent the most frequent and clinically significant complications of cytoreductive chemotherapy and radiotherapy, which severely compromise the patient quality of life. The local application of polymeric gels could protect the injured tissues, alleviating the most painful symptoms. The present [...] Read more.
Oral mucositis and esophagitis represent the most frequent and clinically significant complications of cytoreductive chemotherapy and radiotherapy, which severely compromise the patient quality of life. The local application of polymeric gels could protect the injured tissues, alleviating the most painful symptoms. The present work aims at developing in situ gelling formulations for the treatment of oral mucositis and esophagitis. To reach these targets, κ-carrageenan (κ-CG) was selected as a polymer having wound healing properties and able to gelify in the presence of saliva ions, while hydroxypropyl cellulose (HPC) was used to improve the mucoadhesive properties of the formulations. CaCl2 was identified as a salt able to enhance the interaction between κ-CG and saliva ions. Different salt and polymer concentrations were investigated in order to obtain a formulation having the following features: (i) low viscosity at room temperature to facilitate administration, (ii) marked elastic properties at 37 °C, functional to a protective action towards damaged tissues, and (iii) mucoadhesive properties. Prototypes characterized by different κ-CG, HPC, and CaCl2 concentrations were subjected to a thorough rheological characterization and to in vitro mucoadhesion and washability tests. The overall results pointed out the ability of the developed formulations to produce a gel able to interact with saliva ions and to adhere to the biological substrates. Full article
(This article belongs to the Special Issue Marine Biopolymers and Drug Delivery)
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Open AccessArticle A Multi-Bioassay Integrated Approach to Assess the Antifouling Potential of the Cyanobacterial Metabolites Portoamides
Mar. Drugs 2019, 17(2), 111; https://doi.org/10.3390/md17020111
Received: 28 December 2018 / Revised: 31 January 2019 / Accepted: 8 February 2019 / Published: 12 February 2019
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Abstract
The cyclic peptides portoamides produced by the cyanobacterium Phormidium sp. LEGE 05292 were previously isolated and their ability to condition microcommunities by allelopathic effect was described. These interesting bioactive properties are, however, still underexplored as their biotechnological applications may be vast. This study [...] Read more.
The cyclic peptides portoamides produced by the cyanobacterium Phormidium sp. LEGE 05292 were previously isolated and their ability to condition microcommunities by allelopathic effect was described. These interesting bioactive properties are, however, still underexplored as their biotechnological applications may be vast. This study aims to investigate the antifouling potential of portoamides, given that a challenge in the search for new environmentally friendly antifouling products is to find non-toxic natural alternatives with the ability to prevent colonization of different biofouling species, from bacteria to macroinvertebrates. A multi-bioassay approach was applied to assess portoamides antifouling properties, marine ecotoxicity and molecular mode of action. Results showed high effectiveness in the prevention of mussel larvae settlement (EC50 = 3.16 µM), and also bioactivity towards growth and biofilm disruption of marine biofouling bacterial strains, while not showing toxicity towards both target and non-target species. Antifouling molecular targets in mussel larvae include energy metabolism modifications (failure in proton-transporting ATPases activity), structural alterations of the gills and protein and gene regulatory mechanisms. Overall, portoamides reveal a broad-spectrum bioactivity towards diverse biofouling species, including a non-toxic and reversible effect towards mussel larvae, showing potential to be incorporated as an active ingredient in antifouling coatings. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria II)
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Open AccessArticle In Silico Identification and Experimental Validation of (−)-Muqubilin A, a Marine Norterpene Peroxide, as PPARα/γ-RXRα Agonist and RARα Positive Allosteric Modulator
Mar. Drugs 2019, 17(2), 110; https://doi.org/10.3390/md17020110
Received: 16 January 2019 / Revised: 6 February 2019 / Accepted: 7 February 2019 / Published: 12 February 2019
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Abstract
The nuclear receptors (NRs) RARα, RXRα, PPARα, and PPARγ represent promising pharmacological targets for the treatment of neurodegenerative diseases. In the search for molecules able to simultaneously target all the above-mentioned NRs, we screened an in-house developed molecular database using a ligand-based approach, [...] Read more.
The nuclear receptors (NRs) RARα, RXRα, PPARα, and PPARγ represent promising pharmacological targets for the treatment of neurodegenerative diseases. In the search for molecules able to simultaneously target all the above-mentioned NRs, we screened an in-house developed molecular database using a ligand-based approach, identifying (−)-Muqubilin (Muq), a cyclic peroxide norterpene from a marine sponge, as a potential hit. The ability of this compound to stably and effectively bind these NRs was assessed by molecular docking and molecular dynamics simulations. Muq recapitulated all the main interactions of a canonical full agonist for RXRα and both PPARα and PPARγ, whereas the binding mode toward RARα showed peculiar features potentially impairing its activity as full agonist. Luciferase assays confirmed that Muq acts as a full agonist for RXRα, PPARα, and PPARγ with an activity in the low- to sub-micromolar range. On the other hand, in the case of RAR, a very weak agonist activity was observed in the micromolar range. Quite surprisingly, we found that Muq is a positive allosteric modulator for RARα, as both luciferase assays and in vivo analysis using a zebrafish transgenic retinoic acid (RA) reporter line showed that co-administration of Muq with RA produced a potent synergistic enhancement of RARα activation and RA signaling. Full article
(This article belongs to the Special Issue Molecular Docking in Marine Drug Discovery & Design)
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Open AccessArticle 5-O-Acetyl-Renieramycin T from Blue Sponge Xestospongia sp. Induces Lung Cancer Stem Cell Apoptosis
Mar. Drugs 2019, 17(2), 109; https://doi.org/10.3390/md17020109
Received: 14 January 2019 / Revised: 6 February 2019 / Accepted: 7 February 2019 / Published: 11 February 2019
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Abstract
Lung cancer is one of the most significant cancers as it accounts for almost 1 in 5 cancer deaths worldwide, with an increasing incident rate. Management of the cancer has been shown to frequently fail due to the ability of the cancer cells [...] Read more.
Lung cancer is one of the most significant cancers as it accounts for almost 1 in 5 cancer deaths worldwide, with an increasing incident rate. Management of the cancer has been shown to frequently fail due to the ability of the cancer cells to resist therapy as well as metastasis. Recent evidence has suggested that the poor response to the current treatment drugs and the ability to undergo metastasis are driven by cancer stem cells (CSCs) within the tumor. The discovery of novel compounds able to suppress CSCs and sensitize the chemotherapeutic response could be beneficial to the improvement of clinical outcomes. Herein, we report for the first time that 5-O-acetyl-renieramycin T isolated from the blue sponge Xestospongia sp. mediated lung cancer cell death via the induction of p53-dependent apoptosis. Importantly, 5-O-acetyl-renieramycin T induced the death of CSCs as represented by the CSC markers CD44 and CD133, while the stem cell transcription factor Nanog was also found to be dramatically decreased in 5-O-acetyl-renieramycin T-treated cells. We also found that such a CSC suppression was due to the ability of the compound to deplete the protein kinase B (AKT) signal. Furthermore, 5-O-acetyl-renieramycin T was able to significantly sensitize cisplatin-mediated apoptosis in the lung cancer cells. Together, the present research findings indicate that this promising compound from the marine sponge is a potential candidate for anti-cancer approaches. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Sponges)
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Open AccessArticle Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D3/D4 Receptors
Mar. Drugs 2019, 17(2), 108; https://doi.org/10.3390/md17020108
Received: 29 December 2018 / Revised: 28 January 2019 / Accepted: 7 February 2019 / Published: 10 February 2019
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Abstract
The G protein-coupled receptor (GPCR) family of proteins comprises signaling proteins that mediate cellular responses to various hormones and neurotransmitters, and serves as a prime target for drug discovery. Towards our goal of discovering secondary metabolites from natural sources that can function as [...] Read more.
The G protein-coupled receptor (GPCR) family of proteins comprises signaling proteins that mediate cellular responses to various hormones and neurotransmitters, and serves as a prime target for drug discovery. Towards our goal of discovering secondary metabolites from natural sources that can function as neuronal drugs, we evaluated the modulatory effect of eckol on various GPCRs via cell-based functional assays. In addition, we conducted in silico predictions to obtain molecular insights into the functional effects of eckol. Functional assays revealed that eckol had a concentration-dependent agonist effect on dopamine D3 and D4 receptors. The half maximal effective concentration (EC50) of eckol for the dopamine D3 and D4 receptors was 48.62 ± 3.21 and 42.55 ± 2.54 µM, respectively, while the EC50 values of dopamine as a reference agonist for these two receptors were 2.9 and 3.3 nM, respectively. In silico studies revealed that a low binding energy in addition to hydrophilic, hydrophobic, π–alkyl, and π–π T-shaped interactions are potential mechanisms by which eckol binds to the dopamine receptors to exert its agonist effects. Molecular dynamics (MD) simulation revealed that Phe346 of the dopamine receptors is important for binding of eckol, similar to eticlopride and dopamine. Our results collectively suggest that eckol is a potential D3/D4 agonist for the management of neurodegenerative diseases, such as Parkinson’s disease. Full article
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Open AccessArticle Biomolecular Composition and Revenue Explained by Interactions between Extrinsic Factors and Endogenous Rhythms of Saccharina latissima
Mar. Drugs 2019, 17(2), 107; https://doi.org/10.3390/md17020107
Received: 2 January 2019 / Revised: 31 January 2019 / Accepted: 1 February 2019 / Published: 10 February 2019
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Abstract
This review provides a systematic overview of the spatial and temporal variations in the content of biomolecular constituents of Saccharina latissima on the basis of 34 currently available scientific studies containing primary measurements. We demonstrate the potential revenue of seaweed production and biorefinery [...] Read more.
This review provides a systematic overview of the spatial and temporal variations in the content of biomolecular constituents of Saccharina latissima on the basis of 34 currently available scientific studies containing primary measurements. We demonstrate the potential revenue of seaweed production and biorefinery systems by compiling a product portfolio of high-value extract products. An investigation into the endogenous rhythms and extrinsic factors that impact the biomolecular composition of S. latissima is presented, and key performance factors for optimizing seaweed production are identified. Besides the provisioning ecosystem service, we highlight the contribution of green-engineered seaweed production systems to the mitigation of the ongoing and historical anthropogenic disturbances of the climate balance and nutrient flows. We conclude that there are risks of mismanagement, and we stress the importance and necessity of creating an adaptive ecosystem-based management framework within a triple-helix partnership for balancing the utilization of ecosystem services and long-term resilience of aquatic environment. Full article
(This article belongs to the Special Issue Discovery and Application of Macroalgae-Derived Natural Products)
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