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Mar. Drugs, Volume 15, Issue 12 (December 2017)

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Open AccessArticle Chemical Profiling and Bioactivity of Body Wall Lipids from Strongylocentrotus droebachiensis
Mar. Drugs 2017, 15(12), 365; doi:10.3390/md15120365
Received: 31 August 2017 / Revised: 9 November 2017 / Accepted: 15 November 2017 / Published: 24 November 2017
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Abstract
The lipids from gonads and polyhydroxynaphthoquinone pigments from body walls of sea urchins are intensively studied. However, little is known about the body wall (BW) lipids. Ethanol extract (55 °C) contained about equal amounts of saturated (SaFA) and monounsaturated fatty acids (MUFA) representing
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The lipids from gonads and polyhydroxynaphthoquinone pigments from body walls of sea urchins are intensively studied. However, little is known about the body wall (BW) lipids. Ethanol extract (55 °C) contained about equal amounts of saturated (SaFA) and monounsaturated fatty acids (MUFA) representing 60% of total fatty acids, with myristic, palmitic and eicosenoic acids as major SaFAs and MUFAs, respectively. Non-methylene-interrupted dienes (13%) were composed of eicosadienoic and docosadienoic acids. Long-chain polyunsaturated fatty acids (LC-PUFA) included two main components, n6 arachidonic and n3 eicosapentaenoic acids, even with equal concentrations (15 μg/mg) and a balanced n6/n3 PUFA ratio (0.86). The UPLC-ELSD analysis showed that a great majority of the lipids (80%) in the ethanolic extract were phosphatidylcholine (60 μg/mg) and phosphatidylethanolamine (40 μg/mg), while the proportion of neutral lipids remained lower than 20%. In addition, alkoxyglycerol derivatives—chimyl, selachyl, and batyl alcohols—were quantified. We have assumed that the mechanism of action of body wall lipids in the present study is via the inhibition of MAPK p38, COX-1, and COX-2. Our findings open the prospective to utilize this lipid fraction as a source for the development of drugs with anti-inflammatory activity. Full article
(This article belongs to the Special Issue Marine Lipids 2017)
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Open AccessFeature PaperArticle Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer’s Disease Therapeutic Agents
Mar. Drugs 2017, 15(12), 366; doi:10.3390/md15120366
Received: 6 October 2017 / Revised: 10 November 2017 / Accepted: 14 November 2017 / Published: 27 November 2017
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Abstract
Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity
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Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A–G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium, against various protein kinases involved in Alzheimer’s disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs. Full article
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Open AccessFeature PaperArticle Three New Malyngamides from the Marine Cyanobacterium Moorea producens
Mar. Drugs 2017, 15(12), 367; doi:10.3390/md15120367
Received: 28 September 2017 / Revised: 2 November 2017 / Accepted: 16 November 2017 / Published: 29 November 2017
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Abstract
Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1), 6-O-acetylmalyngamide 2 (2), and N-demethyl-isomalyngamide I (3), were isolated from the marine cyanobacterium Moorea producens. Their structures were determined by spectroscopic
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Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1), 6-O-acetylmalyngamide 2 (2), and N-demethyl-isomalyngamide I (3), were isolated from the marine cyanobacterium Moorea producens. Their structures were determined by spectroscopic analysis and chemical derivatization and degradation. These compounds stimulated glucose uptake in cultured L6 myotubes. In particular, 6,8-di-O-acetylmalyngamide 2 (1) showed potent activity and activated adenosine monophosphate-activated protein kinase (AMPK). Full article
(This article belongs to the Special Issue Marine Bioactive Natural Product Studies in Asia)
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Open AccessArticle α-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitory Activity of Plastoquinones from Marine Brown Alga Sargassum serratifolium
Mar. Drugs 2017, 15(12), 368; doi:10.3390/md15120368
Received: 25 October 2017 / Revised: 18 November 2017 / Accepted: 27 November 2017 / Published: 1 December 2017
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Abstract
Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-cancer,
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Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-cancer, anti-inflammatory, antioxidant, and neuroprotective activity. This study aims to investigate the anti-diabetic activity of S. serratifolium and its major constituents through inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, and ONOO-mediated albumin nitration. S. serratifolium ethanolic extract and fractions exhibited broad PTP1B and α-glucosidase inhibitory activity (IC50, 1.83~7.04 and 3.16~24.16 µg/mL for PTP1B and α-glucosidase, respectively). In an attempt to identify bioactive compounds, three plastoquinones (sargahydroquinoic acid, sargachromenol and sargaquinoic acid) were isolated from the active n-hexane fraction of S. serratifolium. All three plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the IC50 range of 5.14–14.15 µM, while sargachromenol and sargaquinoic acid showed dose-dependent inhibitory activity against α-glucosidase (IC50 42.41 ± 3.09 and 96.17 ± 3.48 µM, respectively). In the kinetic study of PTP1B enzyme inhibition, sargahydroquinoic acid and sargaquinoic acid led to mixed-type inhibition, whereas sargachromenol displayed noncompetitive-type inhibition. Moreover, plastoquinones dose-dependently inhibited ONOO-mediated albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B and α-glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the prevention and treatment of type 2 diabetes. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes II, 2017)
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Open AccessArticle The Marine Fungi Rhodotorula sp. (Strain CNYC4007) as a Potential Feed Source for Fish Larvae Nutrition
Mar. Drugs 2017, 15(12), 369; doi:10.3390/md15120369
Received: 31 August 2017 / Revised: 29 October 2017 / Accepted: 16 November 2017 / Published: 1 December 2017
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Abstract
Fish oil is used in the production of feed for cultured fish owing to its high polyunsaturated fatty acid content (PUFA). The over-exploitation of fisheries and events like “El Niño” are reducing the fish oil supply. Some marine microorganisms are considered potentially as
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Fish oil is used in the production of feed for cultured fish owing to its high polyunsaturated fatty acid content (PUFA). The over-exploitation of fisheries and events like “El Niño” are reducing the fish oil supply. Some marine microorganisms are considered potentially as alternative fatty acid sources. This study assesses a strain of Rhodotorula sp. (strain CNYC4007; 27% docosahexaenoic acid (DHA) of total fatty acids), as feed for fish larvae. The total length and ribonucleic acid (RNA)/deoxyribonucleic acid (DNA) ratio of Danio rerio larvae was determined at first feeding at six and 12 days old (post-yolk absorption larvae). Larvae fed with microencapsulated Rhodotorula sp. CNYC4007 had a significantly higher RNA/DNA ratio than control group (C1). At six days post-yolk absorption group, the RNA/DNA ratio of larvae fed with Rhodotorula sp. bioencapsulated in Brachionus sp. was significantly higher than control group fed with a commercial diet high in DHA (C2-DHA). Finally, at 12 days post-yolk absorption, the RNA/DNA ratio was significantly higher in larvae fed with Rhodotorula sp. CNYC4007 and C2-DHA (both bioencapsulated in Artemia sp. nauplii) than in control group (C1). These results suggest that Rhodotorula sp. CNYC4007 can be an alternative source of DHA for feeding fish at larval stage, providing a sustainable source of fatty acids. Full article
(This article belongs to the Special Issue Marine Lipids 2017)
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Open AccessFeature PaperArticle Chitosan Nanoparticles as a Mucoadhesive Drug Delivery System for Ocular Administration
Mar. Drugs 2017, 15(12), 370; doi:10.3390/md15120370
Received: 16 October 2017 / Revised: 6 November 2017 / Accepted: 14 November 2017 / Published: 1 December 2017
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Abstract
Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs’ bioavailability at the ocular surface.
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Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs’ bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (∆η). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties. Full article
(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)
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Open AccessArticle Inhibitors of Serine Proteases from a Microcystis sp. Bloom Material Collected from Timurim Reservoir, Israel
Mar. Drugs 2017, 15(12), 371; doi:10.3390/md15120371
Received: 23 October 2017 / Revised: 19 November 2017 / Accepted: 20 November 2017 / Published: 1 December 2017
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Abstract
Two new natural products, micropeptin TR1058 (1) and aeruginosin TR642 (2), were isolated from the hydrophilic extract of bloom material of Microcystis sp. collected from the Timurim water reservoir in Israel. The structures of compounds 1 and 2 were
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Two new natural products, micropeptin TR1058 (1) and aeruginosin TR642 (2), were isolated from the hydrophilic extract of bloom material of Microcystis sp. collected from the Timurim water reservoir in Israel. The structures of compounds 1 and 2 were determined using 1D and 2D NMR spectroscopy and HR ESI MS and MS/MS techniques. Micropeptin TR1058 (1) was extremely unstable under the isolation conditions, and several degradation products were identified. NMR analysis of aeruginosin TR642 (2) revealed a mixture of eight isomers, and elucidation of its structure was challenging. Aeruginosin TR642 contains a 4,5-didehydroaraginal subunit that has not been described before. Micropeptin TR1058 (1) inhibited chymotrypsin with an IC50 of 6.78 µM, and aeruginosin TR642 (2) inhibited trypsin and thrombin with inhibition concentration (IC50) values of 3.80 and 0.85 µM, respectively. The structures and biological activities of the new compounds are discussed. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria II, 2017)
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Open AccessArticle Chemical Diversity from a Chinese Marine Red Alga, Symphyocladia latiuscula
Mar. Drugs 2017, 15(12), 374; doi:10.3390/md15120374
Received: 3 November 2017 / Revised: 23 November 2017 / Accepted: 23 November 2017 / Published: 1 December 2017
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Abstract
This study describes an investigation into secondary metabolites that are produced by a marine red alga, Symphyocladia latiuscula, which was collected from coastal waters off Qingdao, China. A combination of normal, reversed phase, and gel chromatography was used to isolate six citric
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This study describes an investigation into secondary metabolites that are produced by a marine red alga, Symphyocladia latiuscula, which was collected from coastal waters off Qingdao, China. A combination of normal, reversed phase, and gel chromatography was used to isolate six citric acid derived natural products, aconitates A–F (16), together with two known and ten new polybrominated phenols, symphyocladins C/D (7a/b), and symphyocladins H–Q (8a/b, 9a/b and 1015), respectively. Structure elucidation was achieved by detailed spectroscopic (including X-ray crystallographic) analysis. We propose a plausible and convergent biosynthetic pathway involving a key quinone methide intermediate, linking aconitates and symphyocladins. Full article
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Open AccessArticle A New Dihydrochromone Dimer and Other Secondary Metabolites from Cultures of the Marine Sponge-Associated Fungi Neosartorya fennelliae KUFA 0811 and Neosartorya tsunodae KUFC 9213
Mar. Drugs 2017, 15(12), 375; doi:10.3390/md15120375
Received: 4 November 2017 / Revised: 21 November 2017 / Accepted: 24 November 2017 / Published: 1 December 2017
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Abstract
A previously unreported dihydrochromone dimer, paecilin E (1), was isolated, together with eleven known compounds: β-sitostenone, ergosta-4,6,8 (14), 22-tetraen-3-one, cyathisterone, byssochlamic acid, dehydromevalonic acid lactone, chevalone B, aszonalenin, dankasterone A (2), helvolic acid, secalonic acid A and fellutanine A,
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A previously unreported dihydrochromone dimer, paecilin E (1), was isolated, together with eleven known compounds: β-sitostenone, ergosta-4,6,8 (14), 22-tetraen-3-one, cyathisterone, byssochlamic acid, dehydromevalonic acid lactone, chevalone B, aszonalenin, dankasterone A (2), helvolic acid, secalonic acid A and fellutanine A, from the culture filtrate extract of the marine sponge-associated fungus Neosartorya fennelliae KUFA 0811. Nine previously reported metabolites, including a chromanol derivative (3), (3β, 5α, 22E), 3,5-dihydroxyergosta-7,22-dien-6-one (4), byssochlamic acid, hopan-3β,22-diol, chevalone C, sartorypyrone B, helvolic acid, lumichrome and the alkaloid harmane were isolated from the culture of the marine-sponge associated fungus Neosartorya tsunodae KUFC 9213. Paecilin E (1), dankasterone A (2), a chromanol derivative (3), (3β, 5α, 22E)-3,5-dihydroxyergosta-7,22-dien-6-one (4), hopan-3β,22-diol (5), lumichrome (6), and harmane (7) were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. While paecilin E (1) was active against S. aureus ATCC 29213 and E. faecalis ATCC 29212, dankastetrone A (2) was only effective against E. faecalis ATCC 29212 and the multidrug-resistant VRE E. faecalis A5/102. Both compounds neither inhibit biofilm mass production in any of the strains at the concentrations tested nor exhibit synergistic association with antibiotics. Full article
(This article belongs to the Special Issue Marine Products for Health and Beauty)
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Open AccessArticle The Anti-Inflammatory Effect and Structure of EPCP1-2 from Crypthecodinium cohnii via Modulation of TLR4-NF-κB Pathways in LPS-Induced RAW 264.7 Cells
Mar. Drugs 2017, 15(12), 376; doi:10.3390/md15120376
Received: 3 November 2017 / Revised: 15 November 2017 / Accepted: 17 November 2017 / Published: 1 December 2017
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Abstract
Exopolysaccharide from Crypthecodinium cohnii (EPCP1-2) is a marine exopolysaccharide that evidences a variety of biological activities. We isolated a neutral polysaccharide from the fermentation liquid of Crypthecodinium cohnii (CP). In this study, a polysaccharide that is derived from Crypthecodinium cohnii were analyzed and
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Exopolysaccharide from Crypthecodinium cohnii (EPCP1-2) is a marine exopolysaccharide that evidences a variety of biological activities. We isolated a neutral polysaccharide from the fermentation liquid of Crypthecodinium cohnii (CP). In this study, a polysaccharide that is derived from Crypthecodinium cohnii were analyzed and its anti-inflammatory effect was evaluated on protein expression of toll-like receptor 4 and nuclear factor κB pathways in macrophages. The structural characteristics of EPCP1-2 were characterized by GC (gas chromatography) and GC-MS (gas Chromatography-Mass Spectrometer) analyses. The molecular weight was about 82.5 kDa. The main chain of EPCP1-2 consisted of (1→6)-linked mannopyranosyl, (1→6)-linked glucopyranosyl, branched-chain consisted of (1→3,6)-linked galactopyranosyl and terminal consisted of t-l-Rhapyranosyl. The in vitro anti-inflammatory activity was representated through assay of proliferation rate, pro-inflammatory factor (NO) and expressions of proteins on RAW 264.7, the macrophage cell line. The results revealed that EPCP1-2 exhibited significant anti-inflammatory activity by regulating the expression of toll-like receptor 4, mitogen-activated protein kinases, and Nuclear Factor-κB protein. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessArticle Optimization of Collagenase Production by Pseudoalteromonas sp. SJN2 and Application of Collagenases in the Preparation of Antioxidative Hydrolysates
Mar. Drugs 2017, 15(12), 377; doi:10.3390/md15120377
Received: 18 October 2017 / Revised: 6 November 2017 / Accepted: 29 November 2017 / Published: 4 December 2017
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Abstract
Collagenases are the most important group of commercially-produced enzymes. However, even though biological resources are abundant in the sea, very few of these commercially popular enzymes are from marine sources, especially from marine bacteria. We optimized the production of marine collagenases by Pseudoalteromonas
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Collagenases are the most important group of commercially-produced enzymes. However, even though biological resources are abundant in the sea, very few of these commercially popular enzymes are from marine sources, especially from marine bacteria. We optimized the production of marine collagenases by Pseudoalteromonas sp. SJN2 and investigated the antioxidant activities of the hydrolysates. Media components and culture conditions associated with marine collagenase production by Pseudoalteromonas sp. SJN2 were optimized by statistical methods, namely Plackett–Burman design and response surface methodology (RSM). Furthermore, the marine collagenases produced by Pseudoalteromonas sp. SJN2 were seen to efficiently hydrolyze marine collagens extracted from fish by-products, and remarkable antioxidant capacities of the enzymatic hydrolysates were shown by DPPH radical scavenging and oxygen radical absorbance capacity (ORAC) tests. The final optimized fermentation conditions were as follows: soybean powder, 34.23 g·L−1; culture time, 3.72 d; and temperature, 17.32 °C. Under the optimal fermentation conditions, the experimental collagenase yield obtained was 322.58 ± 9.61 U·mL−1, which was in agreement with the predicted yield of 306.68 U·mL−1. Collagen from Spanish mackerel bone, seabream scale and octopus flesh also showed higher DPPH radical scavenging rates and ORAC values after hydrolysis by the collagenase. This study may have implications for the development and use of marine collagenases. Moreover, seafood waste containing beneficial collagen could be used to produce antioxidant peptides by proteolysis. Full article
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Open AccessArticle Lobocrassin B Induces Apoptosis of Human Lung Cancer and Inhibits Tumor Xenograft Growth
Mar. Drugs 2017, 15(12), 378; doi:10.3390/md15120378
Received: 19 September 2017 / Revised: 15 November 2017 / Accepted: 28 November 2017 / Published: 4 December 2017
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Abstract
Lobocrassin B, a natural cembrane-type compound isolated from the soft coral Lobophytum crassum, has been shown to have significant biological effects, including anticancer activity. As the most common cause of cancer mortality worldwide, lung cancer remains a major concern threatening human health.
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Lobocrassin B, a natural cembrane-type compound isolated from the soft coral Lobophytum crassum, has been shown to have significant biological effects, including anticancer activity. As the most common cause of cancer mortality worldwide, lung cancer remains a major concern threatening human health. In the current study, we conducted in vitro experiments to demonstrate the inhibiting effect of Lobocrassin B on CL1-5 and H520 human lung cancer cells growth and to explore the underlying mechanisms, as well as in nude mice bearing CL1-5 tumor xenografts. Lobocrassin B exerted cytotoxic effects on lung cancer cells, as shown by decreasing cell viability, and inducing apoptosis, oxidative stress and mitochondrial dysfunction. In addition, the increased level of Bax, cleaved caspase-3, -9 and -8, and the suppression of Bcl-2 were observed in the Lobocrassin B treated cells. Moreover, in vivo assays verified the significance of these results, revealing that Lobocrassin B inhibited CL1-5 tumor xenograft growth and that inhibitory effects were accompanied by a marked increase in tumor cell apoptosis. In conclusion, the results suggested that Lobocrassin B could be a potential anticancer compound for its propensity to inhibit growth and induce apoptosis in human lung cancer cells. Full article
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Open AccessArticle Three New Cytotoxic Steroidal Glycosides Isolated from Conus pulicarius Collected in Kosrae, Micronesia
Mar. Drugs 2017, 15(12), 379; doi:10.3390/md15120379
Received: 23 October 2017 / Revised: 15 November 2017 / Accepted: 23 November 2017 / Published: 4 December 2017
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Abstract
Three new sulfated steroidal glycosides (35), along with known cholesterol derivatives (1,2), were isolated from the visceral extract of the cone snail Conus pulicarius. The structure of each new compound was elucidated by nuclear
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Three new sulfated steroidal glycosides (35), along with known cholesterol derivatives (1,2), were isolated from the visceral extract of the cone snail Conus pulicarius. The structure of each new compound was elucidated by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The three new compounds exhibited significant in vitro cytotoxicity (GI50 values down to 0.49 μM) against the K562 human leukemia cell line. Full article
(This article belongs to the Special Issue Marine Glycosides)
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Open AccessArticle Bioinspiring Chondrosia reniformis (Nardo, 1847) Collagen-Based Hydrogel: A New Extraction Method to Obtain a Sticky and Self-Healing Collagenous Material
Mar. Drugs 2017, 15(12), 380; doi:10.3390/md15120380
Received: 30 September 2017 / Revised: 28 October 2017 / Accepted: 16 November 2017 / Published: 4 December 2017
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Abstract
Collagen is a natural and abundant polymer that serves multiple functions in both invertebrates and vertebrates. As collagen is the natural scaffolding for cells, collagen-based hydrogels are regarded as ideal materials for tissue engineering applications since they can mimic the natural cellular microenvironment.
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Collagen is a natural and abundant polymer that serves multiple functions in both invertebrates and vertebrates. As collagen is the natural scaffolding for cells, collagen-based hydrogels are regarded as ideal materials for tissue engineering applications since they can mimic the natural cellular microenvironment. Chondrosia reniformis is a marine demosponge particularly rich in collagen, characterized by the presence of labile interfibrillar crosslinks similarly to those described in the mutable collagenous tissues (MCTs) of echinoderms. As a result single fibrils can be isolated using calcium-chelating and disulphide-reducing chemicals. In the present work we firstly describe a new extraction method that directly produces a highly hydrated hydrogel with interesting self-healing properties. The materials obtained were then biochemically and rheologically characterized. Our investigation has shown that the developed extraction procedure is able to extract collagen as well as other proteins and Glycosaminoglycans (GAG)-like molecules that give the collagenous hydrogel interesting and new rheological properties when compared to other described collagenous materials. The present work motivates further in-depth investigations towards the development of a new class of injectable collagenous hydrogels with tailored specifications. Full article
(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)
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Open AccessArticle Metabolites with Insecticidal Activity from Aspergillus fumigatus JRJ111048 Isolated from Mangrove Plant Acrostichum specioum Endemic to Hainan Island
Mar. Drugs 2017, 15(12), 381; doi:10.3390/md15120381
Received: 3 November 2017 / Revised: 25 November 2017 / Accepted: 1 December 2017 / Published: 6 December 2017
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Abstract
Fungi residing in mangroves are considered to be a bank of novel bioactive natural products. In the screening for bioactive metabolites from mangrove-derived fungi, the ethyl acetate extract of the fermentation broth of Aspergillus fumigatus JRJ111048, a fungus isolated from the leaves of
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Fungi residing in mangroves are considered to be a bank of novel bioactive natural products. In the screening for bioactive metabolites from mangrove-derived fungi, the ethyl acetate extract of the fermentation broth of Aspergillus fumigatus JRJ111048, a fungus isolated from the leaves of the mangrove plant Acrostichum specioum endemic to Hainan island, was found to possess insecticidal activity against Spodoptera litura. Bioactivity-guided isolation lead to the discovery of seven metabolites 17, including one new anhydride derivative aspergide (1), one new lipid amide 11-methyl-11-hydroxyldodecanoic acid amide (2), and five known compounds; α-ethyl glucoside (3), spiculisporic acid B (4), spiculisporic acid C (5), spiculisporic acid (6), and secospiculisporic acid B (7). Their structures were established by NMR spectroscopic and MS analyses, and by comparison of previously reported data. Insecticidal activity against S. litura and antifungal activity of these compounds were investigated. As a result, the new compound 1 showed potent insecticidal activity against newly hatched larvae of S. litura, and compound 4 displayed weak antifungal activity against Candida albicans. Full article
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Open AccessArticle Isolation of Petrocidin A, a New Cytotoxic Cyclic Dipeptide from the Marine Sponge-Derived Bacterium Streptomyces sp. SBT348
Mar. Drugs 2017, 15(12), 383; doi:10.3390/md15120383
Received: 25 October 2017 / Revised: 6 November 2017 / Accepted: 16 November 2017 / Published: 6 December 2017
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Abstract
A new cyclic dipeptide, petrocidin A (1), along with three known compounds—2,3-dihydroxybenzoic acid (2), 2,3-dihydroxybenzamide (3), and maltol (4)—were isolated from the solid culture of Streptomyces sp. SBT348. The strain Streptomyces sp. SBT348 had been
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A new cyclic dipeptide, petrocidin A (1), along with three known compounds—2,3-dihydroxybenzoic acid (2), 2,3-dihydroxybenzamide (3), and maltol (4)—were isolated from the solid culture of Streptomyces sp. SBT348. The strain Streptomyces sp. SBT348 had been prioritized in a strain collection of 64 sponge-associated actinomycetes based on its distinct metabolomic profile using liquid chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). The absolute configuration of all α-amino acids was determined by HPLC analysis after derivatization with Marfey’s reagent and comparison with commercially available reference amino acids. Structure elucidation was pursued in the presented study by mass spectrometry and NMR spectral data. Petrocidin A (1) and 2,3-dihydroxybenzamide (3) exhibited significant cytotoxicity towards the human promyelocytic HL-60 and the human colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential of sponge-associated actinomycetes for the discovery of novel and pharmacologically active natural products. Full article
(This article belongs to the Special Issue Bioprospecting of Marine Microorganisms)
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Open AccessArticle The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV’s)
Mar. Drugs 2017, 15(12), 385; doi:10.3390/md15120385
Received: 5 September 2017 / Revised: 1 December 2017 / Accepted: 2 December 2017 / Published: 8 December 2017
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Abstract
This study investigated in vitro effects of freshwater alga Cladophora glomerata water extract enriched during a biosorption process in Cr(III) trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs) and extracellular microvesicles (MVs) in equine metabolic syndrome-affected horses. Chemical characterisation
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This study investigated in vitro effects of freshwater alga Cladophora glomerata water extract enriched during a biosorption process in Cr(III) trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs) and extracellular microvesicles (MVs) in equine metabolic syndrome-affected horses. Chemical characterisation of natural Cladophora glomerata was performed with special emphasis on: vitamin C, vitamin E, total phenols, fatty acids, free and protein-bound amino acids as well as measured Cr in algal biomass. To examine the influence of Cladophora glomerata water extracts, in vitro viability, oxidative stress factor accumulation, apoptosis, inflammatory response, biogenesis of mitochondria, autophagy in ASCs of EMS and secretory activity manifested by MV release were investigated. For this purpose, various methods of molecular biology and microscopic observations (i.e., immunofluorescence staining, SEM, TEM, FIB observations, mRNA and microRNA expression by RT-qPCR) were applied. The extract of Cladophora glomerata enriched with Cr(III) ions reduced apoptosis and inflammation in ASCs of EMS horses through improvement of mitochondrial dynamics, decreasing of PDK4 expression and reduction of endoplastic reticulum stress. Moreover, it was found, that Cladophora glomerata and Cr(III) induce antioxidative protection coming from enhanced SOD activity Therefore, Cladophora glomerata enriched with Cr(III) ions might become an interesting future therapeutic agent in the pharmacological treatment of EMS horses. Full article
(This article belongs to the Special Issue Marine Compounds Used in Biosorption)
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Open AccessArticle Deep Sea Water Improves Abnormalities in Lipid Metabolism through Lipolysis and Fatty Acid Oxidation in High-Fat Diet-Induced Obese Rats
Mar. Drugs 2017, 15(12), 386; doi:10.3390/md15120386
Received: 30 October 2017 / Revised: 29 November 2017 / Accepted: 5 December 2017 / Published: 11 December 2017
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Abstract
Deep sea water (DSW) is a natural marine resource that has been utilized for food, agriculture, cosmetics, and medicine. The aim of this study was to investigate whether DSW has beneficial lipid metabolic effects in an animal model. Our previous in vitro study
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Deep sea water (DSW) is a natural marine resource that has been utilized for food, agriculture, cosmetics, and medicine. The aim of this study was to investigate whether DSW has beneficial lipid metabolic effects in an animal model. Our previous in vitro study indicated that DSW significantly decreased the intracellular triglyceride and glycerol-3-phosphate dehydrogenase activity in 3T3-L1 adipocytes. DSW also inhibited the gene levels of adipocyte differentiation, lipogenesis, and adipocytokines, and up-regulated gene levels of lipolysis and fatty acid oxidation. In the present study, the results showed that body weight, liver, adipose tissue, hepatic triglycerides and cholesterol, and serum parameters in the high-fat diet (HFD) + DSW groups were significantly lower compared to the HFD group. Moreover, the fecal output of total lipids, triglycerides, and cholesterol in the HFD + DSW groups was significantly higher than that of the HFD group. Regarding gene expression, DSW significantly increased the gene levels of lipolysis and fatty acid oxidation, and decreased the gene levels of adipocytokine in the adipose tissue of rats with HFD-induced obesity. These results indicate a potential molecular mechanism by which DSW can suppress obesity in rats with HFD-induced obesity through lipolysis and fatty acid oxidation. Full article
(This article belongs to the Special Issue Marine Drugs in the Management of Metabolic Diseases)
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Open AccessCommunication Collismycin C from the Micronesian Marine Bacterium Streptomyces sp. MC025 Inhibits Staphylococcus aureus Biofilm Formation
Mar. Drugs 2017, 15(12), 387; doi:10.3390/md15120387
Received: 22 November 2017 / Revised: 3 December 2017 / Accepted: 7 December 2017 / Published: 12 December 2017
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Abstract
Biofilm formation plays a critical role in antimicrobial resistance in Staphylococcus aureus. Here, we investigated the potential of crude extracts of 79 Micronesian marine microorganisms to inhibit S. aureus biofilm formation. An extract of Streptomyces sp. MC025 inhibited S. aureus biofilm formation.
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Biofilm formation plays a critical role in antimicrobial resistance in Staphylococcus aureus. Here, we investigated the potential of crude extracts of 79 Micronesian marine microorganisms to inhibit S. aureus biofilm formation. An extract of Streptomyces sp. MC025 inhibited S. aureus biofilm formation. Bioactivity-guided isolation led to the isolation of a series of 2,2′-bipyridines: collismycin B (1), collismycin C (2), SF2738 D (3), SF2738 F (4), pyrisulfoxin A (5), and pyrisulfoxin B (6). Among these bipyridines, collismycin C (2) was found to be the most effective inhibitor of biofilm formation by methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA), and this compound inhibited MRSA biofilm formation by more than 90% at a concentration of 50 μg/mL. The antibiofilm activity of collismycin C was speculated to be related to iron acquisition and the presence and position of the hydroxyl group of 2,2′-bipyridines. Full article
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Review

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Open AccessReview Structural Insights into the Cytotoxic Mechanism of Vibrio parahaemolyticus PirAvp and PirBvp Toxins
Mar. Drugs 2017, 15(12), 373; doi:10.3390/md15120373
Received: 3 October 2017 / Revised: 14 November 2017 / Accepted: 17 November 2017 / Published: 1 December 2017
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Abstract
In aquaculture, shrimp farming is a popular field. The benefits of shrimp farming include a relatively short grow-out time, high sale price, and good cost recovery. However, outbreaks of serious diseases inflict serious losses, and acute hepatopancreatic necrosis disease (AHPND) is an emerging
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In aquaculture, shrimp farming is a popular field. The benefits of shrimp farming include a relatively short grow-out time, high sale price, and good cost recovery. However, outbreaks of serious diseases inflict serious losses, and acute hepatopancreatic necrosis disease (AHPND) is an emerging challenge to this industry. In South American white shrimp (Penaeus vannamei) and grass shrimp (Penaeus monodon), this disease has a 70–100% mortality. The pathogenic agent of AHPND is a specific strain of Vibrio parahaemolyticus which contains PirAvp and PirBvp toxins encoded in the pVA1 plasmid. PirAvp and PirBvp have been shown to cause the typical histological symptoms of AHPND in infected shrimps, and in this review, we will focus on our structural understanding of these toxins. By analyzing their structures, a possible cytotoxic mechanism, as well as strategies for anti-AHPND drug design, is proposed. Full article
(This article belongs to the Special Issue Marine Bacterial Toxins)
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Open AccessReview Terpenoids from Octocorals of the Genus Pachyclavularia
Mar. Drugs 2017, 15(12), 382; doi:10.3390/md15120382
Received: 2 November 2017 / Revised: 1 December 2017 / Accepted: 4 December 2017 / Published: 5 December 2017
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Abstract
In this paper, we reviewed natural compounds isolated from octocorals belonging to the genus Pachyclavularia, including 20 cembrane-, 39 briarane-, and eight briarellin-related diterpenoids, and one secosterol. The chemical constituents of these 68 secondary metabolites, and their names, structures, and bioactivities, along
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In this paper, we reviewed natural compounds isolated from octocorals belonging to the genus Pachyclavularia, including 20 cembrane-, 39 briarane-, and eight briarellin-related diterpenoids, and one secosterol. The chemical constituents of these 68 secondary metabolites, and their names, structures, and bioactivities, along with studies of their biological activities, are summarized in this review. Based on the literature, many of these compounds possess bioactivities, including anti-inflammation properties, cytotoxicity, and ichthyotoxicity, suggesting that they may have the potential to be developed into biomedical agents for treatment. Full article
(This article belongs to the Special Issue Development and Application of Herbal Medicine from Marine Origin)
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Open AccessReview The Potential of Indonesian Heterobranchs Found around Bunaken Island for the Production of Bioactive Compounds
Mar. Drugs 2017, 15(12), 384; doi:10.3390/md15120384
Received: 14 July 2017 / Revised: 27 November 2017 / Accepted: 28 November 2017 / Published: 7 December 2017
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Abstract
The species diversity of marine heterobranch sea slugs found on field trips around Bunaken Island (North Sulawesi, Indonesia) and adjacent islands of the Bunaken National Marine Park forms the basis of this review. In a survey performed in 2015, 80 species from 23
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The species diversity of marine heterobranch sea slugs found on field trips around Bunaken Island (North Sulawesi, Indonesia) and adjacent islands of the Bunaken National Marine Park forms the basis of this review. In a survey performed in 2015, 80 species from 23 families were collected, including 17 new species. Only three of these have been investigated previously in studies from Indonesia. Combining species diversity with a former study from 2003 reveals in total 140 species from this locality. The diversity of bioactive compounds known and yet to be discovered from these organisms is summarized and related to the producer if known or suspected (might it be down the food chain, de novo synthesised from the slug or an associated bacterium). Additionally, the collection of microorganisms for the discovery of natural products of pharmacological interest from this hotspot of biodiversity that is presented here contains more than 50 species that have never been investigated before in regard to bioactive secondary metabolites. This highlights the great potential of the sea slugs and the associated microorganisms for the discovery of natural products of pharmacological interest from this hotspot of biodiversity. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Open AccessReview Recent Advances in Marine Algae Polysaccharides: Isolation, Structure, and Activities
Mar. Drugs 2017, 15(12), 388; doi:10.3390/md15120388 (registering DOI)
Received: 5 November 2017 / Revised: 5 December 2017 / Accepted: 6 December 2017 / Published: 13 December 2017
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Abstract
Marine algae have attracted a great deal of interest as excellent sources of nutrients. Polysaccharides are the main components in marine algae, hence a great deal of attention has been directed at isolation and characterization of marine algae polysaccharides because of their numerous
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Marine algae have attracted a great deal of interest as excellent sources of nutrients. Polysaccharides are the main components in marine algae, hence a great deal of attention has been directed at isolation and characterization of marine algae polysaccharides because of their numerous health benefits. In this review, extraction and purification approaches and chemico-physical properties of marine algae polysaccharides (MAPs) are summarized. The biological activities, which include immunomodulatory, antitumor, antiviral, antioxidant, and hypolipidemic, are also discussed. Additionally, structure-function relationships are analyzed and summarized. MAPs’ biological activities are closely correlated with their monosaccharide composition, molecular weights, linkage types, and chain conformation. In order to promote further exploitation and utilization of polysaccharides from marine algae for functional food and pharmaceutical areas, high efficiency, and low-cost polysaccharide extraction and purification methods, quality control, structure-function activity relationships, and specific mechanisms of MAPs activation need to be extensively investigated. Full article
(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)
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Other

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Open AccessShort Note Effect of Marine-Derived Ice-Binding Proteins on the Cryopreservation of Marine Microalgae
Mar. Drugs 2017, 15(12), 372; doi:10.3390/md15120372
Received: 30 September 2017 / Revised: 17 November 2017 / Accepted: 23 November 2017 / Published: 1 December 2017
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Abstract
Ice-binding protein (IBPs) protect cells from cryo-injury during cryopreservation by inhibiting ice recrystallization (IR), which is a main cause of cell death. In the present study, we employed two IBPs, one, designated LeIBP from Arctic yeast, and the other, designated FfIBP from Antarctic
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Ice-binding protein (IBPs) protect cells from cryo-injury during cryopreservation by inhibiting ice recrystallization (IR), which is a main cause of cell death. In the present study, we employed two IBPs, one, designated LeIBP from Arctic yeast, and the other, designated FfIBP from Antarctic sea ice bacterium, in the cryopreservation of three economically valuable marine microalgae, Isochrysis galbana, Pavlova viridis, and Chlamydomonas coccoides. Both of the IBPs showed IR inhibition in f/2 medium containing 10% DMSO, indicating that they retain their function in freezing media. Microalgal cells were frozen in 10% DMSO with or without IBP. Post-thaw viability exhibited that the supplementation of IBPs increased the viability of all cryopreserved cells. LeIBP was effective in P. viridis and C. coccoides, while FfIBP was in I. galbana. The cryopreservative effect was more drastic with P. viridis when 0.05 mg/mL LeIBP was used. These results clearly demonstrate that IBPs could improve the viability of cryopreserved microalgal cells. Full article
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