Marine Drugs

15 pages, 1323 KiB

Open AccessArticle

Astaxanthin Counteracts Excitotoxicity and Reduces the Ensuing Increases in Calcium Levels and Mitochondrial Reactive Oxygen Species Generation

by Francisca García, Pedro Lobos, Alejandra Ponce, Karla Cataldo, Daniela Meza, Patricio Farías, Carolina Estay, Felipe Oyarzun-Ampuero, Rodrigo Herrera-Molina, Andrea Paula-Lima, Álvaro O. Ardiles, Cecilia Hidalgo, Tatiana Adasme and Pablo Muñoz

Mar. Drugs 2020, 18(6), 335; https://doi.org/10.3390/md18060335 - 26 Jun 2020

Cited by 16 | Viewed by 3299

Abstract

Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca [...] Read more.

Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca²⁺ concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca²⁺ dysregulation. Here, we studied whether ASX protects neurons from N-methyl-D-aspartate (NMDA)-induced excitotoxicity, a noxious process which decreases cellular viability, alters gene expression and promotes excessive mROS production. Incubation of the neuronal cell line SH-SY5Y with NMDA decreased cellular viability and increased mitochondrial superoxide production; pre-incubation with ASX prevented these effects. Additionally, incubation of SH-SY5Y cells with ASX effectively reduced the basal mROS production and prevented hydrogen peroxide-induced cell death. In primary hippocampal neurons, transfected with a genetically encoded cytoplasmic Ca²⁺ sensor, ASX also prevented the increase in intracellular Ca²⁺ concentration induced by NMDA. We suggest that, by preventing the noxious mROS and Ca²⁺ increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca²⁺ homeostasis and ROS generation. Full article

(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)

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21 pages, 2422 KiB

Open AccessArticle

Degradation of Sargassum crassifolium Fucoidan by Ascorbic Acid and Hydrogen Peroxide, and Compositional, Structural, and In Vitro Anti-Lung Cancer Analyses of the Degradation Products

by Tien-Chiu Wu, Yong-Han Hong, Yung-Hsiang Tsai, Shu-Ling Hsieh, Ren-Han Huang, Chia-Hung Kuo and Chun-Yung Huang

Mar. Drugs 2020, 18(6), 334; https://doi.org/10.3390/md18060334 - 26 Jun 2020

Cited by 14 | Viewed by 3080

Abstract

Fucoidans possess multiple biological functions including anti-cancer activity. Moreover, low-molecular-weight fucoidans are reported to possess more bioactivities than native fucoidans. In the present study, a native fucoidan (SC) was extracted from Sargassum crassifolium pretreated by single-screw extrusion, and three degraded fucoidans, namely, SCA [...] Read more.

Fucoidans possess multiple biological functions including anti-cancer activity. Moreover, low-molecular-weight fucoidans are reported to possess more bioactivities than native fucoidans. In the present study, a native fucoidan (SC) was extracted from Sargassum crassifolium pretreated by single-screw extrusion, and three degraded fucoidans, namely, SCA (degradation of SC by ascorbic acid), SCH (degradation of SC by hydrogen peroxide), and SCAH (degradation of SC by ascorbic acid + hydrogen peroxide), were produced. The extrusion pretreatment can increase the extraction yield of fucoidan by approximately 4.2-fold as compared to the non-extruded sample. Among SC, SCA, SCH, and SCAH, the chemical compositions varied but structural features were similar. SC, SCA, SCH, and SCAH showed apoptotic effects on human lung carcinoma A-549 cells, as illustrated by loss of mitochondrial membrane potential (MMP), decreased B-cell leukemia-2 (Bcl-2) expression, increased cytochrome c release, increased active caspase-9 and -3, and increased late apoptosis of A-549 cells. In general, SCA was found to exhibit high cytotoxicity to A-549 cells and a strong ability to suppress Bcl-2 expression. SCA also showed high efficacy to induce cytochrome c release, activate caspase-9 and -3, and promote late apoptosis of A-549 cells. Therefore, our data suggest that SCA could have an adjuvant therapeutic potential in the treatment of lung cancer. Additionally, we explored that the Akt/mammalian target of rapamycin (mTOR) signaling pathway is involved in SC-, SCA-, SCH-, and SCAH-induced apoptosis of A-549 cells. Full article

(This article belongs to the Special Issue Fucoidans)

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18 pages, 4103 KiB

Open AccessArticle

Protective Effect of Fucoidan against MPP⁺-Induced SH-SY5Y Cells Apoptosis by Affecting the PI3K/Akt Pathway

by Huaide Liu, Jing Wang, Quanbin Zhang, Lihua Geng, Yue Yang and Ning Wu

Mar. Drugs 2020, 18(6), 333; https://doi.org/10.3390/md18060333 - 25 Jun 2020

Cited by 13 | Viewed by 2944

Abstract

The main pathologic changes of the Parkinson’s disease (PD) is dopaminergic (DA) neurons lost. Apoptosis was one of the important reasons involved in the DA lost. Our previous study found a fucoidan fraction sulfated heterosaccharide (UF) had neuroprotective activity. The aim of this [...] Read more.

The main pathologic changes of the Parkinson’s disease (PD) is dopaminergic (DA) neurons lost. Apoptosis was one of the important reasons involved in the DA lost. Our previous study found a fucoidan fraction sulfated heterosaccharide (UF) had neuroprotective activity. The aim of this study was to clarify the mechanism of UF on DA neurons using human dopaminergic neuroblastoma (SH-SY5Y) cells a typical as a PD cellular model. Results showed that UF prevented MPP⁺-induced SH-SY5Y cells apoptosis and cell death. Additionally, UF pretreated cells increased phosphorylation of Akt, PI3K and NGF, which means UF-treated active PI3K–Akt pathway. Moreover, UF treated cells decreased the expression of apoptosis-associated protein, such as the ratio of Bax/Bcl-2, GSK3β, caspase-3 and p53 nuclear induced by MPP⁺. This effect was partially blocked by PI3K inhibitor LY294002. Our data suggested that protective effect of UF against MPP⁺-induced SH-SY5Y cells death by affecting the PI3K–Akt pathway. These findings contribute to a better understanding of the critical roles of UF in treating PD and may elucidate the molecular mechanisms of UF effects in PD. Full article

(This article belongs to the Special Issue Fucoidans)

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10 pages, 795 KiB

Open AccessArticle

Efficient Preparation of Bafilomycin A1 from Marine Streptomyces lohii Fermentation Using Three-Phase Extraction and High-Speed Counter-Current Chromatography

by Ye Yuan, Xiaoping He, Tingting Wang, Xingwang Zhang, Zhong Li, Xiaoqing Xu, Weiyan Zhang, Xiaojun Yan, Shengying Li and Shan He

Mar. Drugs 2020, 18(6), 332; https://doi.org/10.3390/md18060332 - 25 Jun 2020

Cited by 11 | Viewed by 2588

Abstract

An efficient strategy was developed for the rapid separation and enrichment of bafilomycin A1 (baf A1) from a crude extract of the marine microorganism Streptomyces lohii fermentation. This strategy comprises liquid−liquid extraction (LLE) with a three-phase solvent system (n-hexane–ethyl acetate–acetonitrile–water = [...] Read more.

An efficient strategy was developed for the rapid separation and enrichment of bafilomycin A1 (baf A1) from a crude extract of the marine microorganism Streptomyces lohii fermentation. This strategy comprises liquid−liquid extraction (LLE) with a three-phase solvent system (n-hexane–ethyl acetate–acetonitrile–water = 7:3:5:5, v/v/v/v) followed by separation using high-speed counter-current chromatography (HSCCC). The results showed that a 480.2-mg fraction of baf A1-enriched extract in the middle phase of the three-phase solvent system was prepared from 4.9 g of crude extract after two consecutive one-step operations. Over 99% of soybean oil, the main hydrophobic waste in the crude extract, and the majority of hydrophilic impurities were distributed in the upper and lower phase, respectively. HSCCC was used with a two-phase solvent system composed of n-hexane–acetonitrile–water (15:8:12, v/v/v) to isolate and purify baf A1 from the middle phase fraction, which yielded 77.4 mg of baf A1 with > 95% purity within 90 min. The overall recovery of baf A1 in the process was determined to be 95.7%. The use of a three-phase solvent system represents a novel strategy for the simultaneous removal of hydrophobic oil and hydrophilic impurities from a microbial fermentation extract. Full article

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21 pages, 953 KiB

Open AccessArticle

LC-ESI-QTOF-MS/MS Characterization of Seaweed Phenolics and Their Antioxidant Potential

by Biming Zhong, Nicholas A. Robinson, Robyn D. Warner, Colin J. Barrow, Frank R. Dunshea and Hafiz A.R. Suleria

Mar. Drugs 2020, 18(6), 331; https://doi.org/10.3390/md18060331 - 24 Jun 2020

Cited by 90 | Viewed by 8259

Abstract

Seaweed is an important food widely consumed in Asian countries. Seaweed has a diverse array of bioactive compounds, including dietary fiber, carbohydrate, protein, fatty acid, minerals and polyphenols, which contribute to the health benefits and commercial value of seaweed. Nevertheless, detailed information on [...] Read more.

Seaweed is an important food widely consumed in Asian countries. Seaweed has a diverse array of bioactive compounds, including dietary fiber, carbohydrate, protein, fatty acid, minerals and polyphenols, which contribute to the health benefits and commercial value of seaweed. Nevertheless, detailed information on polyphenol content in seaweeds is still limited. Therefore, the present work aimed to investigate the phenolic compounds present in eight seaweeds [Chlorophyta (green), Ulva sp., Caulerpa sp. and Codium sp.; Rhodophyta (red), Dasya sp., Grateloupia sp. and Centroceras sp.; Ochrophyta (brown), Ecklonia sp., Sargassum sp.], using liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS). The total phenolic content (TPC), total flavonoid content (TFC) and total tannin content (TTC) were determined. The antioxidant potential of seaweed was assessed using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, a 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging assay and a ferric reducing antioxidant power (FRAP) assay. Brown seaweed species showed the highest total polyphenol content, which correlated with the highest antioxidant potential. The LC-ESI-QTOF-MS/MS tentatively identified a total of 54 phenolic compounds present in the eight seaweeds. The largest number of phenolic compounds were present in Centroceras sp. followed by Ecklonia sp. and Caulerpa sp. Using high-performance liquid chromatography-photodiode array (HPLC-PDA) quantification, the most abundant phenolic compound was p-hydroxybenzoic acid, present in Ulva sp. at 846.083 ± 0.02 μg/g fresh weight. The results obtained indicate the importance of seaweed as a promising source of polyphenols with antioxidant properties, consistent with the health potential of seaweed in food, pharmaceutical and nutraceutical applications. Full article

(This article belongs to the Special Issue Marine Phenolics: Extraction and Purification, Identification, Characterization and Applications)

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22 pages, 7925 KiB

Open AccessFeature PaperArticle

The Advanced Floating Chirality Distance Geometry Approach―How Anisotropic NMR Parameters Can Support the Determination of the Relative Configuration of Natural Products

by Matthias Köck, Michael Reggelin and Stefan Immel

Mar. Drugs 2020, 18(6), 330; https://doi.org/10.3390/md18060330 - 24 Jun 2020

Cited by 7 | Viewed by 3025

Abstract

The configurational analysis of complex natural products by NMR spectroscopy is still a challenging task. The assignment of the relative configuration is usually carried out by analysis of interproton distances from NOESY or ROESY spectra (qualitative or quantitative) and scalar (J) [...] Read more.

The configurational analysis of complex natural products by NMR spectroscopy is still a challenging task. The assignment of the relative configuration is usually carried out by analysis of interproton distances from NOESY or ROESY spectra (qualitative or quantitative) and scalar (J) couplings. About 15 years ago, residual dipolar couplings (RDCs) were introduced as a tool for the configurational determination of small organic molecules. In contrast to NOEs/ROEs which are local parameters (distances up to 400 pm can be detected for small organic molecules), RDCs are global parameters which allow to obtain structural information also from long-range relationships. RDCs have the disadvantage that the sample needs a setup in an alignment medium in order to obtain the required anisotropic environment. Here, we will discuss the configurational analysis of five complex natural products: axinellamine A (1), tetrabromostyloguanidine (2), 3,7-epi-massadine chloride (3), tubocurarine (4), and vincristine (5). Compounds 1–3 are marine natural products whereas 4 and 5 are from terrestrial sources. The chosen examples will carefully work out the limitations of NOEs/ROEs in the configurational analysis of natural products and will also provide an outlook on the information obtained from RDCs. Full article

(This article belongs to the Special Issue Selected Papers from XVI MaNaPro and XI ECMNP)

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43 pages, 6690 KiB

Open AccessReview

Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects

by Rajiv Dahiya, Sunita Dahiya, Neeraj Kumar Fuloria, Suresh Kumar, Rita Mourya, Suresh V. Chennupati, Satish Jankie, Hemendra Gautam, Sunil Singh, Sanjay Kumar Karan, Sandeep Maharaj, Shivkanya Fuloria, Jyoti Shrivastava, Alka Agarwal, Shamjeet Singh, Awadh Kishor, Gunjan Jadon and Ajay Sharma

Mar. Drugs 2020, 18(6), 329; https://doi.org/10.3390/md18060329 - 24 Jun 2020

Cited by 30 | Viewed by 5150

Abstract

Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a [...] Read more.

Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide–peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents. Full article

(This article belongs to the Special Issue Bioactive Marine Heterocyclic Compounds)

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17 pages, 7573 KiB

Open AccessArticle

Fucoidan Isolated from Saccharina japonica Inhibits LPS-Induced Inflammation in Macrophages via Blocking NF-κB, MAPK and JAK-STAT Pathways

by Jing Ye, Donghui Chen, Zhicheng Ye, Yayan Huang, Na Zhang, Edmund M. K. Lui, Changhu Xue and Meitian Xiao

Mar. Drugs 2020, 18(6), 328; https://doi.org/10.3390/md18060328 - 24 Jun 2020

Cited by 33 | Viewed by 3421

Abstract

Fucoidan has been reported to have a variety of biological activities. However, different algae species, extraction methods, harvesting seasons, and growth regions lead to the structural variation of fucoidan, which would affect the bioactivities of fucoidan. To date, the anti-inflammatory properties and the [...] Read more.

Fucoidan has been reported to have a variety of biological activities. However, different algae species, extraction methods, harvesting seasons, and growth regions lead to the structural variation of fucoidan, which would affect the bioactivities of fucoidan. To date, the anti-inflammatory properties and the underlying mechanism of fucoidan from brown alga Saccharina japonica (S. japonica) remain limited. The aims of the present study were to investigate the structure, the anti-inflammatory properties, and the potential molecular mechanisms of fucoidan isolated from S. japonica (SF6) against lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. SF6 was characterized using high performance liquid gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR), and observed to be rich in fucose, galactose, and sulfate. Additionally, results showed that SF6 remarkably inhibited LPS-induced production of various inflammatory mediators and pro-inflammation cytokines, including nitric oxide (NO), NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-β (IL-β), and interleukin-6 (IL-6). A mechanism study showed that SF6 could effectively inhibit inflammatory responses through blocking LPS-induced inflammation pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase (JAK)-2 and signal transducer and activator of transcription (STAT)-1/3 pathways. These results suggested that SF6 has the potential to be developed as an anti-inflammatory agent applied in functional food. Full article

(This article belongs to the Special Issue Seaweeds Secondary Metabolites: Successes In and/or Probable Therapeutic Applications 2.0)

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14 pages, 3294 KiB

Open AccessArticle

Bioactivity of Spongian Diterpenoid Scaffolds from the Antarctic Sponge Dendrilla antarctica

by Alexandre Bory, Andrew J. Shilling, Jessie Allen, Ala Azhari, Alison Roth, Lindsey N. Shaw, Dennis E. Kyle, John H. Adams, Charles D. Amsler, James B. McClintock and Bill J. Baker

Mar. Drugs 2020, 18(6), 327; https://doi.org/10.3390/md18060327 - 23 Jun 2020

Cited by 17 | Viewed by 3966

Abstract

The Antarctic sponge Dendrilla antarctica is rich in defensive terpenoids with promising antimicrobial potential. Investigation of this demosponge has resulted in the generation of a small chemical library containing diterpenoid secondary metabolites with bioactivity in an infectious disease screening campaign focused on Leishmania [...] Read more.

The Antarctic sponge Dendrilla antarctica is rich in defensive terpenoids with promising antimicrobial potential. Investigation of this demosponge has resulted in the generation of a small chemical library containing diterpenoid secondary metabolites with bioactivity in an infectious disease screening campaign focused on Leishmania donovani, Plasmodium falciparum, and methicillin-resistant Staphylococcus aureus (MRSA) biofilm. In total, eleven natural products were isolated, including three new compounds designated dendrillins B–D (10–12). Chemical modification of abundant natural products led to three semisynthetic derivatives (13–15), which were also screened. Several compounds showed potency against the leishmaniasis parasite, with the natural products tetrahydroaplysulphurin-1 (4) and dendrillin B (10), as well as the semisynthetic triol 15, displaying single-digit micromolar activity and low mammalian cytotoxicity. Triol 15 displayed the best profile against the liver-stage malaria parasites, while membranolide (5) and dendrillin C (11) were strong hits against MRSA biofilm cultures. Full article

(This article belongs to the Special Issue Structure–Activity Relationship of Marine Bioactive Compounds)

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15 pages, 1326 KiB

Open AccessArticle

In Vitro and In Vivo Assessment of the Efficacy of Bromoageliferin, an Alkaloid Isolated from the Sponge Agelas dilatata, against Pseudomonas aeruginosa

by Dawrin Pech-Puch, Mar Pérez-Povedano, Marta Martinez-Guitian, Cristina Lasarte-Monterrubio, Juan Carlos Vázquez-Ucha, Germán Bou, Jaime Rodríguez, Alejandro Beceiro and Carlos Jimenez

Mar. Drugs 2020, 18(6), 326; https://doi.org/10.3390/md18060326 - 23 Jun 2020

Cited by 19 | Viewed by 3091

Abstract

The pyrrole-imidazoles, a group of alkaloids commonly found in marine sponges belonging to the genus Agelas, display a wide range of biological activities. Herein, we report the first chemical study of the secondary metabolites of the sponge A. dilatata from the coastal [...] Read more.

The pyrrole-imidazoles, a group of alkaloids commonly found in marine sponges belonging to the genus Agelas, display a wide range of biological activities. Herein, we report the first chemical study of the secondary metabolites of the sponge A. dilatata from the coastal area of the Yucatan Peninsula (Mexico). In this study, we isolated eight known alkaloids from an organic extract of the sponge. We used NMR and MS analysis and comparison with existing databases to characterize the alkaloids: ageliferin (1), bromoageliferin (2), dibromoageliferin (3), sceptrin (4), nakamuric acid (5), 4-bromo-1H-pyrrole-2-carboxylic acid (6), 4,5-dibromopyrrole-2-carboxylic acid (7) and 3,7-dimethylisoguanine (8). We also evaluated, for the first time, the activity of these alkaloids against the most problematic multidrug-resistant (MDR) pathogens, i.e., the Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Bromoageliferin (2) displayed significant activity against P. aeruginosa. Comparison of the antibacterial activity of ageliferins 1–3 (of similar structure) against P. aeruginosa revealed some relationship between structure and activity. Furthermore, in in vitro assays, 2 inhibited growth and biofilm production in clinical strains of P. aeruginosa. Moreover, 2 increased the survival time in an in vivo Galleria mellonella model of infection. The findings confirm bromoageliferin (2) as a potential lead for designing new antibacterial drugs. Full article

(This article belongs to the Special Issue Structure–Activity Relationship of Marine Bioactive Compounds)

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11 pages, 2852 KiB

Open AccessArticle

Fabrication of 3D-Printed Fish-Gelatin-Based Polymer Hydrogel Patches for Local Delivery of PEGylated Liposomal Doxorubicin

by Jin Liu, Tatsuaki Tagami and Tetsuya Ozeki

Mar. Drugs 2020, 18(6), 325; https://doi.org/10.3390/md18060325 - 20 Jun 2020

Cited by 47 | Viewed by 7348

Abstract

3D printing technology has been applied to various fields and its medical applications are expanding. Here, we fabricated implantable 3D bio-printed hydrogel patches containing a nanomedicine as a future tailored cancer treatment. The patches were prepared using a semi-solid extrusion-type 3D bioprinter, a [...] Read more.

3D printing technology has been applied to various fields and its medical applications are expanding. Here, we fabricated implantable 3D bio-printed hydrogel patches containing a nanomedicine as a future tailored cancer treatment. The patches were prepared using a semi-solid extrusion-type 3D bioprinter, a hydrogel-based printer ink, and UV-LED exposure. We focused on the composition of the printer ink and semi-synthesized fish gelatin methacryloyl (F-GelMA), derived from cold fish gelatin, as the main component. The low viscosity of F-GelMA due to its low melting point was remarkably improved by the addition of carboxymethyl cellulose sodium (CMC), a pharmaceutical excipient. PEGylated liposomal doxorubicin (DOX), as a model nanomedicine, was incorporated into the hydrogel and liposome stability after photo-polymerization was evaluated. The addition of CMC inhibited particle size increase. Three types of 3D-designed patches (cylinder, torus, gridlines) were produced using a 3D bioprinter. Drug release was dependent on the shape of the 3D-printed patches and UV-LED exposure time. The current study provides useful information for the preparation of 3D printed nanomedicine-based objects. Full article

(This article belongs to the Special Issue Nano-Marine Drugs: Relevance of Nanoformulations in Cancer Therapies)

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10 pages, 962 KiB

Open AccessArticle

Aromatic Polyketides from a Symbiotic Strain Aspergillus fumigatus D and Characterization of Their Biosynthetic Gene D8.t287

by Yi Hua, Rui Pan, Xuelian Bai, Bin Wei, Jianwei Chen, Hong Wang and Huawei Zhang

Mar. Drugs 2020, 18(6), 324; https://doi.org/10.3390/md18060324 - 20 Jun 2020

Cited by 12 | Viewed by 3823

Abstract

The chemical investigation of one symbiotic strain, Aspergillus fumigatus D, from the coastal plant Edgeworthia chrysantha Lindl led to the isolation of eight compounds (1–8), which were respectively identified as rubrofusarin B (1), alternariol 9-O-methyl [...] Read more.

The chemical investigation of one symbiotic strain, Aspergillus fumigatus D, from the coastal plant Edgeworthia chrysantha Lindl led to the isolation of eight compounds (1–8), which were respectively identified as rubrofusarin B (1), alternariol 9-O-methyl ether (2), fonsecinone D (3), asperpyrone A (4), asperpyrone D (5), fonsecinone B (6), fonsecinone A (7), and aurasperone A (8) by a combination of spectroscopic methods (1D NMR and ESI-MS) as well as by comparison with the literature data. An antimicrobial assay showed that these aromatic polyketides exhibited no remarkable inhibitory effect on Escherichia coli, Staphyloccocus aureus and Candida albicans. The genomic feature of strain D was analyzed, as well as its biosynthetic gene clusters, using antibiotics and Secondary Metabolite Analysis Shell 5.1.2 (antiSMASH). Plausible biosynthetic pathways for dimeric naphtho-γ-pyrones 3–8 were first proposed in this work. A non-reducing polyketide synthase (PKS) gene D8.t287 responsible for the biosynthesis of these aromatic polyketides 1–8 was identified and characterized by target gene knockout experiment and UPLC-MS analysis. Full article

(This article belongs to the Special Issue Aromatic Marine Natural Products: Chemistry and Bioactivity)

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33 pages, 1827 KiB

Open AccessReview

Algae Metabolites in Cosmeceutical: An Overview of Current Applications and Challenges

by Krishnapriya Thiyagarasaiyar, Bey-Hing Goh, You-Jin Jeon and Yoon-Yen Yow

Mar. Drugs 2020, 18(6), 323; https://doi.org/10.3390/md18060323 - 19 Jun 2020

Cited by 72 | Viewed by 11593

Abstract

Cosmetics are widely used by people around the world to protect the skin from external stimuli. Consumer preference towards natural cosmetic products has increased as the synthetic cosmetic products caused adverse side effects and resulted in low absorption rate due to the chemicals’ [...] Read more.

Cosmetics are widely used by people around the world to protect the skin from external stimuli. Consumer preference towards natural cosmetic products has increased as the synthetic cosmetic products caused adverse side effects and resulted in low absorption rate due to the chemicals’ larger molecular size. The cosmetic industry uses the term “cosmeceutical”, referring to a cosmetic product that is claimed to have medicinal or drug-like benefits. Marine algae have gained tremendous attention in cosmeceuticals. They are one of the richest marine resources considered safe and possessed negligible cytotoxicity effects on humans. Marine algae are rich in bioactive substances that have shown to exhibit strong benefits to the skin, particularly in overcoming rashes, pigmentation, aging, and cancer. The current review provides a detailed survey of the literature on cosmeceutical potentials and applications of algae as skin whitening, anti-aging, anticancer, antioxidant, anti-inflammation, and antimicrobial agents. The biological functions of algae and the underlying mechanisms of all these activities are included in this review. In addition, the challenges of using algae in cosmeceutical applications, such as the effectiveness of different extraction methods and processing, quality assurance, and regulations concerning extracts of algae in this sector were also discussed. Full article

(This article belongs to the Special Issue Marine-Derived Ingredients for Cosmeceuticals)

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16 pages, 2871 KiB

Open AccessReview

Phycocosmetics and Other Marine Cosmetics, Specific Cosmetics Formulated Using Marine Resources

by Céline Couteau and Laurence Coiffard

Mar. Drugs 2020, 18(6), 322; https://doi.org/10.3390/md18060322 - 18 Jun 2020

Cited by 19 | Viewed by 5807

Abstract

Marine resources exist in vast numbers and show enormous diversity. As a result, there are likely many possible applications for marine molecules of interest in the cosmetic industry, whether as excipients or additives, but especially as active substances. It is possible to obtain [...] Read more.

Marine resources exist in vast numbers and show enormous diversity. As a result, there are likely many possible applications for marine molecules of interest in the cosmetic industry, whether as excipients or additives, but especially as active substances. It is possible to obtain extracts from active substances; for example, quite a few algae species can be used in moisturizing or anti-ageing products. In the field of topical photoprotection, mycosporine-like amino acids and gadusol are important lines of enquiry that should not be overlooked. In the field of additives, the demonstration that certain seaweed (algae) extracts have antimicrobial properties suggests that they could provide alternatives to currently authorized preservatives. These promising leads must be explored, but it should be kept in mind that it is a long process to bring ingredients to market that are both effective and safe to use. Full article

(This article belongs to the Special Issue Marine-Derived Ingredients for Cosmeceuticals)

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48 pages, 6411 KiB

Open AccessFeature PaperReview

A Review of Terpenes from Marine-Derived Fungi: 2015–2019

by Minghua Jiang, Zhenger Wu, Heng Guo, Lan Liu and Senhua Chen

Mar. Drugs 2020, 18(6), 321; https://doi.org/10.3390/md18060321 - 18 Jun 2020

Cited by 46 | Viewed by 5762

Abstract

Marine-derived fungi are a significant source of pharmacologically active metabolites with interesting structural properties, especially terpenoids with biological and chemical diversity. In the past five years, there has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered. [...] Read more.

Marine-derived fungi are a significant source of pharmacologically active metabolites with interesting structural properties, especially terpenoids with biological and chemical diversity. In the past five years, there has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered. In this updated review, we examine the chemical structures and bioactive properties of new terpenes from marine-derived fungi, and the biodiversity of these fungi from 2015 to 2019. A total of 140 research papers describing 471 new terpenoids of six groups (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and meroterpenes) from 133 marine fungal strains belonging to 34 genera were included. Among them, sesquiterpenes, meroterpenes, and diterpenes comprise the largest proportions of terpenes, and the fungi genera of Penicillium, Aspergillus, and Trichoderma are the dominant producers of terpenoids. The majority of the marine-derived fungi are isolated from live marine matter: marine animals and aquatic plants (including mangrove plants and algae). Moreover, many terpenoids display various bioactivities, including cytotoxicity, antibacterial activity, lethal toxicity, anti-inflammatory activity, enzyme inhibitor activity, etc. In our opinion, the chemical diversity and biological activities of these novel terpenoids will provide medical and chemical researchers with a plenty variety of promising lead compounds for the development of marine drugs. Full article

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9 pages, 1131 KiB

Open AccessArticle

Halosmysin A, a Novel 14-Membered Macrodiolide Isolated from the Marine-Algae-Derived Fungus Halosphaeriaceae sp.

by Takeshi Yamada, Haruka Kogure, Minami Kataoka, Takashi Kikuchi and Tomoya Hirano

Mar. Drugs 2020, 18(6), 320; https://doi.org/10.3390/md18060320 - 18 Jun 2020

Cited by 14 | Viewed by 2443

Abstract

Halosmysin A, a new 14-membered macrodiolide with an unprecedented skeleton, was isolated from the fungus Halosphaeriaceae sp. OUPS-135D-4, which, in turn, was obtained from the marine algae Sargassum thunbergii. The chemical structure of the macrodiolide was elucidated using 1D and 2D NMR, as [...] Read more.

Halosmysin A, a new 14-membered macrodiolide with an unprecedented skeleton, was isolated from the fungus Halosphaeriaceae sp. OUPS-135D-4, which, in turn, was obtained from the marine algae Sargassum thunbergii. The chemical structure of the macrodiolide was elucidated using 1D and 2D NMR, as well as high resolution fast atom bombardment mass (HRFABMS) spectral analysis. The absolute stereochemistry was determined via chemical derivatization and comparison with a known compound, (6R,11R,12R,14R)-colletodiol. Additionally, halosmysin A was shown to be very potent against murine P388 leukemia, human HL-60 leukemia, and murine L1210 leukemia cell lines, with IC₅₀ values ranging from 2.2 ± 3.1 to 11.7 ± 2.8 μM. Full article

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15 pages, 2795 KiB

Open AccessArticle

Partial Characterization of Protease Inhibitors of Ulva ohnoi and Their Effect on Digestive Proteases of Marine Fish

by Antonio Jesús Vizcaíno, Alba Galafat, María Isabel Sáez, Tomás Francisco Martínez and Francisco Javier Alarcón

Mar. Drugs 2020, 18(6), 319; https://doi.org/10.3390/md18060319 - 18 Jun 2020

Cited by 13 | Viewed by 3112

Abstract

This piece of research evaluates the presence of protease inhibitors in the macroalga Ulva ohnoi and provides an initial overview of their mode of action. The ability of Ulva protease inhibitors to inhibit digestive proteases of three marine fish species, as well as [...] Read more.

This piece of research evaluates the presence of protease inhibitors in the macroalga Ulva ohnoi and provides an initial overview of their mode of action. The ability of Ulva protease inhibitors to inhibit digestive proteases of three marine fish species, as well as their capacity to hamper the hydrolysis of a reference protein by those fish proteases, were assessed. In addition, thermal stability and the mode of inhibition on trypsin and chymotrypsin were also studied. Dose-response inhibition curves and in vitro protein hydrolysis assays revealed a noticeable inhibition of fish enzymes when Ulva concentration increased in the assay. The thermal treatment of Ulva reduced markedly the inhibitory effect on fish digestive protease. Finally, Lineweaver–Burk plots indicated that trypsin and chymotrypsin inhibition consisted of a mixed-type inhibition mechanism in which the inhibitory effect depends on Ulva concentration. Overall, the results confirmed the presence of protease inhibitors in Ulva, though heat treatment was enough for inactivating these compounds. Full article

(This article belongs to the Special Issue Enzyme Inhibitor from Marine Organisms)

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14 pages, 1026 KiB

Open AccessArticle

Effects of Fish Oil and Grape Seed Extract Combination on Hepatic Endogenous Antioxidants and Bioactive Lipids in Diet-Induced Early Stages of Insulin Resistance in Rats

by Núria Taltavull, Bernat Miralles-Pérez, Maria Rosa Nogués, Sara Ramos-Romero, Lucía Méndez, Isabel Medina, Josep Lluís Torres and Marta Romeu

Mar. Drugs 2020, 18(6), 318; https://doi.org/10.3390/md18060318 - 16 Jun 2020

Cited by 9 | Viewed by 3477

Abstract

Diacylglycerols (DAG) and ceramides have been suggested as early predictors of insulin resistance. This study was aimed to examine the combined effects of fish oil (FO) and grape seed extract (GSE) on hepatic endogenous antioxidants, DAG and ceramides in diet-induced early stages of [...] Read more.

Diacylglycerols (DAG) and ceramides have been suggested as early predictors of insulin resistance. This study was aimed to examine the combined effects of fish oil (FO) and grape seed extract (GSE) on hepatic endogenous antioxidants, DAG and ceramides in diet-induced early stages of insulin resistance. Thirty-five rats were fed one of the following diets: (1) a standard diet (STD group), (2) a high-fat high-sucrose diet (HFHS group), (3) an HFHS diet enriched with FO (FO group), (4) an HFHS diet enriched with GSE (GSE group) or (5) an HFHS diet enriched with FO and GSE (FO + GSE group). In the liver, endogenous antioxidants were measured using spectrophotometric and fluorometric techniques, and non-targeted lipidomics was conducted for the assessment of DAG and ceramides. After 24 weeks, the FO + GSE group showed increased glutathione peroxidase activity, as well as monounsaturated fatty acid and polyunsaturated fatty acid-containing DAG, and long-chain fatty acid-containing ceramides abundances compared to the STD group. The FO and GSE combination induced similar activation of the antioxidant system and bioactive lipid accumulation in the liver than the HFHS diet without supplementation. In addition, the FO and GSE combination increased the abundances of polyunsaturated fatty acid-containing DAG in the liver. Full article

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32 pages, 13318 KiB

Open AccessReview

Chemical Diversity and Biological Activities of Meroterpenoids from Marine Derived-Fungi: A Comprehensive Update

by Amr El-Demerdash, Decha Kumla and Anake Kijjoa

Mar. Drugs 2020, 18(6), 317; https://doi.org/10.3390/md18060317 - 15 Jun 2020

Cited by 25 | Viewed by 4481

Abstract

Meroterpenoids are a class of hybrid natural products, partially derived from a mixed terpenoid pathway. They possess remarkable structural features and relevant biological and pharmacological activities. Marine-derived fungi are a rich source of meroterpenoids featuring structural diversity varying from simple to complex molecular [...] Read more.

Meroterpenoids are a class of hybrid natural products, partially derived from a mixed terpenoid pathway. They possess remarkable structural features and relevant biological and pharmacological activities. Marine-derived fungi are a rich source of meroterpenoids featuring structural diversity varying from simple to complex molecular architectures. A combination of a structural variability and their myriad of bioactivities makes meroterpenoids an interesting class of naturally occurring compounds for chemical and pharmacological investigation. In this review, a comprehensive literature survey covering the period of 2009–2019, with 86 references, is presented focusing on chemistry and biological activities of various classes of meroterpenoids isolated from fungi obtained from different marine hosts and environments. Full article

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12 pages, 2181 KiB

Open AccessArticle

Protective Effect of a Fucose-Rich Fucoidan Isolated from Saccharina japonica against Ultraviolet B-Induced Photodamage In Vitro in Human Keratinocytes and In Vivo in Zebrafish

by Wanchun Su, Lei Wang, Xiaoting Fu, Liying Ni, Delin Duan, Jiachao Xu and Xin Gao

Mar. Drugs 2020, 18(6), 316; https://doi.org/10.3390/md18060316 - 15 Jun 2020

Cited by 24 | Viewed by 3809

Abstract

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT [...] Read more.

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry. Full article

(This article belongs to the Special Issue Fucoidans)

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17 pages, 2007 KiB

Open AccessArticle

Characteristics, Cryoprotection Evaluation and In Vitro Release of BSA-Loaded Chitosan Nanoparticles

by Qinying Yan, Jiaqi Weng, Xieqi Wu, Weiwei Wang, Qingliang Yang, Fangyuan Guo, Danjun Wu, Ying Song, Fan Chen and Gensheng Yang

Mar. Drugs 2020, 18(6), 315; https://doi.org/10.3390/md18060315 - 15 Jun 2020

Cited by 14 | Viewed by 3023

Abstract

Chitosan nanoparticles (CS-NPs) are under increasing investigation for the delivery of therapeutic proteins, such as vaccines, interferons, and biologics. A large number of studies have been taken on the characteristics of CS-NPs, and very few of these studies have focused on the microstructure [...] Read more.

Chitosan nanoparticles (CS-NPs) are under increasing investigation for the delivery of therapeutic proteins, such as vaccines, interferons, and biologics. A large number of studies have been taken on the characteristics of CS-NPs, and very few of these studies have focused on the microstructure of protein-loaded NPs. In this study, we prepared the CS-NPs by an ionic gelation method, and bovine serum albumin (BSA) was used as a model protein. Dynamic high pressure microfluidization (DHPM) was utilized to post-treat the nanoparticles so as to improve the uniformity, repeatability and controllability. The BSA-loaded NPs were then characterized for particle size, Zeta potential, morphology, encapsulation efficiency (EE), loading capacity (LC), and subsequent release kinetics. To improve the long-term stability of NPs, trehalose, glucose, sucrose, and mannitol were selected respectively to investigate the performance as a cryoprotectant. Furthermore, trehalose was used to obtain re-dispersible lyophilized NPs that can significantly reduce the dosage of cryoprotectants. Multiple spectroscopic techniques were used to characterize BSA-loaded NPs, in order to explain the release process of the NPs in vitro. The experimental results indicated that CS and Tripolyphosphate pentasodium (TPP) spontaneously formed the basic skeleton of the NPs through electrostatic interactions. BSA was incorporated in the basic skeleton, adsorbed on the surface of the NPs (some of which were inlaid on the NPs), without any change in structure and function. The release profiles of the NPs showed high consistency with the multispectral results. Full article

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12 pages, 4482 KiB

Open AccessArticle

Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma

by Yu-Jen Wu, Wen-Chi Wei, Guo-Fong Dai, Jui-Hsin Su, Yu-Hwei Tseng and Tsung-Chang Tsai

Mar. Drugs 2020, 18(6), 314; https://doi.org/10.3390/md18060314 - 15 Jun 2020

Cited by 11 | Viewed by 2597

Abstract

Hepatocellular carcinoma (HCC) is the most common liver or hepatic cancer, accounting for 80% of all cases. The majority of this cancer mortality is due to metastases, rather than orthotopic tumors. Therefore, the inhibition of tumor metastasis is widely recognized as the key [...] Read more.

Hepatocellular carcinoma (HCC) is the most common liver or hepatic cancer, accounting for 80% of all cases. The majority of this cancer mortality is due to metastases, rather than orthotopic tumors. Therefore, the inhibition of tumor metastasis is widely recognized as the key strategy for successful intervention. A cembrane-type diterpene, flaccidoxide-13-acetate, isolated from marine soft coral Sinularia gibberosa, has been reported to have inhibitory effects against RT4 and T24 human bladder cancer invasion and cell migration. In this study, we investigated its suppression effects on tumor growth and metastasis of human HCC, conducting Boyden chamber and Transwell assays using HA22T and HepG2 human HCC cell lines to evaluate invasion and cell migration. We utilized gelatin zymography to determine the enzyme activities of matrix metalloproteinases MMP-2 and MMP-9. We also analyzed the expression levels of MMP-2 and MMP-9. Additionally, assays of tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), the focal adhesion kinase (FAK)/phosphatidylinositide-3 kinases (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway, and the epithelial-mesenchymal transition (EMT) process were performed. We observed that flaccidoxide-13-acetate could potentially inhibit HCC cell migration and invasion. We postulated that, by inhibiting the FAK/PI3K/Akt/mTOR signaling pathway, MMP-2 and MMP-9 expressions were suppressed, resulting in HCC cell metastasis. Flaccidoxide-13-acetate was found to inhibit EMT in HA22T and HepG2 HCC cells. Our study results suggested the potential of flaccidoxide-13-acetate as a chemotherapeutic candidate; however, its clinical application for the management of HCC in humans requires further research. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)

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18 pages, 2226 KiB

Open AccessArticle

A Metabolomics Exploration of the Sexual Phase in the Marine Diatom Pseudo-nitzschia multistriata

by Federica Fiorini, Camilla Borgonuovo, Maria Immacolata Ferrante and Mark Brönstrup

Mar. Drugs 2020, 18(6), 313; https://doi.org/10.3390/md18060313 - 14 Jun 2020

Cited by 16 | Viewed by 3276

Abstract

Pseudo-nitzschia multistriata is a planktonic marine diatom with a diplontic life cycle comprising a short sexual phase, during which gametes are produced following the encounter of two diploid cells of opposite mating type (MT). Gene expression studies have highlighted the presence of substantial [...] Read more.

Pseudo-nitzschia multistriata is a planktonic marine diatom with a diplontic life cycle comprising a short sexual phase, during which gametes are produced following the encounter of two diploid cells of opposite mating type (MT). Gene expression studies have highlighted the presence of substantial changes occurring at the onset of sexual reproduction. Herein, we have hypothesized that the amount and nature of cellular metabolites varies along the mating process. To capture the metabolome of Pseudo-nitzschia multistriata at different harvesting times in an unbiased manner, we undertook an untargeted metabolomics approach based on liquid chromatography–tandem mass spectrometry. Using three different extraction steps, the method revealed pronounced differences in the metabolic profiles between control cells in the vegetative phase (MT+ and MT−) and mixed strains of opposite MTs (cross) undergoing sexual reproduction. Of the 2408 high-quality features obtained, 70 known metabolites could be identified based on in-house libraries and online databases; additional 46 features could be classified by molecular networking of tandem mass spectra. The reduction of phytol detected in the cross can be linked to the general downregulation of photosynthesis during sexual reproduction observed elsewhere. Moreover, the role of highly regulated compounds such as 7-dehydrodesmosterol, whose changes in abundance were the highest in the experiment, oleamide, ectoine, or trigonelline is discussed. Full article

(This article belongs to the Special Issue Advanced Mass Spectrometry in the Chemistry and Biology of Bioactive Marine Natural Products)

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13 pages, 2789 KiB

Open AccessFeature PaperArticle

Cloning and Characterization of a New β-Galactosidase from Alteromonas sp. QD01 and Its Potential in Synthesis of Galacto-Oligosaccharides

by Dandan Li, Shangyong Li, Yanhong Wu, Mengfei Jin, Yu Zhou, Yanan Wang, Xuehong Chen and Yantao Han

Mar. Drugs 2020, 18(6), 312; https://doi.org/10.3390/md18060312 - 14 Jun 2020

Cited by 17 | Viewed by 3975

Abstract

As prebiotics, galacto-oligosaccharides (GOSs) can improve the intestinal flora and have important applications in medicine. β-galactosidases could promote the synthesis of GOSs in lactose and catalyze the hydrolysis of lactose. In this study, a new β-galactosidase gene (gal2A), which belongs to [...] Read more.

As prebiotics, galacto-oligosaccharides (GOSs) can improve the intestinal flora and have important applications in medicine. β-galactosidases could promote the synthesis of GOSs in lactose and catalyze the hydrolysis of lactose. In this study, a new β-galactosidase gene (gal2A), which belongs to the glycoside hydrolase family 2, was cloned from marine bacterium Alteromonas sp. QD01 and expressed in Escherichia coli. The molecular weight of Gal2A was 117.07 kDa. The optimal pH and temperature of Gal2A were 8.0 and 40 °C, respectively. At the same time, Gal2A showed wide pH stability in the pH range of 6.0–9.5, which is suitable for lactose hydrolysis in milk. Most metal ions promoted the activity of Gal2A, especially Mn²⁺ and Mg²⁺. Importantly, Gal2A exhibited high transglycosylation activity, which can catalyze the formation of GOS from milk and lactose. These characteristics indicated that Gal2A may be ideal for producing GOSs and lactose-reducing dairy products. Full article

(This article belongs to the Special Issue Carbohydrate-Containing Marine Compounds of Mixed Biogenesis)

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21 pages, 2024 KiB

Open AccessArticle

Bioactive Molecular Networking for Mapping the Antimicrobial Constituents of the Baltic Brown Alga Fucus vesiculosus

by Larissa Buedenbender, Francesca Anna Astone and Deniz Tasdemir

Mar. Drugs 2020, 18(6), 311; https://doi.org/10.3390/md18060311 - 13 Jun 2020

Cited by 21 | Viewed by 8758

Abstract

The brown alga Fucus vesiculosus is common to the intertidal zones of the Baltic Sea, where it is exposed to high fouling pressures by microorganisms. Our previous studies showed, repeatedly, the consistent antimicrobial activity of F. vesiculosus crude extracts against human pathogens, while [...] Read more.

The brown alga Fucus vesiculosus is common to the intertidal zones of the Baltic Sea, where it is exposed to high fouling pressures by microorganisms. Our previous studies showed, repeatedly, the consistent antimicrobial activity of F. vesiculosus crude extracts against human pathogens, while untargeted metabolomics analyses have revealed a variety of metabolites. In this study, we applied the UPLC-QToF-MS/MS-based “bioactive molecular networking” (BMN) concept on the most bioactive n-hexane and n-butanol subextracts of Baltic F. vesiculosus coupled with in silico dereplication tools to identify the compounds responsible for antimicrobial activity. The first antimicrobial cluster identified by BMN was galactolipids. Our targeted isolation efforts for this class led to the isolation of six monogalactosyldiacylglycerol (MGDG) derivatives (1–6) and one digalactosyldiacylglycerol (DGDG, 7). The MGDGs 5 and 6 and the DGDG 7 exhibited activity against Staphylococcus aureus. The second compound class with high bioactivity was phlorotannins. In particular, phlorethol-type phlorotannins showed high correlations with antimicrobial activity based on the BMN approach, and two phlorotannins (8–9) were isolated. This study shows that antimicrobial components of F. vesiculosus reside in the algal cell walls and membranes and that BMN provides a complementary tool for the targeted isolation of bioactive metabolites. Full article

(This article belongs to the Special Issue Molecular Networking as a Strategy in Discovery of Marine Bioactive Compounds)

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11 pages, 1420 KiB

Open AccessArticle

Leptogorgins A–C, Humulane Sesquiterpenoids from the Vietnamese Gorgonian Leptogorgia sp.

by Irina I. Kapustina, Tatyana N. Makarieva, Alla G. Guzii, Anatoly I. Kalinovsky, Roman S. Popov, Sergey A. Dyshlovoy, Boris B. Grebnev, Gunhild von Amsberg and Valentin A. Stonik

Mar. Drugs 2020, 18(6), 310; https://doi.org/10.3390/md18060310 - 13 Jun 2020

Cited by 6 | Viewed by 2447

Abstract

Leptogorgins A–C (1–3), new humulane sesquiterpenoids, and leptogorgoid A (4), a new dihydroxyketosteroid, were isolated from the gorgonian Leptogorgia sp. collected from the South China Sea. The structures were established using MS and NMR data. The absolute [...] Read more.

Leptogorgins A–C (1–3), new humulane sesquiterpenoids, and leptogorgoid A (4), a new dihydroxyketosteroid, were isolated from the gorgonian Leptogorgia sp. collected from the South China Sea. The structures were established using MS and NMR data. The absolute configuration of 1 was confirmed by a modification of Mosher’s method. Configurations of double bonds followed from NMR data, including NOE correlations. This is the first report of humulane-type sesquiterpenoids from marine invertebrates. Sesquiterpenoids leptogorgins A (1) and B (2) exhibited a moderate cytotoxicity and some selectivity against human drug-resistant prostate cancer cells 22Rv1. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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15 pages, 1971 KiB

Open AccessFeature PaperArticle

Mussel Shell-Derived Macroporous 3D Scaffold: Characterization and Optimization Study of a Bioceramic from the Circular Economy

by Stefania Scialla, Francesca Carella, Massimiliano Dapporto, Simone Sprio, Andreana Piancastelli, Barbara Palazzo, Alessio Adamiano, Lorenzo Degli Esposti, Michele Iafisco and Clara Piccirillo

Mar. Drugs 2020, 18(6), 309; https://doi.org/10.3390/md18060309 - 12 Jun 2020

Cited by 25 | Viewed by 3796

Abstract

Fish industry by-products constitute an interesting platform for the extraction and recovery of valuable compounds in a circular economy approach. Among them, mussel shells could provide a calcium-rich source for the synthesis of hydroxyapatite (HA) bioceramics. In this work, HA nanoparticles have been [...] Read more.

Fish industry by-products constitute an interesting platform for the extraction and recovery of valuable compounds in a circular economy approach. Among them, mussel shells could provide a calcium-rich source for the synthesis of hydroxyapatite (HA) bioceramics. In this work, HA nanoparticles have been successfully synthesized starting from mussel shells (Mytilus edulis) with a two steps process based on thermal treatment to convert CaCO₃ in CaO and subsequent wet precipitation with a phosphorus source. Several parameters were studied, such as the temperature and gaseous atmosphere of the thermal treatment as well as the use of two different phosphorus-containing reagents in the wet precipitation. Data have revealed that the characteristics of the powders can be tailored, changing the conditions of the process. In particular, the use of (NH₄)₂HPO₄ as the phosphorus source led to HA nanoparticles with a high crystallinity degree, while smaller nanoparticles with a higher surface area were obtained when H₃PO₄ was employed. Further, a selected HA sample was synthesized at the pilot scale; then, it was employed to fabricate porous 3D scaffolds using the direct foaming method. A highly porous scaffold with open and interconnected porosity associated with good mechanical properties (i.e., porosity in the range 87–89%, pore size in the range 50–300 μm, and a compressive strength σ = 0.51 ± 0.14 MPa) suitable for bone replacement was achieved. These results suggest that mussel shell by-products are effectively usable for the development of compounds of high added value in the biomedical field. Full article

(This article belongs to the Special Issue Marine Organisms for Bone Regeneration - 2020)

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18 pages, 2878 KiB

Open AccessArticle

Exploring the Microalga Euglena cantabrica by Pressurized Liquid Extraction to Obtain Bioactive Compounds

by Nerea Muñóz-Almagro, Bienvenida Gilbert-López, Pozuelo-Rollón M. Carmen, Yolanda García-Fernandez, Carlos Almeida, Mar Villamiel, Jose A. Mendiola and Elena Ibáñez

Mar. Drugs 2020, 18(6), 308; https://doi.org/10.3390/md18060308 - 12 Jun 2020

Cited by 6 | Viewed by 3265

Abstract

In the present study, the chemical composition of the microalga Euglena cantabrica was investigated. The extraction of bioactive compounds was done using pressurized liquid extraction (PLE) at different temperatures (40–180 °C) and using green solvents (ethanol-water mixtures). A statistical design of experiments was [...] Read more.

In the present study, the chemical composition of the microalga Euglena cantabrica was investigated. The extraction of bioactive compounds was done using pressurized liquid extraction (PLE) at different temperatures (40–180 °C) and using green solvents (ethanol-water mixtures). A statistical design of experiments was used to optimize the maximum antioxidant capacity of the extracts by response surface methodology. The antioxidant capacity was determined through the inhibition of 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, while the chemical analyses of the extracts were carried out using different chromatographic techniques. Chlorophylls and carotenoids were analyzed by high-performance liquid chromatography coupled to a diode array detector and mass spectrometry (HPLC-DAD-MS/MS) and carbohydrates by gas chromatography with flame ionization detection (GC-FID) and high-pressure size-exclusion chromatography coupled to an evaporative light-scattering detector (HPSEC-ELSD). The results showed different possibilities for the extraction conditions, depending on the desired bioactivity or chemical composition. Briefly, (i) mixtures of ethanol-water containing around 40% ethanol at 180 °C gave the best antioxidant capacity, (ii) mixtures containing around 50% ethanol at 110 °C gave the best yield of β-glucan paramylon, and (iii) the use of pure ethanol at a low temperature (40 °C) is the best choice for the recovery of carotenoids such as diatoxanthin. Summing up, E. cantabrica seems to be a good candidate to be used in biorefinery to obtain different bioactive compounds. Full article

(This article belongs to the Special Issue Innovative Extraction Technology Aiming the Screening and Discovery of Bio-Active Marine Compounds)

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37 pages, 5809 KiB

Open AccessReview

Secondary Metabolites of the Genus Didemnum: A Comprehensive Review of Chemical Diversity and Pharmacological Properties

by Diaa T. A. Youssef, Hadeel Almagthali, Lamiaa A. Shaala and Eric W. Schmidt

Mar. Drugs 2020, 18(6), 307; https://doi.org/10.3390/md18060307 - 11 Jun 2020

Cited by 16 | Viewed by 4084

Abstract

Tunicates (ascidians) are common marine invertebrates that are an exceptionally important source of natural products with biomedical and pharmaceutical applications, including compounds that are used clinically in cancers. Among tunicates, the genus Didemnum is important because it includes the most species, and it [...] Read more.

Tunicates (ascidians) are common marine invertebrates that are an exceptionally important source of natural products with biomedical and pharmaceutical applications, including compounds that are used clinically in cancers. Among tunicates, the genus Didemnum is important because it includes the most species, and it belongs to the most speciose family (Didemnidae). The genus Didemnum includes the species D. molle, D. chartaceum, D. albopunctatum, and D. obscurum, as well as others, which are well known for their chemically diverse secondary metabolites. To date, investigators have reported secondary metabolites, usually including bioactivity data, for at least 69 members of the genus Didemnum, leading to isolation of 212 compounds. Many of these compounds exhibit valuable biological activities in assays targeting cancers, bacteria, fungi, viruses, protozoans, and the central nervous system. This review highlights compounds isolated from genus Didemnum through December 2019. Chemical diversity, pharmacological activities, geographical locations, and applied chemical methods are described. Full article

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

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23 pages, 3391 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Diversified Hamigeran B Analogs as Neuroinflammatory Inhibitors and Neurite Outgrowth Stimulators

by Ruo-Xin Li, Rui Han, Guo-Jie Wu, Fu-She Han and Jin-Ming Gao

Mar. Drugs 2020, 18(6), 306; https://doi.org/10.3390/md18060306 - 11 Jun 2020

Cited by 1 | Viewed by 2872

Abstract

We describe the efficient synthesis of a series of new simplified hamigeran B and 1-hydroxy-9-epi-hamigeran B norditerpenoid analogs (23 new members in all), structurally related to cyathane diterpenoid scaffold, and their anti-neuroinflammatory and neurite outgrowth-stimulating (neurotrophic) activity. Compounds 9a, 9h, 9o [...] Read more.

We describe the efficient synthesis of a series of new simplified hamigeran B and 1-hydroxy-9-epi-hamigeran B norditerpenoid analogs (23 new members in all), structurally related to cyathane diterpenoid scaffold, and their anti-neuroinflammatory and neurite outgrowth-stimulating (neurotrophic) activity. Compounds 9a, 9h, 9o, and 9q exhibited moderate nerve growth factor (NGF)-mediated neurite-outgrowth promoting effects in PC-12 cells at the concentration of 20 μm. Compounds 9b, 9c, 9o, 9q, and 9t showed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, of which 9c and 9q were the most potent inhibitors, with IC₅₀ values of 5.85 and 6.31 μm, respectively. Two derivatives 9q and 9o as bifunctional agents displayed good activities as NO production inhibitors and neurite outgrowth-inducers. Cytotoxicity experiments, H₂O₂-induced oxidative injury assay, and ELISA reaction speculated that compounds may inhibit the TNF-α pathway to achieve anti-inflammatory effects on nerve cells. Moreover, molecular docking studies provided a better understanding of the key structural features affecting the anti-neuroinflammatory activity and displayed significant binding interactions of some derivatives (like 9c, 9q) with the active site of iNOS protein. The structure-activity relationships (SARs) were also discussed. These results demonstrated that this structural class compounds offered an opportunity for the development of a new class of NO inhibitors and NGF-like promotors. Full article

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Mar. Drugs, Volume 18, Issue 6 (June 2020) – 57 articles

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