Marine Drugs

20 pages, 277 KiB

Open AccessReview

Beneficial Effects of Marine Algae-Derived Carbohydrates for Skin Health

by Ji Hye Kim, Jae-Eun Lee, Kyoung Heon Kim and Nam Joo Kang

Mar. Drugs 2018, 16(11), 459; https://doi.org/10.3390/md16110459 - 21 Nov 2018

Cited by 67 | Viewed by 13819

Marine algae are considered to be an abundant sources of bioactive compounds with cosmeceutical potential. Recently, a great deal of interest has focused on the health-promoting effects of marine bioactive compounds. Carbohydrates are the major and abundant constituent of marine algae and have [...] Read more.

Marine algae are considered to be an abundant sources of bioactive compounds with cosmeceutical potential. Recently, a great deal of interest has focused on the health-promoting effects of marine bioactive compounds. Carbohydrates are the major and abundant constituent of marine algae and have been utilized in cosmetic formulations, as moisturizing and thickening agents for example. In addition, marine carbohydrates have been suggested as promising bioactive biomaterials for their various properties beneficial to skin, including antioxidant, anti-melanogenic and skin anti-aging properties. Therefore, marine algae carbohydrates have potential skin health benefits for value-added cosmeceutical applications. The present review focuses on the various biological capacities and potential skin health benefits of bioactive marine carbohydrates. Full article

(This article belongs to the Special Issue Anti-Photoagaing and Photo-Protective Compounds from Marine Organisms)

12 pages, 1914 KiB

Open AccessArticle

Oxysterols from a Marine Sponge Inflatella sp. and Their Action in 6-Hydroxydopamine-Induced Cell Model of Parkinson’s Disease

by Sophia A. Kolesnikova, Ekaterina G. Lyakhova, Anatoly I. Kalinovsky, Roman S. Popov, Ekaterina A. Yurchenko and Valentin A. Stonik

Mar. Drugs 2018, 16(11), 458; https://doi.org/10.3390/md16110458 - 21 Nov 2018

Cited by 13 | Viewed by 4045

Abstract

Four new oxysterols 1–4 along with previously known oxygenated sterols 5–14 were isolated from the sponge Inflatella sp., collected from the Sea of Okhotsk. Structures of 1–4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses [...] Read more.

Four new oxysterols 1–4 along with previously known oxygenated sterols 5–14 were isolated from the sponge Inflatella sp., collected from the Sea of Okhotsk. Structures of 1–4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses as well as by comparison of the corresponding experimental data with those reported in literature. The influence of compounds 1–14 on the viability of neuronal Neuro2a cells treated by 6-hydroxydopamine and reactive oxygen species (ROS) formation in these cells was investigated. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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15 pages, 1793 KiB

Open AccessArticle

Neuroprotective Activity of Some Marine Fungal Metabolites in the 6-Hydroxydopamin- and Paraquat-Induced Parkinson’s Disease Models

by Ekaterina A. Yurchenko, Ekaterina S. Menchinskaya, Evgeny A. Pislyagin, Phan Thi Hoai Trinh, Elena V. Ivanets, Olga F. Smetanina and Anton N. Yurchenko

Mar. Drugs 2018, 16(11), 457; https://doi.org/10.3390/md16110457 - 21 Nov 2018

Cited by 32 | Viewed by 5417

Abstract

A new melatonin analogue 6-hydroxy-N-acetyl-β-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid [...] Read more.

A new melatonin analogue 6-hydroxy-N-acetyl-β-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid (2) and 8-methoxy-3,5-dimethylisochroman-6-ol (3) from Penicillium sp. KMM 4672, candidusin A (4) and 4″-dehydroxycandidusin A (5) from Aspergillus sp. KMM 4676, and diketopiperazine mactanamide (6) from Aspergillus flocculosus, were investigated in the 6-hydroxydopamine (6-OHDA)- and paraquat (PQ)-induced Parkinson’s disease (PD) cell models. All of them protected Neuro2a cells against the damaging influence of 6-OHDA to varying degrees. This effect may be realized via a reactive oxygen species (ROS) scavenging pathway. The new melatonin analogue more effectively protected Neuro2A cells against the 6-OHDA-induced neuronal death, in comparison with melatonin, as well as against the PQ-induced neurotoxicity. Dehydroxylation at C-3″ and C-4″ significantly increased free radical scavenging and neuroprotective activity of candidusin-related p-terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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17 pages, 4080 KiB

Open AccessArticle

Cacolides: Sesterterpene Butenolides from a Southern Australian Marine Sponge, Cacospongia sp.

by Shamsunnahar Khushi, Laizuman Nahar, Angela A. Salim and Robert J. Capon

Mar. Drugs 2018, 16(11), 456; https://doi.org/10.3390/md16110456 - 20 Nov 2018

Cited by 15 | Viewed by 4948

Abstract

Chemical analysis of a marine sponge, Cacospongia sp. (CMB-03404), obtained during deep sea commercial fishing activities off the southern coast of Australia, yielded an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides, cacolides A–L (1–12), together with biosynthetically related norsesterterpene carboxylic acids, [...] Read more.

Chemical analysis of a marine sponge, Cacospongia sp. (CMB-03404), obtained during deep sea commercial fishing activities off the southern coast of Australia, yielded an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides, cacolides A–L (1–12), together with biosynthetically related norsesterterpene carboxylic acids, cacolic acids A–C (13–15). Structures were assigned on the basis of detailed spectroscopic analysis with comparisons to known natural products and biosynthetic considerations. In addition to revealing new chemical diversity, this study provided a valuable platform for comparing and contrasting the capabilities of the traditional dereplication technologies of HPLC-DAD, HPLC-MS and NMR, with those of the emerging HPLC-MS/MS approach known as global natural products social molecular networking (GNPS), as applied to marine sponge sesterterpene tetronic acids. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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15 pages, 3396 KiB

Open AccessArticle

Chitosan Oligosaccharides Improve Glucolipid Metabolism Disorder in Liver by Suppression of Obesity-Related Inflammation and Restoration of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ)

by Yibo Bai, Junping Zheng, Xubing Yuan, Siming Jiao, Cui Feng, Yuguang Du, Hongtao Liu and Lanyan Zheng

Mar. Drugs 2018, 16(11), 455; https://doi.org/10.3390/md16110455 - 19 Nov 2018

Cited by 44 | Viewed by 5475

Abstract

Chitosan oligosaccharides (COS) display various biological activities. In this study, we aimed to explore the preventive effects of COS on glucolipid metabolism disorder using palmitic acid (PA)-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6J mice as experimental models in vitro and in vivo, [...] Read more.

Chitosan oligosaccharides (COS) display various biological activities. In this study, we aimed to explore the preventive effects of COS on glucolipid metabolism disorder using palmitic acid (PA)-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6J mice as experimental models in vitro and in vivo, respectively. The results showed that COS pretreatment for 12 h significantly ameliorated lipid accumulation in HepG2 cells exposed to PA for 24 h, accompanied by a reversing of the upregulated mRNA expression of proinflammatory cytokines (IL-6, MCP-1, TNF-α) and glucolipid metabolism-related regulators (SCD-1, ACC1, PCK1-α). In addition, COS treatment alleviated glucolipid metabolism disorder in mice fed with HFD for five months, including reduction in body weight and fasting glucose, restoration of intraperitoneal glucose tolerance, and suppression of overexpression of proinflammatory cytokines and glucolipid metabolism-related regulators. Furthermore, our study found that COS pretreatment significantly reversed the downregulation of PPARγ at transcriptional and translational levels in both PA-induced HepG2 cells and liver tissues of HFD-fed mice. In summary, the study suggests that COS can improve glucolipid metabolism disorder by suppressing inflammation and upregulating PPARγ expression. This indicates a novel application of COS in preventing and treating glucolipid metabolism-related diseases. Full article

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

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14 pages, 1701 KiB

Open AccessArticle

Investigation of Different Molecular Weight Fucoidan Fractions Derived from New Zealand Undaria pinnatifida in Combination with GroA Therapy in Prostate Cancer Cell Lines

by Xu Yang, Sheng Wang, Sari Schokoroy Trangle, Yan Li, William Lindsey White, Jinyao Li, Tianlei Ying, Qingjun Kong, Yu Zhao and Jun Lu

Mar. Drugs 2018, 16(11), 454; https://doi.org/10.3390/md16110454 - 18 Nov 2018

Cited by 17 | Viewed by 4710

Abstract

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, has been shown to possess various antioxidant, anticoagulant, antiviral, and anticancer functions. In this study, we focused on low molecular weight fucoidan (LMWF) which was extracted from New Zealand Undaria pinnatifida, and investigated its [...] Read more.

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, has been shown to possess various antioxidant, anticoagulant, antiviral, and anticancer functions. In this study, we focused on low molecular weight fucoidan (LMWF) which was extracted from New Zealand Undaria pinnatifida, and investigated its anti-proliferative effects, combined with a quadruplex-forming oligonucleotide aptamer (GroA, AS1411), a powerful cell surface Nucleolin inhibitor, in prostate cancer cells. We examined LMWF (<10 kDa) and compared it with laboratory grade Fucoidan purchased from Sigma (FS), all extracted from the same seaweed species U. pinnatifida. We found that LMWF significantly improved the anti-proliferative effect of GroA, as it decreased cancer cell growth and viability and increased cell death. This research may provide the foundation for LMWF to be used against prostate cancers as a supplement therapy in combination with other therapeutic agents. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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15 pages, 1902 KiB

Open AccessArticle

Omega-3 Monoacylglyceride Effects on Longevity, Mitochondrial Metabolism and Oxidative Stress: Insights from Drosophila melanogaster

by Camille M. Champigny, Robert P. J. Cormier, Chloé J. Simard, Patrick-Denis St-Coeur, Samuel Fortin and Nicolas Pichaud

Mar. Drugs 2018, 16(11), 453; https://doi.org/10.3390/md16110453 - 16 Nov 2018

Cited by 12 | Viewed by 4820

Abstract

During the last decade, essential polyunsaturated fatty acids (PUFAs) such as eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine sources have been investigated as nonpharmacological dietary supplements to improve different pathological conditions, as well as aging. The aim of this study [...] Read more.

During the last decade, essential polyunsaturated fatty acids (PUFAs) such as eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine sources have been investigated as nonpharmacological dietary supplements to improve different pathological conditions, as well as aging. The aim of this study was to determine the effects of dietary n-3 PUFA monoacylglycerides (MAG, both EPA and DHA) on the mitochondrial metabolism and oxidative stress of a short-lifespan model, Drosophila melanogaster, sampled at five different ages. Our results showed that diets supplemented with MAG-EPA and MAG-DHA increased median lifespan by 14.6% and decreased mitochondrial proton leak resulting in an increase of mitochondrial coupling. The flies fed on MAG-EPA also had higher electron transport system capacity and mitochondrial oxidative capacities. Moreover, both n-3 PUFAs delayed the occurrence of lipid peroxidation but only flies fed the MAG-EPA diet showed maintenance of superoxide dismutase activity during aging. Our study therefore highlights the potential of n-3 PUFA monoacylglycerides as nutraceutical compounds to delay the onset of senescence by acting directly or indirectly on the mitochondrial metabolism and suggests that Drosophila could be a relevant model for the study of the fundamental mechanisms linking the effects of n-3 PUFAs to aging. Full article

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20 pages, 3220 KiB

Open AccessArticle

New Invasive Nemertean Species (Cephalothrix Simula) in England with High Levels of Tetrodotoxin and a Microbiome Linked to Toxin Metabolism

by Andrew D. Turner, David Fenwick, Andy Powell, Monika Dhanji-Rapkova, Charlotte Ford, Robert G. Hatfield, Andres Santos, Jaime Martinez-Urtaza, Tim P. Bean, Craig Baker-Austin and Paul Stebbing

Mar. Drugs 2018, 16(11), 452; https://doi.org/10.3390/md16110452 - 16 Nov 2018

Cited by 46 | Viewed by 9612

Abstract

The marine nemertean Cephalothrix simula originates from the Pacific Ocean but in recent years has been discovered in northern Europe. The species has been associated with high levels of the marine neurotoxin Tetrodotoxin, traditionally associated with Pufferfish Poisoning. This study reports the first [...] Read more.

The marine nemertean Cephalothrix simula originates from the Pacific Ocean but in recent years has been discovered in northern Europe. The species has been associated with high levels of the marine neurotoxin Tetrodotoxin, traditionally associated with Pufferfish Poisoning. This study reports the first discovery of two organisms of C. simula in the UK, showing the geographical extent of this species is wider than originally described. Species identification was initially conducted morphologically, with confirmation by Cox 1 DNA sequencing. 16S gene sequencing enabled the taxonomic assignment of the microbiome, showing the prevalence of a large number of bacterial genera previously associated with TTX production including Alteromonas, Vibrio and Pseudomonas. LC-MS/MS analysis of the nemertean tissue revealed the presence of multiple analogues of TTX, dominated by the parent TTX, with a total toxin concentration quantified at 54 µg TTX per g of tissue. Pseudomonas luteola isolated from C. simula, together with Vibrio alginolyticus from the native nemertean Tubulanus annulatus, were cultured at low temperature and both found to contain TTX. Overall, this paper confirms the high toxicity of a newly discovered invasive nemertean species with links to toxin-producing marine bacteria and the potential risk to human safety. Further work is required to assess the geographical extent and toxicity range of C. simula along the UK coast in order to properly gauge the potential impacts on the environment and human safety. Full article

(This article belongs to the Special Issue Marine Bacterial Toxins)

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11 pages, 667 KiB

Open AccessArticle

Diphenyl Ethers from a Marine-Derived Aspergillus sydowii

by Ya-Nan Wang, Yan-Hua Mou, Yu Dong, Yan Wu, Bing-Yu Liu, Jian Bai, Dao-Jiang Yan, Le Zhang, Dan-Qing Feng, Yue-Hu Pei and You-Cai Hu

Mar. Drugs 2018, 16(11), 451; https://doi.org/10.3390/md16110451 - 16 Nov 2018

Cited by 28 | Viewed by 4397

Abstract

Six new diphenyl ethers (1–6) along with eleven known analogs were isolated from the ethyl acetate extract of a marine-derived Aspergillus sydowii guided by LC-UV-MS. Their structures were unambiguously characterized by HRESIMS, NMR, as well as chemical derivatization. Compounds [...] Read more.

Six new diphenyl ethers (1–6) along with eleven known analogs were isolated from the ethyl acetate extract of a marine-derived Aspergillus sydowii guided by LC-UV-MS. Their structures were unambiguously characterized by HRESIMS, NMR, as well as chemical derivatization. Compounds 1 and 2 are rare diphenyl ether glycosides containing d-ribose. The absolute configuration of the sugar moieties in compounds 1–3 was determined by a LC-MS method. All the compounds were evaluated for their cytotoxicities against eight cancer cell lines, including 4T1, U937, PC3, HL-60, HT-29, A549, NCI-H460, and K562, and compounds 1, 5, 6, and 8–11 were found to exhibit selective cytotoxicity against different cancer cell lines. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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20 pages, 4434 KiB

Open AccessArticle

Pharmaceutical Standardization and Physicochemical Characterization of Traditional Ayurvedic Marine Drug: Incinerated Conch Shell (Shankha Bhasma)

by Sandeep Chavan, Sonali Tayade, Vidya Gupta, Vineeta Deshmukh and Sadanand Sardeshmukh

Mar. Drugs 2018, 16(11), 450; https://doi.org/10.3390/md16110450 - 15 Nov 2018

Cited by 15 | Viewed by 9984

Abstract

Natural resources such as plants, animals and minerals have always been used by mankind to develop drugs and marine world is no exception. Marine by-products like conches, pearls, mother of pearl shells, corals and so forth have been used by traditional Ayurvedic practitioners [...] Read more.

Natural resources such as plants, animals and minerals have always been used by mankind to develop drugs and marine world is no exception. Marine by-products like conches, pearls, mother of pearl shells, corals and so forth have been used by traditional Ayurvedic practitioners for centuries. The unique methods of these preparations are scientifically designed to eliminate unwanted impurities and convert them into bioavailable form. In this study, Conch (Xanchus pyrum) was used as a marine resource of calcium carbonate and was converted pharmaceutically from its aragonite form to calcite. All the steps of preparations and changes in the properties therein were documented and validated. Further, traditional as well as modern analytical tools were used to study its physical and chemical characters to develop a monograph. The physical characterization included particle size, X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA) and Fourier Transform Infra-red (FTIR). Metal composition and heavy metal limits were determined using Inductively Coupled Plasma Optical Emission Spectrometry (ICPOES). This study revealed the rearrangement of aragonite crystals into calcite form by grinding, trituration with aloe vera juice and incineration under controlled conditions. Moreover, the finished product was found to be devoid of organic matrix that is nacre. This study creates a foundation for the development of a master formula for commonly used Shankha Bhasma in Ayurvedic medicines. Full article

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9 pages, 615 KiB

Open AccessArticle

Potential Antiviral Xanthones from a Coastal Saline Soil Fungus Aspergillus iizukae

by Hui-Hui Kang, Huai-Bin Zhang, Mei-Jia Zhong, Li-Ying Ma, De-Sheng Liu, Wei-Zhong Liu and Hong Ren

Mar. Drugs 2018, 16(11), 449; https://doi.org/10.3390/md16110449 - 15 Nov 2018

Cited by 31 | Viewed by 4481

Abstract

Five new (1–5) and two known xanthones (6 and 7), one of the latter (6) obtained for the first time as a natural product, together with three known anthraquinones, questin, penipurdin A, and questinol, were [...] Read more.

Five new (1–5) and two known xanthones (6 and 7), one of the latter (6) obtained for the first time as a natural product, together with three known anthraquinones, questin, penipurdin A, and questinol, were isolated from the coastal saline soil-derived Aspergillus iizukae by application of an OSMAC (one strain many compounds) approach. Their structures were determined by interpretation of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, as well as comparison of these data with those of related known compounds. Antiviral activity of xanthones 1−7 was evaluated through the cytopathic effect (CPE) inhibition assay, and compound 2 exhibited distinctly strong activity towards influenza virus (H1N1), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) with IC₅₀ values of 44.6, 21.4, and 76.7 μM, respectively, which indicated that it was worth to further investigate it as a potential lead compound. The preliminary structure-activity relationship of the xanthones is discussed. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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13 pages, 3168 KiB

Open AccessArticle

Unstable Tetramic Acid Derivatives from the Deep-Sea-Derived Fungus Cladosporium sphaerospermum EIODSF 008

by Xiao Liang, Zhong-Hui Huang, Xuan Ma and Shu-Hua Qi

Mar. Drugs 2018, 16(11), 448; https://doi.org/10.3390/md16110448 - 15 Nov 2018

Cited by 20 | Viewed by 3813

Abstract

Seven new unstable tetramic acid derivatives, cladosporiumins I-O (1–7), together with the known analogue cladodionen (8) were isolated from the extract of the deep-sea-derived fungus Cladosporium sphaerospermum EIODSF 008. Their structures were elucidated by spectroscopic analysis, quantum [...] Read more.

Seven new unstable tetramic acid derivatives, cladosporiumins I-O (1–7), together with the known analogue cladodionen (8) were isolated from the extract of the deep-sea-derived fungus Cladosporium sphaerospermum EIODSF 008. Their structures were elucidated by spectroscopic analysis, quantum chemical calculations and ECD spectra. Compound 4 was a Mg complex of tetramic acid derivative. In acidic solvent, 4 could change to 1 and 6, and 7 could change to 5. In addition, 1, 5 and 8 existed as two exchangeable isomers, respectively. The structures of cladosporiumins E-H were reassigned as their Na complexes. The antibacterial and cytotoxic activities of 1–8 were also evaluated. However, because of their instability, all of the isolated compounds did not show significant antibacterial activity as the preliminary EtOAc extracts of the fungal strain. Full article

(This article belongs to the Special Issue Deep-Sea Natural Products II)

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18 pages, 8682 KiB

Open AccessArticle

Chitosan Oleate Salt as an Amphiphilic Polymer for the Surface Modification of Poly-Lactic-Glycolic Acid (PLGA) Nanoparticles. Preliminary Studies of Mucoadhesion and Cell Interaction Properties

by Dalila Miele, Silvia Rossi, Giuseppina Sandri, Barbara Vigani, Milena Sorrenti, Paolo Giunchedi, Franca Ferrari and Maria Cristina Bonferoni

Mar. Drugs 2018, 16(11), 447; https://doi.org/10.3390/md16110447 - 15 Nov 2018

Cited by 11 | Viewed by 4007

Abstract

Most of the methods of poly-lactic-glycolic acid (PLGA) preparation involve the passage through the emulsification of a PLGA organic solution in water followed by solvent evaporation or extraction. The choice of the droplet stabilizer during the emulsion step is critical for the dimensions [...] Read more.

Most of the methods of poly-lactic-glycolic acid (PLGA) preparation involve the passage through the emulsification of a PLGA organic solution in water followed by solvent evaporation or extraction. The choice of the droplet stabilizer during the emulsion step is critical for the dimensions and the surface characteristics of the nanoparticles (NPs). In the present work, a recently described ionic amphiphilic chitosan derivative, chitosan oleate salt (CS-OA), was proposed for the first time to prepare PLGA NPs. A full factorial design was used to understand the effect of some formulation and preparation parameters on the NP dimensions and on encapsulation efficiency (EE%) of Nile red, used as a tracer. On the basis of the DoE study, curcumin loaded NPs were prepared, having 329 ± 42 nm dimensions and 68.75% EE%. The presence of a chitosan coating at the surface was confirmed by positive zeta potential and resulted in mucoadhesion behavior. The expected improvement of the interaction of the chitosan surface modified nanoparticles with cell membrane surface was confirmed in Caco-2 cell culture by the internalization of the loaded curcumin. Full article

(This article belongs to the Special Issue Marine Chitin 2019)

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15 pages, 3942 KiB

Open AccessArticle

Identification of Novel Gymnodimines and Spirolides from the Marine Dinoflagellate Alexandrium ostenfeldii

by Christian Zurhelle, Joyce Nieva, Urban Tillmann, Tilmann Harder, Bernd Krock and Jan Tebben

Mar. Drugs 2018, 16(11), 446; https://doi.org/10.3390/md16110446 - 14 Nov 2018

Cited by 43 | Viewed by 5452

Abstract

Cyclic imine toxins are neurotoxic, macrocyclic compounds produced by marine dinoflagellates. Mass spectrometric screenings of extracts from natural plankton assemblages revealed a high chemical diversity among this toxin class, yet only few toxins are structurally known. Here we report the structural characterization of [...] Read more.

Cyclic imine toxins are neurotoxic, macrocyclic compounds produced by marine dinoflagellates. Mass spectrometric screenings of extracts from natural plankton assemblages revealed a high chemical diversity among this toxin class, yet only few toxins are structurally known. Here we report the structural characterization of four novel cyclic-imine toxins (two gymnodimines (GYMs) and two spirolides (SPXs)) from cultures of Alexandrium ostenfeldii. A GYM with m/z 510 (1) was identified as 16-desmethylGYM D. A GYM with m/z 526 was identified as the hydroxylated degradation product of (1) with an exocyclic methylene at C-17 and an allylic hydroxyl group at C-18. This compound was named GYM E (2). We further identified a SPX with m/z 694 as 20-hydroxy-13,19-didesmethylSPX C (10) and a SPX with m/z 696 as 20-hydroxy-13,19-didesmethylSPX D (11). This is the first report of GYMs without a methyl group at ring D and SPXs with hydroxyl groups at position C-20. These compounds can be conceived as derivatives of the same nascent polyketide chain, supporting the hypothesis that GYMs and SPXs are produced through common biosynthetic genes. Both novel GYMs 1 and 2 were detected in significant amounts in extracts from natural plankton assemblages (1: 447 pg; 2: 1250 pg; 11: 40 pg per mL filtered seawater respectively). Full article

(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)

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18 pages, 3761 KiB

Open AccessArticle

Anticoagulant Properties of a Green Algal Rhamnan-type Sulfated Polysaccharide and Its Low-molecular-weight Fragments Prepared by Mild Acid Degradation

by Xue Liu, Peng Du, Xiao Liu, Sujian Cao, Ling Qin, Meijia He, Xiaoxi He and Wenjun Mao

Mar. Drugs 2018, 16(11), 445; https://doi.org/10.3390/md16110445 - 12 Nov 2018

Cited by 35 | Viewed by 4608

Abstract

The active sulfated polysaccharide from seaweed possesses important pharmaceutical and biomedical potential. In the study, Monostroma sulfated polysaccharide (MSP) was obtained from Monostroma angicava, and the low-molecular-weight fragments of MSP (MSP-Fs: MSP-F1–MSP-F6) were prepared by controlled acid degradation. The molecular weights of [...] Read more.

The active sulfated polysaccharide from seaweed possesses important pharmaceutical and biomedical potential. In the study, Monostroma sulfated polysaccharide (MSP) was obtained from Monostroma angicava, and the low-molecular-weight fragments of MSP (MSP-Fs: MSP-F1–MSP-F6) were prepared by controlled acid degradation. The molecular weights of MSP and MSP-F1–MSP-F6 were 335 kDa, 240 kDa, 90 kDa, 40 kDa, 24 kDa, 12 kDa, and 6.8 kDa, respectively. The polysaccharides were sulfated rhamnans that consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ units with partial sulfation at C-2 of →3)-α-l-Rhap-(1→ and C-3 of →2)-α-l-Rhap-(1→. Anticoagulant properties in vitro of MSP and MSP-F1–MSP-F6 were evaluated by studying the activated partial thromboplastin time, thrombin time, and prothrombin time. Anticoagulant activities in vivo of MSP and MSP-F4 were further evaluated; their fibrin(ogen)olytic activities in vivo and thrombolytic properties in vitro were also assessed by D-dimer, fibrin degradation products, plasminogen activator inhibitior-1, and clot lytic rate assays. The results showed that MSP and MSP-F1–MSP-F4 with molecular weights of 24–240 kDa had strong anticoagulant activities. A decrease in the molecular weight of MSP-Fs was accompanied by a decrease in the anticoagulant activity, and higher anticoagulant activity requires a molecular weight of over 12 kDa. MSP and MSP-F4 possessed strong anticoagulant activities in vivo, as well as high fibrin(ogen)olytic and thrombolytic activities. MSP and MSP-F4 have potential as drug or helpful food supplements for human health. Full article

(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)

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15 pages, 2938 KiB

Open AccessArticle

Novel Bioactive Peptides from Meretrix meretrix Protect Caenorhabditis elegans against Free Radical-Induced Oxidative Stress through the Stress Response Factor DAF-16/FOXO

by Weizhang Jia, Qiong Peng, Linnan Su, Xuesong Yu, Chung Wah Ma, Ming Liang, Xiquan Yin, Yongdong Zou and Zebo Huang

Mar. Drugs 2018, 16(11), 444; https://doi.org/10.3390/md16110444 - 11 Nov 2018

Cited by 36 | Viewed by 4919

Abstract

The hard clam Meretrix meretrix, which has been traditionally used as medicine and seafood, was used in this study to isolate antioxidant peptides. First, a peptide-rich extract was tested for its protective effect against paraquat-induced oxidative stress using the nematode model Caenorhabditis [...] Read more.

The hard clam Meretrix meretrix, which has been traditionally used as medicine and seafood, was used in this study to isolate antioxidant peptides. First, a peptide-rich extract was tested for its protective effect against paraquat-induced oxidative stress using the nematode model Caenorhabditis elegans. Then, three novel antioxidant peptides; MmP4 (LSDRLEETGGASS), MmP11 (KEGCREPETEKGHR) and MmP19 (IVTNWDDMEK), were identified and were found to increase the resistance of nematodes against paraquat. Circular dichroism spectroscopy revealed that MmP4 was predominantly in beta-sheet conformation, while MmP11 and MmP19 were primarily in random coil conformation. Using transgenic nematode models, the peptides were shown to promote nuclear translocation of the DAF-16/FOXO transcription factor, a pivotal regulator of stress response and lifespan, and induce the expression of superoxide dismutase 3 (SOD-3), an antioxidant enzyme. Analysis of DAF-16 target genes by real-time PCR reveals that sod-3 was up-regulated by MmP4, MmP11 and MmP19 while ctl-1 and ctl-2 were also up-regulated by MmP4. Further examination of daf-16 using RNA interference suggests that the peptide-increased resistance of C. elegans to oxidative stress was DAF-16 dependent. Taken together, these data demonstrate the antioxidant activity of M. meretrix peptides, which are associated with activation of the stress response factor DAF-16 and regulation of the antioxidant enzyme genes. Full article

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12 pages, 1745 KiB

Open AccessArticle

Anti-Acanthamoeba Activity of Brominated Sesquiterpenes from Laurencia johnstonii

by Sara García-Davis, Ines Sifaoui, María Reyes-Batlle, Ezequiel Viveros-Valdez, José E. Piñero, Jacob Lorenzo-Morales, José J. Fernández and Ana R. Díaz-Marrero

Mar. Drugs 2018, 16(11), 443; https://doi.org/10.3390/md16110443 - 11 Nov 2018

Cited by 27 | Viewed by 5077

Abstract

Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify [...] Read more.

Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers α-bromocuparane (4) and α-isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)–(9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3α-bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane. Full article

(This article belongs to the Special Issue Bioassay-Guided Isolation of Marine Natural Products for Drug Discovery)

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15 pages, 4650 KiB

Open AccessArticle

Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins

by Yu-Dong Zhou, Jun Li, Lin Du, Fakhri Mahdi, Thuy P. Le, Wei-Lun Chen, Steven M. Swanson, Kounosuke Watabe and Dale G. Nagle

Mar. Drugs 2018, 16(11), 442; https://doi.org/10.3390/md16110442 - 10 Nov 2018

Cited by 17 | Viewed by 4420

Abstract

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated [...] Read more.

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery. Full article

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

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11 pages, 1575 KiB

Open AccessArticle

Protective Effect of Pyrogallol-Phloroglucinol-6,6-Bieckol from Ecklonia cava on Monocyte-Associated Vascular Dysfunction

by Seyeon Oh, Myeongjoo Son, Hye Sun Lee, Hyun-Soo Kim, You-Jin Jeon and Kyunghee Byun

Mar. Drugs 2018, 16(11), 441; https://doi.org/10.3390/md16110441 - 9 Nov 2018

Cited by 35 | Viewed by 4784

Abstract

Ecklonia cava (E. cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in [...] Read more.

Ecklonia cava (E. cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory Agents)

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10 pages, 1755 KiB

Open AccessFeature PaperArticle

20-Nor-Isopimarane Epimers Produced by Aspergillus wentii SD-310, a Fungal Strain Obtained from Deep Sea Sediment

by Xiao-Dong Li, Xin Li, Xiao-Ming Li, Gang-Ming Xu, Yang Liu and Bin-Gui Wang

Mar. Drugs 2018, 16(11), 440; https://doi.org/10.3390/md16110440 - 9 Nov 2018

Cited by 24 | Viewed by 3902

Abstract

Four new uncommon 20-nor-isopimarane diterpenoid epimers, aspewentins I−L (1–4), together with a new methylated derivative of 3, aspewentin M (5), were isolated from the deep sea sediment-derived fungus Aspergillus wentii SD-310. The very similar structures of [...] Read more.

Four new uncommon 20-nor-isopimarane diterpenoid epimers, aspewentins I−L (1–4), together with a new methylated derivative of 3, aspewentin M (5), were isolated from the deep sea sediment-derived fungus Aspergillus wentii SD-310. The very similar structures of these epimers made the separation and purification procedures difficult. The structures of compounds 1–5 were illustrated based on spectroscopic analysis, and the absolute configurations of compounds 1–5 were unambiguously determined by the combination of NOESY, time-dependent density functional (TDDFT)-ECD calculations, and X-ray crystallographic analysis. These metabolites represented the rare examples of 20-nor-isopimarane analogues possessing a cyclohexa-2,5-dien-1-one moiety. These compounds were tested for antimicrobial activities against human and aquatic pathogenic bacteria, as well as plant-pathogenic fungi. While compounds 1 and 2 exhibited inhibitory activities against zoonotic pathogenic bacteria such as Escherichia coli, Edwardsiella tarda, Vibrio harveyi, and V. parahaemolyticus, compound 5 showed potent activity against the plant pathogen Fusarium graminearum. Full article

(This article belongs to the Special Issue Marine Antimicrobial Agents)

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18 pages, 8464 KiB

Open AccessArticle

Folate Receptor-Targeted and GSH-Responsive Carboxymethyl Chitosan Nanoparticles Containing Covalently Entrapped 6-Mercaptopurine for Enhanced Intracellular Drug Delivery in Leukemia

by Xuan Wei, Jianhong Liao, Zahra Davoudi, Hua Zheng, Jingru Chen, Dan Li, Xiong Xiong, Yihua Yin, Xiuxiang Yu, Jinghui Xiong and Qun Wang

Mar. Drugs 2018, 16(11), 439; https://doi.org/10.3390/md16110439 - 8 Nov 2018

Cited by 99 | Viewed by 7015

Abstract

For enhanced intracellular accumulation of 6-mercaptopurine (6-MP) in leukemia, a folate receptor-targeted and glutathione (GSH)-responsive polymeric prodrug nanoparticle was made. The nanoparticles were prepared by conjugating 6-MP to carboxymethyl chitosan via a GSH-sensitive carbonyl vinyl sulfide linkage, ultrasonic self-assembly and surface decoration with [...] Read more.

For enhanced intracellular accumulation of 6-mercaptopurine (6-MP) in leukemia, a folate receptor-targeted and glutathione (GSH)-responsive polymeric prodrug nanoparticle was made. The nanoparticles were prepared by conjugating 6-MP to carboxymethyl chitosan via a GSH-sensitive carbonyl vinyl sulfide linkage, ultrasonic self-assembly and surface decoration with folate. The TEM graphs shows that the as-synthesized nanoparticles are spherical with a particle size of 170~220 nm. In vitro drug release of nanoparticles demonstrated acceptable stability in PBS containing 20 μM GSH at pH 7.4. However, the cumulative drug release rate of the samples containing 20 mM and 10 mM GSH medium reached 78.9% and 64.8%, respectively, in pH 5.0 at 20 h. This indicated that this nano-sized system is highly sensitive to GSH. The inhibition ratio of folate-modified nanoparticles compared to unmodified nanoparticles was higher in cancer cells (human promyelocytic leukemia cells, HL-60) while their cytotoxicity was lower in normal cells (mouse fibroblast cell lines, L929). Furthermore, in vitro cancer cell incubation studies confirmed that folate-modified nanoparticles therapeutics were significantly more effective than unmodified nanoparticles therapeutics. Our results suggest that folate receptor-targeting and GSH-stimulation can significantly elevate tumour intracellular drug release. Therefore, folate-modified nanoparticles containing chemoradiotherapy is a potential treatment for leukemia therapy. Full article

(This article belongs to the Special Issue Marine Biopolymers and Drug Delivery)

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8 pages, 788 KiB

Open AccessArticle

Anti-MRSA Sesquiterpenes from the Semi-Mangrove Plant Myoporum bontioides A. Gray

by Li-Mei Dong, Li-Lan Huang, Hang Dai, Qiao-Lin Xu, Jin-Kui Ouyang, Xu-Chao Jia, Wen-Xiang Gu and Jian-Wen Tan

Mar. Drugs 2018, 16(11), 438; https://doi.org/10.3390/md16110438 - 8 Nov 2018

Cited by 22 | Viewed by 3867

Abstract

The striking rise of methicillin-resistant Staphylococcus aureus (MRSA) infections has become a serious threat to public health worldwide. In an effort to search for new anti-MRSA agents from natural products, a bioassay-guided phytochemical study was conducted on the semi-mangrove plant Myoporum bontioides A. [...] Read more.

The striking rise of methicillin-resistant Staphylococcus aureus (MRSA) infections has become a serious threat to public health worldwide. In an effort to search for new anti-MRSA agents from natural products, a bioassay-guided phytochemical study was conducted on the semi-mangrove plant Myoporum bontioides A. Gray, which led to the isolation of two new sesquiterpene alkaloids (1 and 2) and six known furanosesquiterpenes (3–8). Their structures were elucidated on the basis of extensive analysis of their 1D, 2D NMR and mass spectroscopic data. These two new alkaloids (1 and 2) displayed potent anti-MRSA activity with MIC value of 6.25 μg/mL. This is the first report of sesquiterpene alkaloids from the plants of Myoporum genus and their anti-MRSA activity. Full article

(This article belongs to the Special Issue Bioassay-Guided Isolation of Marine Natural Products for Drug Discovery)

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17 pages, 2127 KiB

Open AccessArticle

6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity

by Xiaxia Di, Caroline Rouger, Ingibjorg Hardardottir, Jona Freysdottir, Tadeusz F. Molinski, Deniz Tasdemir and Sesselja Omarsdottir

Mar. Drugs 2018, 16(11), 437; https://doi.org/10.3390/md16110437 - 8 Nov 2018

Cited by 31 | Viewed by 6292

Abstract

An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A–C (1–3) and four known compounds, barettin (4), 8,9-dihydrobarettin ( [...] Read more.

An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A–C (1–3) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and l-6-bromohypaphorine (7). The chemical structures of compounds 1–7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A (1) was assigned by ECD analysis and Marfey’s method employing the new reagent l-N^α-(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4⁺ T cells decreased T cell secretion of IFN-γ, indicating a reduction in Th1 differentiation. Although barettin (4) reduced DC secretion of IL-12p40 and IL-10 (IC₅₀ values 11.8 and 21.0 μM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-γ or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory Agents)

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11 pages, 713 KiB

Open AccessArticle

Ishophloroglucin A, a Novel Phlorotannin for Standardizing the Anti-α-Glucosidase Activity of Ishige okamurae

by BoMi Ryu, Yunfei Jiang, Hyun-Soo Kim, Jee-Min Hyun, Sang-Bin Lim, Yong Li and You-Jin Jeon

Mar. Drugs 2018, 16(11), 436; https://doi.org/10.3390/md16110436 - 8 Nov 2018

Cited by 32 | Viewed by 4560

Abstract

Nutraceutical use of algae requires understanding of the diversity and significance of their active compositions for intended activities. Ishige okamurae (I. okamurae) extract is well-known to possess α-glucosidase inhibitory activity; however, studies are needed to investigate its active composition in order [...] Read more.

Nutraceutical use of algae requires understanding of the diversity and significance of their active compositions for intended activities. Ishige okamurae (I. okamurae) extract is well-known to possess α-glucosidase inhibitory activity; however, studies are needed to investigate its active composition in order to standardize its α-glucosidase inhibitory activity. In this study, we observed the intensity of the dominant compounds of each I. okamurae extract harvested between 2016 and 2017, and the different potency of each I. okamurae extract against α-glucosidase. By comparing the anti-α-glucosidase ability of the dominant compounds, a novel Ishophloroglucin A with highest α-glucosidase inhibitory activity was identified and suggested for standardization of anti-α-glucosidase activity in I. okamurae extract. Additionally, a validated analytical method for measurement of Ishophloroglucin A for future standardization of I. okamurae extract was established in this study. We suggest using Ishophloroglucin A to standardize anti-α-glucosidase potency of I. okamurae and propose the significance of standardization based on their composition for effective use of algae as marine-derived nutraceuticals. Full article

(This article belongs to the Special Issue Marine Small-Molecule Bioactive Agents and Therapeutic Targets)

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10 pages, 2236 KiB

Open AccessCommunication

Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp. chlorinus NRRL B-24108

by Marta Rodríguez Estévez, Maksym Myronovskyi, Nils Gummerlich, Suvd Nadmid and Andriy Luzhetskyy

Mar. Drugs 2018, 16(11), 435; https://doi.org/10.3390/md16110435 - 4 Nov 2018

Cited by 23 | Viewed by 5818

Abstract

Streptomycetes represent an important reservoir of active secondary metabolites with potential applications in the pharmaceutical industry. The gene clusters responsible for their production are often cryptic under laboratory growth conditions. Characterization of these clusters is therefore essential for the discovery of new microbial [...] Read more.

Streptomycetes represent an important reservoir of active secondary metabolites with potential applications in the pharmaceutical industry. The gene clusters responsible for their production are often cryptic under laboratory growth conditions. Characterization of these clusters is therefore essential for the discovery of new microbial pharmaceutical drugs. Here, we report the identification of the previously uncharacterized nybomycin gene cluster from the marine actinomycete Streptomyces albus subsp. chlorinus through its heterologous expression. Nybomycin has previously been reported to act against quinolone-resistant Staphylococcus aureus strains harboring a mutated gyrA gene but not against those with intact gyrA. The nybomycin-resistant mutants generated from quinolone-resistant mutants have been reported to be caused by a back-mutation in the gyrA gene that restores susceptibility to quinolones. On the basis of gene function assignment from bioinformatics analysis, we suggest a model for nybomycin biosynthesis. Full article

(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)

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16 pages, 2893 KiB

Open AccessArticle

Limonoids Containing a C₁–O–C₂₉ Moiety: Isolation, Structural Modification, and Antiviral Activity

by Jing-Ling Ren, Xiao-Peng Zou, Wan-Shan Li, Li Shen and Jun Wu

Mar. Drugs 2018, 16(11), 434; https://doi.org/10.3390/md16110434 - 4 Nov 2018

Cited by 19 | Viewed by 3606

Abstract

Five new limonoids named thaigranatins A–E (1–5), containing a C₁–O–C₂₉ moiety, were isolated from seeds of the Thai Xylocarpus granatum, collected at the mangrove swamp of Trang Province, together with the known limonoid, [...] Read more.

Five new limonoids named thaigranatins A–E (1–5), containing a C₁–O–C₂₉ moiety, were isolated from seeds of the Thai Xylocarpus granatum, collected at the mangrove swamp of Trang Province, together with the known limonoid, granatumin L (6). The structures of these compounds were established by HR-ESIMS and extensive NMR spectroscopic data. The absolute configuration of 1 was unequivocally determined by single-crystal X-ray diffraction analysis, conducted with Cu Kα radiation; whereas that of 2 or 6 was established to be the same as that of 1 by the similarity of their electronic circular dichroism (ECD) spectra. In view of the marked antiviral activity of 6, its structure was modified via hydrolysis with alkaline KOH, esterification with diazomethane and various organic acids, and oximization with hydroxyamine. Finally, 18 derivatives, viz. 7–10, 8a–8i, 9a–9b, and 10a–10c, were obtained. In vitro antiviral activities of these derivatives against human immunodeficiency virus 1 (HIV-1) and influenza A virus (IAV) were evaluated. Most notably, 8i exhibited marked inhibitory activity against HIV-1 with an IC₅₀ value of 15.98 ± 6.87 μM and a CC₅₀ value greater than 100.0 μM; whereas 10b showed significant inhibitory activity against IAV with an IC₅₀ value of 14.02 ± 3.54 μM and a CC₅₀ value greater than 100.0 μM. Full article

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17 pages, 8653 KiB

Open AccessArticle

The Antibacterial and Anti-Eukaryotic Type VI Secretion System MIX-Effector Repertoire in Vibrionaceae

by Yasmin Dar, Dor Salomon and Eran Bosis

Mar. Drugs 2018, 16(11), 433; https://doi.org/10.3390/md16110433 - 4 Nov 2018

Cited by 24 | Viewed by 6953

Abstract

Vibrionaceae is a widespread family of aquatic bacteria that includes emerging pathogens and symbionts. Many Vibrionaceae harbor a type VI secretion system (T6SS), which is a secretion apparatus used to deliver toxins, termed effectors, into neighboring cells. T6SSs mediate both antibacterial and anti-eukaryotic [...] Read more.

Vibrionaceae is a widespread family of aquatic bacteria that includes emerging pathogens and symbionts. Many Vibrionaceae harbor a type VI secretion system (T6SS), which is a secretion apparatus used to deliver toxins, termed effectors, into neighboring cells. T6SSs mediate both antibacterial and anti-eukaryotic activities. Notably, antibacterial effectors are encoded together with a gene that encodes a cognate immunity protein so as to antagonize the toxicity of the effector. The MIX (Marker for type sIX effectors) domain has been previously defined as a marker of T6SS effectors carrying polymorphic C-terminal toxins. Here, we set out to identify the Vibrionaceae MIX-effector repertoire and to analyze the various toxin domains they carry. We used a computational approach to search for the MIX-effectors in the Vibrionaceae genomes, and grouped them into clusters based on the C-terminal toxin domains. We classified MIX-effectors as either antibacterial or anti-eukaryotic, based on the presence or absence of adjacent putative immunity genes, respectively. Antibacterial MIX-effectors carrying pore-forming, phospholipase, nuclease, peptidoglycan hydrolase, and protease activities were found. Furthermore, we uncovered novel virulence MIX-effectors. These are encoded by “professional MIXologist” strains that employ a cocktail of antibacterial and anti-eukaryotic MIX-effectors. Our findings suggest that certain Vibrionaceae adapted their antibacterial T6SS to mediate interactions with eukaryotic hosts or predators. Full article

(This article belongs to the Special Issue Marine Bacterial Toxins)

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16 pages, 2710 KiB

Open AccessArticle

Extraction of Astaxanthin and Lutein from Microalga Haematococcus pluvialis in the Red Phase Using CO₂ Supercritical Fluid Extraction Technology with Ethanol as Co-Solvent

by Antonio Molino, Sanjeet Mehariya, Angela Iovine, Vincenzo Larocca, Giuseppe Di Sanzo, Maria Martino, Patrizia Casella, Simeone Chianese and Dino Musmarra

Mar. Drugs 2018, 16(11), 432; https://doi.org/10.3390/md16110432 - 3 Nov 2018

Cited by 105 | Viewed by 7645

Abstract

Astaxanthin and lutein, antioxidants used in nutraceutics and cosmetics, can be extracted from several microalgal species. In this work, investigations on astaxanthin and lutein extraction from Haematococcus pluvialis (H. pluvialis) in the red phase were carried out by means of the [...] Read more.

Astaxanthin and lutein, antioxidants used in nutraceutics and cosmetics, can be extracted from several microalgal species. In this work, investigations on astaxanthin and lutein extraction from Haematococcus pluvialis (H. pluvialis) in the red phase were carried out by means of the supercritical fluid extraction (SFE) technique, in which CO₂ supercritical fluid was used as the extracting solvent with ethanol as the co-solvent. The experimental activity was performed using a bench-scale reactor in semi-batch configuration with varying extraction times (20, 40, 60, and 80 min), temperatures (50, 65, and 80 °C) and pressures (100, 400, and 550 bar). Moreover, the performance of CO₂ SFE with ethanol was compared to that without ethanol. The results show that the highest astaxanthin and lutein recoveries were found at 65 °C and 550 bar, with ~18.5 mg/g dry weight (~92%) astaxanthin and ~7.15 mg/g dry weight (~93%) lutein. The highest astaxanthin purity and the highest lutein purity were found at 80 °C and 400 bar, and at 65 °C and 550 bar, respectively. Full article

(This article belongs to the Special Issue Marine Health Compounds: From Extraction to Food and Pharmaceutical Application)

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16 pages, 7375 KiB

Open AccessArticle

Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest

by Rosa Maria Vitale, Enrico D'Aniello, Stefania Gorbi, Andrea Martella, Cristoforo Silvestri, Maria Elisa Giuliani, Tariq Fellous, Alessandra Gentile, Marianna Carbone, Adele Cutignano, Laura Grauso, Laura Magliozzi, Gianluca Polese, Biagio D'Aniello, Fanny Defranoux, Serena Felline, Antonio Terlizzi, Antonio Calignano, Francesco Regoli, Vincenzo Di Marzo, Pietro Amodeo and Ernesto Mollo Show full author list Hide full author list

Mar. Drugs 2018, 16(11), 431; https://doi.org/10.3390/md16110431 - 3 Nov 2018

Cited by 27 | Viewed by 7176

Abstract

Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)—a bioactive component [...] Read more.

Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)—a bioactive component of the green alga Caulerpa cylindracea that has invaded the entire Mediterranean basin—is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays. On the basis of these results, we candidate CAU as a causal factor of the metabolic and behavioural disorders observed in Diplodus sargus, a native edible fish of high ecological and commercial relevance, feeding on C. cylindracea. Moreover, given the considerable interest in PPAR activators for the treatment of relevant human diseases, our findings are also discussed in terms of a possible nutraceutical/pharmacological valorisation of the invasive algal biomasses, supporting an innovative strategy for conserving biodiversity as an alternative to unrealistic campaigns for the eradication of invasive pests. Full article

(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))

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13 pages, 2717 KiB

Open AccessArticle

Influence of Preparation Methods of Chitooligosaccharides on Their Physicochemical Properties and Their Anti-Inflammatory Effects in Mice and in RAW264.7 Macrophages

by Ángela Sánchez, María Mengibar, Margarita Fernández, Susana Alemany, Angeles Heras and Niuris Acosta

Mar. Drugs 2018, 16(11), 430; https://doi.org/10.3390/md16110430 - 2 Nov 2018

Cited by 26 | Viewed by 4091

Abstract

The methods to obtain chitooligosaccharides are tightly related to the physicochemical properties of the end products. Knowledge of these physicochemical characteristics is crucial to describing the biological functions of chitooligosaccharides. Chitooligosaccharides were prepared either in a single-step enzymatic hydrolysis using chitosanase, or in [...] Read more.

The methods to obtain chitooligosaccharides are tightly related to the physicochemical properties of the end products. Knowledge of these physicochemical characteristics is crucial to describing the biological functions of chitooligosaccharides. Chitooligosaccharides were prepared either in a single-step enzymatic hydrolysis using chitosanase, or in a two-step chemical-enzymatic hydrolysis. The hydrolyzed products obtained in the single-step preparation were composed mainly of 42% fully deacetylated oligomers plus 54% monoacetylated oligomers, and they attenuated the inflammation in lipopolysaccharide-induced mice and in RAW264.7 macrophages. However, chitooligosaccharides from the two-step preparation were composed of 50% fully deacetylated oligomers plus 27% monoacetylated oligomers and, conversely, they promoted the inflammatory response in both in vivo and in vitro models. Similar proportions of monoacetylated and deacetylated oligomers is necessary for the mixtures of chitooligosaccharides to achieve anti-inflammatory effects, and it directly depends on the preparation method to which chitosan was submitted. Full article

(This article belongs to the Special Issue Marine Chitin 2019)

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