Marine Drugs

9 pages, 837 KiB

Open AccessArticle

Bioactive Secondary Metabolites from the Culture of the Mangrove-Derived Fungus Daldinia eschscholtzii HJ004

by Hai-Xia Liao, Tai-Ming Shao, Rong-Qing Mei, Guo-Lei Huang, Xue-Ming Zhou, Cai-Juan Zheng and Chang-Yun Wang

Mar. Drugs 2019, 17(12), 710; https://doi.org/10.3390/md17120710 - 17 Dec 2019

Cited by 20 | Viewed by 2725

Abstract

Two new polyketides, 8-O-methylnodulisporin F (1) and nodulisporin H (2), two new naphthoquinones, 5-hydroxy-2-methoxy-6,7-dimethyl-1,4-naphthoquinone (3) and 5-hydroxy-2-methoxynaphtho[9–c]furan-1,4-dione (4), and a new naphthofuran 1,3,8-trimethoxynaphtho[9–c]furan (5), along with five [...] Read more.

Two new polyketides, 8-O-methylnodulisporin F (1) and nodulisporin H (2), two new naphthoquinones, 5-hydroxy-2-methoxy-6,7-dimethyl-1,4-naphthoquinone (3) and 5-hydroxy-2-methoxynaphtho[9–c]furan-1,4-dione (4), and a new naphthofuran 1,3,8-trimethoxynaphtho[9–c]furan (5), along with five known compounds 4-O-methyl eleutherol (6), 2-acetyl-7-methoxybenzofuran (7), (-)-orthosporin (8), diaporthin (9), and 6-hydroxymellein (10), were obtained from the EtOAc extract of the mangrove-derived fungus Daldinia eschscholtzii HJ004. The structures of the isolated compounds were elucidated by extensive NMR and MS analyses, while the absolute configurations of the stereogenic carbons were established based on experimental and calculated electronic circular dichroism spectra. Compounds 4 and 7 displayed a potent inhibitory activity against α-glucosidase with the IC₅₀ values of 5.7 and 1.1 μg/mL, respectively. Compounds 1 and 2 showed a moderate antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and Bacillus cereus, with minimum inhibitory concentration (MIC) values ranging from 6.25 to 12.5 μg/mL. Compound 3 exhibited antibacterial activity against B. cereus with the MIC value of 12.5 μg/mL. Full article

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12 pages, 2426 KiB

Open AccessArticle

Siderophore (from Synechococcus sp. PCC 7002)-Chelated Iron Promotes Iron Uptake in Caco-2 Cells and Ameliorates Iron Deficiency in Rats

by Xue Feng, Suisui Jiang, Fan Zhang, Runfang Wang, Yuanhui Zhao and Mingyong Zeng

Mar. Drugs 2019, 17(12), 709; https://doi.org/10.3390/md17120709 - 16 Dec 2019

Cited by 5 | Viewed by 2433

Abstract

Siderophores are iron chelators with low molecular weight secreted by microorganisms. Siderophores have the potential to become natural iron fortifiers. To explore the feasibility of the application of Synechococcus sp. PCC7002-derived siderophores as iron fortifiers, Synechococcus sp. PCC7002, as a carrier, was fermented [...] Read more.

Siderophores are iron chelators with low molecular weight secreted by microorganisms. Siderophores have the potential to become natural iron fortifiers. To explore the feasibility of the application of Synechococcus sp. PCC7002-derived siderophores as iron fortifiers, Synechococcus sp. PCC7002, as a carrier, was fermented to produce siderophores. The absorption mechanism and anemia intervention effect of siderophores-chelated iron (SCI) were studied through the polarized Caco-2 Cell monolayers and the rat model of iron-deficiency anemia, respectively. The results indicated that siderophores (from Synechococcus sp. PCC7002) had an enhancing effect on iron absorption in polarized Caco-2 cell monolayers. The main absorption site of SCI was duodenum with pH 5.5, and the absorption methods included endocytosis and DMT1, with endocytosis being dominant. The effect of sodium phytate on SCI was less than that of ferrous sulfate. Therefore, SCI could resist inhibitory iron absorption factors in polarized Caco-2 cell monolayers. SCI showed significantly higher relative bioavailability (133.58 ± 15.42%) than ferrous sulfate (100 ± 14.84%) and ferric citrate (66.34 ± 8.715%) in the rat model. Food intake, hemoglobin concentration, and hematocrit and serum iron concentration of rats improved significantly after Fe-repletion. Overall, this study indicated that siderophores derived from Synechococcus sp. PCC7002 could be an effective and feasible iron nutritive fortifier. Full article

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15 pages, 18538 KiB

Open AccessArticle

Pepsin-Soluble Collagen from the Skin of Lophius litulo: A Preliminary Study Evaluating Physicochemical, Antioxidant, and Wound Healing Properties

by Wen Zhang, Jiawen Zheng, Xiaoxiao Tian, Yunping Tang, Guofang Ding, Zuisu Yang and Huoxi Jin

Mar. Drugs 2019, 17(12), 708; https://doi.org/10.3390/md17120708 - 16 Dec 2019

Cited by 17 | Viewed by 3042

Abstract

The structure of pepsin-solubilized collagen (PSC) obtained from the skin of Lophius litulon was analyzed using the sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). SDS-PAGE results showed that PSC from Lophius litulon skin was [...] Read more.

The structure of pepsin-solubilized collagen (PSC) obtained from the skin of Lophius litulon was analyzed using the sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). SDS-PAGE results showed that PSC from Lophius litulon skin was collagen type I and had collagen-specific α1, α2, β, and γ chains. FTIR results indicated that the infrared spectrum of PSC ranged from 400 to 4000 cm⁻¹, with five main amide bands. SEM revealed the microstructure of PSC, which consisted of clear fibrous and porous structures. In vitro antioxidant studies demonstrated that PSC revealed the scavenging ability for 2,2-diphenyl-1-picrylhydrazyl (DPPH), HO·, O₂⁻·, and ABTS·. Moreover, animal experiments were conducted to evaluate the biocompatibility of PSC. The collagen sponge group showed a good biocompatibility in the skin wound model and may play a positive role in the progression of the healing process. The cumulative results suggest that collagen from the skin of Lophius litulon has potential applications in wound healing due to its good biocompatibility. Full article

(This article belongs to the Special Issue Marine Skeletal Biopolymers and Proteins, and Their Biomedical Application)

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10 pages, 880 KiB

Open AccessArticle

Plakinamine P, A Steroidal Alkaloid with Bactericidal Activity against Mycobacterium tuberculosis

by Carolina Rodrigues Felix, Jill C. Roberts, Priscilla L. Winder, Rashmi Gupta, M. Cristina Diaz, Shirley A. Pomponi, Amy E. Wright and Kyle H. Rohde

Mar. Drugs 2019, 17(12), 707; https://doi.org/10.3390/md17120707 - 16 Dec 2019

Cited by 6 | Viewed by 2510

Abstract

Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus Plakina revealed the [...] Read more.

Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus Plakina revealed the presence of a new steroidal alkaloid of the plakinamine class, which we have given the common name plakinamine P. Its structure is most similar to plakinamine L, which also has an acyclic side chain. Careful dissection of the nuclear magnetic resonance data, collected in multiple solvents, suggests that the dimethyl amino group at the 3 position is in an equatorial rather than axial position unlike previously reported plakinamines. Plakinamine P was bactericidal against M. tuberculosis, and exhibited moderate activity against other mycobacterial pathogens, such as M. abscessus and M. avium. Furthermore, it had low toxicity against J774 macrophages, yielding a selectivity index (SI, or IC₅₀/MIC) of 8.4. In conclusion, this work provides a promising scaffold to the tuberculosis drug discovery pipeline. Future work to determine the molecular target of this compound may reveal a pathway essential for M. tuberculosis survival during infection. Full article

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9 pages, 3056 KiB

Open AccessArticle

Fragilides U–W: New 11,20-Epoxybriaranes from the Sea Whip Gorgonian Coral Junceella fragilis

by Tung-Pin Su, Chien-Han Yuan, Yi-Ming Jhu, Bo-Rong Peng, Zhi-Hong Wen, Yu-Jen Wu, Tung-Ying Wu, Hong-Wen Liu and Ping-Jyun Sung

Mar. Drugs 2019, 17(12), 706; https://doi.org/10.3390/md17120706 - 15 Dec 2019

Cited by 7 | Viewed by 2184

Abstract

Three new 11,20-epoxybriaranes—fragilides U–W (1–3), as well as two known metabolites, junceellonoid D (4) and junceellin (5), were obtained from the octocoral Junceella fragilis. The structures of briaranes 1–3 were elucidated by [...] Read more.

Three new 11,20-epoxybriaranes—fragilides U–W (1–3), as well as two known metabolites, junceellonoid D (4) and junceellin (5), were obtained from the octocoral Junceella fragilis. The structures of briaranes 1–3 were elucidated by spectroscopic methods and briaranes 3 and 5 displayed inhibition effects on inducible nitric oxide synthase (iNOS) release from RAW264.7. Full article

(This article belongs to the Special Issue Bioactive Compounds from Coral Reef Organisms)

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10 pages, 2610 KiB

Open AccessArticle

Characterization of Carotenoid Biosynthesis in Newly Isolated Deinococcus sp. AJ005 and Investigation of the Effects of Environmental Conditions on Cell Growth and Carotenoid Biosynthesis

by Jun Young Choi, Kunjoong Lee and Pyung Cheon Lee

Mar. Drugs 2019, 17(12), 705; https://doi.org/10.3390/md17120705 - 14 Dec 2019

Cited by 11 | Viewed by 2773

Abstract

Our purpose was to characterize the structures of deinoxanthin from Deinococcus sp. AJ005. The latter is a novel reddish strain and was found to synthesize two main acyclic carotenoids: deinoxanthin and its derivative. The derivative (2-keto-deinoxanthin) contains a 2-keto functional group instead of [...] Read more.

Our purpose was to characterize the structures of deinoxanthin from Deinococcus sp. AJ005. The latter is a novel reddish strain and was found to synthesize two main acyclic carotenoids: deinoxanthin and its derivative. The derivative (2-keto-deinoxanthin) contains a 2-keto functional group instead of a 2-hydroxyl group on a β-ionone ring. A deinoxanthin biosynthesis pathway of Deinococcus sp. AJ005 involving eight putative enzymes was proposed according to genome annotation analysis and chemical identification of deinoxanthin. Optimal culture pH and temperature for Deinococcus sp. AJ005 growth were pH 7.4 and 20 °C. Sucrose as a carbon source significantly enhanced the cell growth in comparison with glucose, glycerol, maltose, lactose, and galactose. When batch fermentation was performed in a bioreactor containing 40g/L sucrose, total carotenoid production was 650% higher than that in a medium without sucrose supplementation. The culture conditions found in this study should provide the basis for the development of fermentation strategies for the production of deinoxanthin and of its derivative by means of Deinococcus sp. AJ005. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments)

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6 pages, 636 KiB

Open AccessArticle

Stable Tetrodotoxin Production by Bacillus sp. Strain 1839

by Daria I. Melnikova, Anna E. Vlasenko and Timur Yu. Magarlamov

Mar. Drugs 2019, 17(12), 704; https://doi.org/10.3390/md17120704 - 13 Dec 2019

Cited by 16 | Viewed by 3147

Abstract

For the first time, tetrodotoxin (TTX) was detected in a bacterial strain after five years of cultivation in laboratory conditions since its isolation from the animal host. A reliable method suitable for bacterial samples, high-performance liquid chromatography with tandem mass spectrometry, was used [...] Read more.

For the first time, tetrodotoxin (TTX) was detected in a bacterial strain after five years of cultivation in laboratory conditions since its isolation from the animal host. A reliable method suitable for bacterial samples, high-performance liquid chromatography with tandem mass spectrometry, was used for toxin detection in spore and vegetative cultures of Bacillus sp. 1839. TTX was detected in a spore culture of the strain. Full article

(This article belongs to the Special Issue Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection)

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19 pages, 3516 KiB

Open AccessArticle

Isolation, Optimization of Fermentation Conditions, and Characterization of an Exopolysaccharide from Pseudoalteromonas agarivorans Hao 2018

by Lujiang Hao, Wenlin Liu, Kai Liu, Kai Shan, Chunlei Wang, Chenxiang Xi, Jianbang Liu, Qiuping Fan, Xiaofei Zhang, Xiaoping Lu, Yanrui Xu, RuiWen Cao, Yaohong Ma, Lan Zheng and Bo Cui

Mar. Drugs 2019, 17(12), 703; https://doi.org/10.3390/md17120703 - 13 Dec 2019

Cited by 15 | Viewed by 2947

Abstract

In recent years, the wide application of exopolysaccharides (EPSs) in food, cosmetics, medicine, and other fields has drawn tremendous attention. In this study, an EPS produced by Pseudoalteromonas agarivorans Hao 2018 was isolated and purified, and its fermentation conditions were optimized. Its structure [...] Read more.

In recent years, the wide application of exopolysaccharides (EPSs) in food, cosmetics, medicine, and other fields has drawn tremendous attention. In this study, an EPS produced by Pseudoalteromonas agarivorans Hao 2018 was isolated and purified, and its fermentation conditions were optimized. Its structure and biological functions were also studied. The purity and molecular weight of EPS were determined by high performance liquid chromatography (HPLC), and the EPS exhibited a number average of 2.26 × 10⁵ and a weight average of 2.84 × 10⁵. EPS has good adsorption for Cu²⁺ and Pb²⁺. The adsorption rates can reach up to 69.79% and 82.46%, respectively. The hygroscopic property of EPS was higher than that of chitosan, but slightly lower than that of sodium hyaluronate. However, the water-retaining activity of EPS was similar to that of chitosan and sodium hyaluronate. EPS has strong ability to scavenge free radicals, including OH radical and O²⁻ radical. Further, its activity on O²⁻ radicals has similarities with that of vitamin C. EPS has broad application prospects in many fields, such as cosmetics, environmental protection. Full article

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16 pages, 4866 KiB

Open AccessArticle

Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs

by Guanyu Yang, Lin Jin, Dongxiao Zheng, Xiaoliang Tang, Junwei Yang, Lingxuan Fan and Xi Xie

Mar. Drugs 2019, 17(12), 702; https://doi.org/10.3390/md17120702 - 12 Dec 2019

Cited by 28 | Viewed by 3834

Abstract

As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation [...] Read more.

As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation and acetylation status, regulated by Akt and Sirt1, a lysine deacetylase. Our study aimed to investigate whether fucoxanthin could alleviate oxidative stress and fibrosis via FoxO3α in DN and whether Akt and Sirt1 were involved. We found that in GMCs cultured in HG, fucoxanthin treatment significantly reduced the expression of FN and collagen IV, as well as reactive oxygen species generation, suggesting that fucoxanthin is beneficial to alleviate both fibrosis and oxidative stress in DN. In addition, we found that fucoxanthin decreased the phosphorylation and acetylation level of FoxO3α, reversed the protein level of FoxO3α inhibited by HG, and then promoted the nuclear transport of FoxO3α. Besides, fucoxanthin promoted the expression of manganese superoxide dismutase, a downstream target of FoxO3α. Furthermore, we found that fucoxanthin reversed the activation of Akt and inhibition of Sirt1. However, the enhancement of fucoxanthin in FoxO3α expression and nuclear transport was significantly decreased by pretreatment with Akt activator SC79 or Sirt1 inhibitor EX527. In summary, our study explored fucoxanthin alleviated oxidative stress and fibrosis induced by HG through Akt/Sirt1/FoxO3α signaling in GMCs, suggesting fucoxanthin is a potential therapeutic strategy for DN. Full article

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21 pages, 4581 KiB

Open AccessArticle

A Versatile and Robust Serine Protease Inhibitor Scaffold from Actinia tenebrosa

by Xingchen Chen, Darren Leahy, Jessica Van Haeften, Perry Hartfield, Peter J. Prentis, Chloé A. van der Burg, Joachim M. Surm, Ana Pavasovic, Bruno Madio, Brett R. Hamilton, Glenn F. King, Eivind A. B. Undheim, Maria Brattsand and Jonathan M. Harris

Mar. Drugs 2019, 17(12), 701; https://doi.org/10.3390/md17120701 - 12 Dec 2019

Cited by 9 | Viewed by 3982

Abstract

Serine proteases play pivotal roles in normal physiology and a spectrum of patho-physiological processes. Accordingly, there is considerable interest in the discovery and design of potent serine protease inhibitors for therapeutic applications. This led to concerted efforts to discover versatile and robust molecular [...] Read more.

Serine proteases play pivotal roles in normal physiology and a spectrum of patho-physiological processes. Accordingly, there is considerable interest in the discovery and design of potent serine protease inhibitors for therapeutic applications. This led to concerted efforts to discover versatile and robust molecular scaffolds for inhibitor design. This investigation is a bioprospecting study that aims to isolate and identify protease inhibitors from the cnidarian Actinia tenebrosa. The study isolated two Kunitz-type protease inhibitors with very similar sequences but quite divergent inhibitory potencies when assayed against bovine trypsin, chymostrypsin, and a selection of human sequence-related peptidases. Homology modeling and molecular dynamics simulations of these inhibitors in complex with their targets were carried out and, collectively, these methodologies enabled the definition of a versatile scaffold for inhibitor design. Thermal denaturation studies showed that the inhibitors were remarkably robust. To gain a fine-grained map of the residues responsible for this stability, we conducted in silico alanine scanning and quantified individual residue contributions to the inhibitor’s stability. Sequences of these inhibitors were then used to search for Kunitz homologs in an A. tenebrosa transcriptome library, resulting in the discovery of a further 14 related sequences. Consensus analysis of these variants identified a rich molecular diversity of Kunitz domains and expanded the palette of potential residue substitutions for rational inhibitor design using this domain. Full article

(This article belongs to the Special Issue Anthozoan Toxins: Using New Approaches to Understand Their Composition, Distribution, and Function)

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17 pages, 1841 KiB

Open AccessArticle

Genome-Wide Identification and Characterization of SODs in Zhikong Scallop Reveals Gene Expansion and Regulation Divergence after Toxic Dinoflagellate Exposure

by Shanshan Lian, Liang Zhao, Xiaogang Xun, Jiarun Lou, Moli Li, Xu Li, Shi Wang, Lingling Zhang, Xiaoli Hu and Zhenmin Bao

Mar. Drugs 2019, 17(12), 700; https://doi.org/10.3390/md17120700 - 12 Dec 2019

Cited by 24 | Viewed by 3259

Abstract

As filter-feeding animals mainly ingesting microalgae, bivalves could accumulate paralytic shellfish toxins (PSTs) produced by harmful algae through diet. To protect themselves from the toxic effects of PSTs, especially the concomitant oxidative damage, the production of superoxide dismutase (SOD), which is the only [...] Read more.

As filter-feeding animals mainly ingesting microalgae, bivalves could accumulate paralytic shellfish toxins (PSTs) produced by harmful algae through diet. To protect themselves from the toxic effects of PSTs, especially the concomitant oxidative damage, the production of superoxide dismutase (SOD), which is the only eukaryotic metalloenzyme capable of detoxifying superoxide, may assist with toxin tolerance in bivalves. To better understand this process, in the present study, we performed the first systematic analysis of SOD genes in bivalve Chlamys farreri, an important aquaculture species in China. A total of six Cu/Zn-SODs (SOD1-6) and two Mn-SODs (SOD7, SOD8) were identified in C. farreri, with gene expansion being revealed in Cu/Zn-SODs. In scallops exposed to two different PSTs-producing dinoflagellates, Alexandrium minutum and A. catenella, expression regulation of SOD genes was analyzed in the top ranked toxin-rich organs, the hepatopancreas and the kidney. In hepatopancreas, which mainly accumulates the incoming PSTs, all of the six Cu/Zn-SODs showed significant alterations after A. minutum exposure, with SOD1, 2, 3, 5, and 6 being up-regulated, and SOD4 being down-regulated, while no significant change was detected in Mn-SODs. After A. catenella exposure, up-regulation was observed in SOD2, 4, 6, and 8, and SOD7 was down-regulated. In the kidney, where PSTs transformation occurs, SOD4, 5, 6, and 8 were up-regulated, and SOD7 was down-regulated in response to A. minutum feeding. After A. catenella exposure, all the Cu/Zn-SODs except SOD1 were up-regulated, and SOD7 was down-regulated in kidney. Overall, in scallops after ingesting different toxic algae, SOD up-regulation mainly occurred in the expanded Cu/Zn-SOD group, and SOD6 was the only member being up-regulated in both toxic organs, which also showed the highest fold change among all the SODs, implying the importance of SOD6 in protecting scallops from the stress of PSTs. Our results suggest the diverse function of scallop SODs in response to the PST-producing algae challenge, and the expansion of Cu/Zn-SODs might be implicated in the adaptive evolution of scallops or bivalves with respect to antioxidant defense against the ingested toxic algae. Full article

(This article belongs to the Special Issue Chemical Defense in Marine Organisms)

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17 pages, 2582 KiB

Open AccessArticle

Pharmaceutical Development and Safety Evaluation of a GMP-Grade Fucoidan for Molecular Diagnosis of Cardiovascular Diseases

by Cédric Chauvierre, Rachida Aid-Launais, Joël Aerts, Frédéric Chaubet, Murielle Maire, Lucas Chollet, Lydia Rolland, Roberta Bonafé, Silvia Rossi, Simona Bussi, Claudia Cabella, Laszlo Dézsi, Tamas Fülöp, Janos Szebeni, Youssef Chahid, Kang H. Zheng, Erik S. G. Stroes, Dominique Le Guludec, François Rouzet and Didier Letourneur

Mar. Drugs 2019, 17(12), 699; https://doi.org/10.3390/md17120699 - 12 Dec 2019

Cited by 26 | Viewed by 3540

Abstract

The adhesion molecule P-selectin is present on the cell surface of both activated endothelium and activated platelets. The present study describes the pharmaceutical development, safety evaluation, and preclinical efficacy of a micro-dosed radiotracer. The macromolecular nanoscale assembly consisted of a natural compound made [...] Read more.

The adhesion molecule P-selectin is present on the cell surface of both activated endothelium and activated platelets. The present study describes the pharmaceutical development, safety evaluation, and preclinical efficacy of a micro-dosed radiotracer. The macromolecular nanoscale assembly consisted of a natural compound made of a sulfated fucose-rich polysaccharides (fucoidan) and a radionuclide (technetium-99m) for the detection of P-selectin expression in cardiovascular diseases. After extraction and fractionation from brown seaweeds, the good manufacturing practice (GMP) production of a low molecular weight (LMW) fucoidan of 7 kDa was achieved and full physicochemical characterization was performed. The regulatory toxicology study in rats of the GMP batch of LMW fucoidan revealed no adverse effects up to 400 μg/kg (×500 higher than the expected human dose) and pseudoallergy was not seen as well. In a myocardial ischemia-reperfusion model in rats, the GMP-grade LMW fucoidan labeled with technetium-99m detected P-selectin upregulation in vivo. The present study supports the potential of using ^99mTc-fucoidan as an imaging agent to detect activated endothelium in humans. Full article

(This article belongs to the Special Issue Vascular Bioactivities of Marine Natural Products)

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9 pages, 1703 KiB

Open AccessArticle

Enhypyrazinones A and B, Pyrazinone Natural Products from a Marine-Derived Myxobacterium Enhygromyxa sp.

by Fan Zhang, Doug R. Braun, Scott R. Rajski, Don DeMaria and Tim S. Bugni

Mar. Drugs 2019, 17(12), 698; https://doi.org/10.3390/md17120698 - 12 Dec 2019

Cited by 10 | Viewed by 2570

Abstract

To date, studies describing myxobacterial secondary metabolites have been relatively scarce in comparison to those addressing actinobacterial secondary metabolites. This realization suggests the immense potential of myxobacteria as an intriguing source of secondary metabolites with unusual structural features and a wide array of [...] Read more.

To date, studies describing myxobacterial secondary metabolites have been relatively scarce in comparison to those addressing actinobacterial secondary metabolites. This realization suggests the immense potential of myxobacteria as an intriguing source of secondary metabolites with unusual structural features and a wide array of biological activities. Marine-derived myxobacteria are especially attractive due to their unique biosynthetic gene clusters, although they are more difficult to handle than terrestrial myxobacteria. Here, we report the discovery of two new pyrazinone-type molecules, enhypyrazinones A and B, from a marine-derived myxobacterium Enhygromyxa sp. Their structures were elucidated by HRESIMS and comprehensive NMR data analyses. Compounds 1 and 2, which contain a rare trisubstituted-pyrazinone core, represent a unique class of molecules from Enhygromyxa sp. Full article

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14 pages, 4154 KiB

Open AccessArticle

Effect of Oral Administration of Active Peptides of Pinctada Martensii on the Repair of Skin Wounds

by Faming Yang, Xiaoming Qin, Ting Zhang, Chaohua Zhang and Haisheng Lin

Mar. Drugs 2019, 17(12), 697; https://doi.org/10.3390/md17120697 - 12 Dec 2019

Cited by 17 | Viewed by 3749

Abstract

Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of active peptides (APs) [...] Read more.

Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of active peptides (APs) of the mantle of Pinctada martensii on wound healing. After physicochemical analysis of amino acids and mass spectrometry of APs, the effect of APs on promoting healing was studied through a whole cortex wound model on the back of mice for 18 consecutive days. The results showed that APs consisted of polypeptides with molecular weights in the range 302.17–2936.43 Da. The content of polypeptides containing 2–15 amino acids accounted for 73.87%, and the hydrophobic amino acids accounted for 56.51%. Results of in vitro experimentation showed that mice in APs-L group which were fed a low dose of APs (0.5 g/kg bw) had a shortened epithelialization time due to a shortening inflammatory period (p < 0.05). Mechanistically, this relied on its specific ability to promote the proliferation of CD31, FGF and EGF which accelerated the percentage of wound closure. Moreover, the APs-L group mice had enhanced collagen synthesis and increased type III collagen content in their wounds through a TGF-β/Smad signaling pathway (p > 0.05). Consequently, scar formation was inhibited and wound healing efficiency was significantly improved. These results show that the APs of Pinctada martensii promote dermal wound healing in mice and have tremendous potential for development and utilization in skin wound healing. Full article

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14 pages, 3183 KiB

Open AccessArticle

Discovery of Geranylgeranyl Pyrophosphate Synthase (GGPPS) Paralogs from Haematococcus pluvialis Based on Iso-Seq Analysis and Their Function on Astaxanthin Biosynthesis

by Danqiong Huang, Wenfu Liu, Anguo Li, Chaogang Wang and Zhangli Hu

Mar. Drugs 2019, 17(12), 696; https://doi.org/10.3390/md17120696 - 12 Dec 2019

Cited by 12 | Viewed by 3301

Abstract

Haematococcus pluvialis is widely distributed in the world and well known as the richest natural source of astaxanthin that is a strong antioxidant with excellent commercial value. The pathway of astaxanthin biosynthesis in H. pluvialis has been documented as an enzymatic reaction. Several [...] Read more.

Haematococcus pluvialis is widely distributed in the world and well known as the richest natural source of astaxanthin that is a strong antioxidant with excellent commercial value. The pathway of astaxanthin biosynthesis in H. pluvialis has been documented as an enzymatic reaction. Several enzymes have been reported, but their isoforms or homologs have not been investigated genome-wide. To better understand the astaxanthin biosynthesis pathway in H. pluvialis, eight candidates of the geranylgeranyl pyrophosphate synthase gene (HpGGPPS) predicted from Iso-seq data were isolated in this study. The length of coding region of these candidates varied from 960 bp to 1272 bp, composing of 7–9 exons. The putative amino acids of all candidates composed the signature domain of GGPPS gene. However, the motifs in the domain region are varied, indicating different bio-functions. Phylogenetic analysis revealed eight candidates can be clustered into three groups. Only two candidates in Group1 encode the synthase participating in the astaxanthin formation. The yield of astaxanthin from these two candidates, 7.1 mg/g (DW) and 6.5 mg/g (DW) respectively, is significant higher than that from CrtE (2.4 mg/g DW), a GGPPS gene from Pantoea ananatis. This study provides a potential productive pathway for astaxanthin synthesis. Full article

(This article belongs to the Special Issue Synthetic and Biosynthetic Approaches to Marine Natural Products)

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16 pages, 4251 KiB

Open AccessArticle

A Cold-Adapted Chitinase-Producing Bacterium from Antarctica and Its Potential in Biocontrol of Plant Pathogenic Fungi

by Kezhen Liu, Haitao Ding, Yong Yu and Bo Chen

Mar. Drugs 2019, 17(12), 695; https://doi.org/10.3390/md17120695 - 10 Dec 2019

Cited by 31 | Viewed by 4384

Abstract

To obtain chitinase-producing microorganisms with high chitinolytic activity at low temperature, samples collected from Fildes Peninsula in Antarctica were used as sources for bioprospecting of chitinolytic microorganisms. A cold-adapted strain, designated as GWSMS-1, was isolated from marine sediment and further characterized as Pseudomonas [...] Read more.

To obtain chitinase-producing microorganisms with high chitinolytic activity at low temperature, samples collected from Fildes Peninsula in Antarctica were used as sources for bioprospecting of chitinolytic microorganisms. A cold-adapted strain, designated as GWSMS-1, was isolated from marine sediment and further characterized as Pseudomonas. To improve the chitinase production, one-factor-at-a-time and orthogonal test approaches were adopted to optimize the medium components and culture conditions. The results showed that the highest chitinolytic activity (6.36 times higher than that before optimization) was obtained with 95.41 U L⁻¹ with 15 g L⁻¹ of glucose, 1 g L⁻¹ of peptone, 15 g L⁻¹ of colloid chitin and 0.25 g L⁻¹ of magnesium ions contained in the medium, cultivated under pH 7.0 and a temperature of 20 °C. To better understand the application potential of this strain, the enzymatic properties and the antifungal activity of the crude chitinase secreted by the strain were further investigated. The crude enzyme showed the maximum catalytic activity at 35 °C and pH 4.5, and it also exhibited excellent low-temperature activity, which still displayed more than 50% of its maximal activity at 0 °C. Furthermore, the crude chitinase showed significant inhibition of fungi Verticillium dahlia CICC 2534 and Fusarium oxysporum f. sp. cucumerinum CICC 2532, which can cause cotton wilt and cucumber blight, respectively, suggesting that strain GWSMS-1 could be a competitive candidate for biological control in agriculture, especially at low temperature. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments)

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16 pages, 3199 KiB

Open AccessArticle

Inhibitory Effect of Depolymerized Sulfated Galactans from Marine Red Algae on the Growth and Adhesion of Diarrheagenic Escherichia coli

by Yixiang Liu, Wenqiang Liu, Yanbo Wang, Yu Ma, Ling Huang, Chao Zou, Donghui Li, Min-Jie Cao and Guang-Ming Liu

Mar. Drugs 2019, 17(12), 694; https://doi.org/10.3390/md17120694 - 10 Dec 2019

Cited by 16 | Viewed by 2975

Abstract

Active polysaccharides as safe and natural polymers against bacterial diarrhea have been reconsidered as an alternative to antibiotics. This work investigated the inhibiting effect of depolymerized sulfated galactans from Eucheuma serra and Gracilaria verrucosa on the growth and adhesion of diarrheagenic enterotoxigenic Escherichia [...] Read more.

Active polysaccharides as safe and natural polymers against bacterial diarrhea have been reconsidered as an alternative to antibiotics. This work investigated the inhibiting effect of depolymerized sulfated galactans from Eucheuma serra and Gracilaria verrucosa on the growth and adhesion of diarrheagenic enterotoxigenic Escherichia coli (ETEC) K88. Results showed that the sulfated polysaccharides with molecular weight distribution ≤20.0 kDa exhibited antibacterial activity against ETEC K88. A structure–activity study revealed that the anti-ETEC K88 activity of sulfated polysaccharides is strictly determined by their molecular weight distribution, sulfate group content, and monosaccharide composition. In addition, the promoted nucleic acid release and the fluorescence quenching of membrane proteins were observed after the treatment with selected polysaccharides. Scanning electron microscopy further confirmed that the depolymerized sulfated galactans can effectively inhibit ETEC K88 adhesion. In conclusion, depolymerized sulfated galactans exhibited an inhibitory effect on the growth and adhesion of ETEC K88. 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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21 pages, 6730 KiB

Open AccessArticle

Epinecidin-1 Protects against Methicillin Resistant Staphylococcus aureus Infection and Sepsis in Pyemia Pigs

by Han-Ning Huang, Chieh-Yu Pan, Bor-Chyuan Su, Hung-Yi Wu and Jyh-Yih Chen

Mar. Drugs 2019, 17(12), 693; https://doi.org/10.3390/md17120693 - 09 Dec 2019

Cited by 6 | Viewed by 2978

Abstract

Methicillin resistant Staphylococcus aureus (MRSA) may be found on the skin, nose, and throats of long-term hospitalized patients. While MRSA infections are usually minor, serious infections and death may occur in immunocompromised or diabetic patients, or after exposure of MRSA to blood. This [...] Read more.

Methicillin resistant Staphylococcus aureus (MRSA) may be found on the skin, nose, and throats of long-term hospitalized patients. While MRSA infections are usually minor, serious infections and death may occur in immunocompromised or diabetic patients, or after exposure of MRSA to blood. This report demonstrates that the antimicrobial peptide (AMP) epinecidin-1 (Epi-1) efficiently protects against MRSA infection in a pyemia pig model. We first found that Epi-1 exhibits bactericidal activity against MRSA. Next, pharmacokinetic analysis revealed that Epi-1 was stable in serum for 4 h after injection, followed by a gradual decrease. This pharmacokinetic profile suggested Epi-1 may bind serum albumin, which was confirmed in vitro. Harmful effects were not observed for doses up to 100 mg/kg body weight in pigs. When Epi-1 was supplied as a curative agent 30 min post-infection, MRSA-induced abnormalities in blood uric acid (UA), blood urea nitrogen (BUN), creatine (CRE), GOT, and GPT levels were restored to normal levels. We further showed that the bactericidal activity of Epi-1 was higher than that of the antibiotic drug vancomycin. Epi-1 significantly decreased MRSA counts in the blood, liver, kidney, heart, and lungs of infected pigs. Elevated levels of serum C reactive protein (CRP), proinflammatory cytokine IL6, IL1β, and TNFα were also attenuated by Epi-1 treatment. Moreover, the MRSA genes, enterotoxin (et)-A, et-B, intrinsic methicillin resistance A (mecA), and methicillin resistance factor A (femA), were significantly reduced or abolished in MRSA-infected pigs after treatment with Epi-1. Hematoxylin and eosin staining of heart, liver, lung, and kidney sections indicated that Epi-1 attenuated MRSA toxicity in infected pigs. A survival study showed that the pyemia pigs infected with MRSA alone died within a week, whereas the pigs post-treated with 2.5 mg/kg Epi-1 were completely protected against death. The present investigation, thus, demonstrates that Epi-1 effectively protects pyemia pigs against pathogenic MRSA without major toxic side effects. Full article

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24 pages, 8561 KiB

Open AccessArticle

Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole

by Marta Szekalska, Magdalena Wróblewska, Monika Trofimiuk, Anna Basa and Katarzyna Winnicka

Mar. Drugs 2019, 17(12), 692; https://doi.org/10.3390/md17120692 - 09 Dec 2019

Cited by 34 | Viewed by 4276

Abstract

Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and [...] Read more.

Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and seem to be a very promising alternative to conventional oral formulations. Hence, in this study, mucoadhesive buccal films based on the alginate and its oligosaccharide oligomer composed predominantly of mannuronic acid for the administration of posaconazole-antifungal drug from the azole group were developed. As the polymer gelation method, a relatively new freeze-thaw technique was chosen. All prepared formulations were examined for pharmaceutical tests, swelling, mechanical, and mucoadhesive properties. In addition, the influence of sodium alginate (ALG) and alginate oligosaccharides (OLG) on POS antifungal activity on Candida species was performed. It was observed that film formulation containing 1% ALG and 1% OLG (F2) was characterized by optimal mucoadhesive and swelling properties and prolonged drug release up to 5 h. Additionally, it was shown that OLG affected the growth reduction of all tested Candida spp. The obtained data has opened the way for future research for developing OLG-based dosage forms, which might increase the activity of antifungal drugs. Full article

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

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10 pages, 1356 KiB

Open AccessArticle

One-Step Preparative Separation of Phytosterols from Edible Brown Seaweed Sargassum horneri by High-Speed Countercurrent Chromatography

by Menglu Xia, Chunping Liu, Lei Gao and Yanbin Lu

Mar. Drugs 2019, 17(12), 691; https://doi.org/10.3390/md17120691 - 09 Dec 2019

Cited by 12 | Viewed by 3437

Abstract

Sargassum horneri, a sargassaceae brown alga, is one of the main species in the subtidal seaweeds flora extensively distributed in the Yellow and East China Sea. It has been proven that the phytosterols are an important class of bioactive substances in S. [...] Read more.

Sargassum horneri, a sargassaceae brown alga, is one of the main species in the subtidal seaweeds flora extensively distributed in the Yellow and East China Sea. It has been proven that the phytosterols are an important class of bioactive substances in S. horneri. In this work, a counter-current chromatography approach is proposed for preparative separation of phytol and two analogue sterols from a crude extract of S. horneri. A two-phase solvent system composed of n-hexane-acetonitrile-methanol (5:5:6, v/v) was selected and optimized. The effects of rotary speed and flow rate on the retention of the stationary phase were carefully studied. Under the optimum conditions, phytol and two analogue sterols, fucosterol and saringosterol, were baseline separated, producing 19.8 mg phytol, 23.7 mg fucosterol, and 3.1 mg saringosterol from 300 mg of crude S. horneri extract in one-step separation. The purities of three target compounds were all above 85%. The structures of phytol and two sterols were identified by nuclear magnetic resonance spectroscopy. Full article

(This article belongs to the Special Issue Advancements in Purification, Isolation and Chemical Profiling to Expedite the Discovery of Marine Natural Products)

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12 pages, 2267 KiB

Open AccessArticle

In Vivo Hepatoprotective Effects of a Peptide Fraction from Krill Protein Hydrolysates against Alcohol-Induced Oxidative Damage

by Soo Yeon Park, Ilekuttige Priyan Shanura Fernando, Eui Joeng Han, Min Ju Kim, Kyungsook Jung, Dong-Soo Kang, Chang-Bum Ahn and Ginnae Ahn

Mar. Drugs 2019, 17(12), 690; https://doi.org/10.3390/md17120690 - 07 Dec 2019

Cited by 30 | Viewed by 3298

Abstract

Background: Krill (Euphausia superba) represent the largest animal biomass on earth, and are a rich source of high-quality protein with essential amino acids. Krill-derived peptides are renowned for their antioxidant activities. Hence, these peptides may have protective effects against oxidative stress. [...] Read more.

Background: Krill (Euphausia superba) represent the largest animal biomass on earth, and are a rich source of high-quality protein with essential amino acids. Krill-derived peptides are renowned for their antioxidant activities. Hence, these peptides may have protective effects against oxidative stress. Alcoholic liver disease is a prevalent cause of death worldwide. The present study explores the hepatoprotective effects of krill peptide hydrolysate fractions against ethanol-induced liver damage in BALB/c mice. Methods: Hydrolysis was carried out by mimicking the gastrointestinal digestion environment and the filtrate was fractionated based on molecular weight (<1 kDa, 1–3 kDa, and >3 kDa). The 1–3 kDa fraction (KPF), which indicated the highest antioxidant effect, was further investigated for its effect on weight and survival rate increase in mice and its influence on serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels were measured, followed by Nrf2 and HO-1 expression. Histopathology studies were conducted to assess hepatic tissue damage. Results: KPF enhanced the weight and survival rate of mice while reducing serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, KPF upregulated SOD, CAT, and GPx in liver tissues, while downregulating tumor necrosis factor α and interleukin-6 mRNA expression. KPF further increased Nrf2 and HO-1 expression and suppressed ethanol-induced apoptotic proteins in the liver. Histopathology of KPF-treated mice showed less hepatic tissue damage compared to ethanol-treated mice. Conclusions: Hydrolysates and bioactive peptides prepared from krill can be employed as functional foods to enhance liver function and health. Further investigations of KPF could lead to the development of functional foods. Full article

(This article belongs to the Special Issue Marine Immunomodulators)

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20 pages, 1758 KiB

Open AccessReview

Innovative Green Technologies of Intensification for Valorization of Seafood and Their By-Products

by Fadila Al Khawli, Mirian Pateiro, Rubén Domínguez, José M. Lorenzo, Patricia Gullón, Katerina Kousoulaki, Emilia Ferrer, Houda Berrada and Francisco J. Barba

Mar. Drugs 2019, 17(12), 689; https://doi.org/10.3390/md17120689 - 06 Dec 2019

Cited by 151 | Viewed by 15537

Abstract

The activities linked to the fishing sector generate substantial quantities of by-products, which are often discarded or used as low-value ingredients in animal feed. However, these marine by-products are a prominent potential good source of bioactive compounds, with important functional properties that can [...] Read more.

The activities linked to the fishing sector generate substantial quantities of by-products, which are often discarded or used as low-value ingredients in animal feed. However, these marine by-products are a prominent potential good source of bioactive compounds, with important functional properties that can be isolated or up-concentrated, giving them an added value in higher end markets, as for instance nutraceuticals and cosmetics. This valorization of fish by-products has been boosted by the increasing awareness of consumers regarding the relationship between diet and health, demanding new fish products with enhanced nutritional and functional properties. To obtain fish by-product-derived biocompounds with good, functional and acceptable organoleptic properties, the selection of appropriate extraction methods for each bioactive ingredient is of the outmost importance. In this regard, over the last years, innovative alternative technologies of intensification, such as ultrasound-assisted extraction (UAE) and supercritical fluid extraction (SFE), have become an alternative to the conventional methods in the isolation of valuable compounds from fish and shellfish by-products. Innovative green technologies present great advantages to traditional methods, preserving and even enhancing the quality and the extraction efficiency, as well as minimizing functional properties’ losses of the bioactive compounds extracted from marine by-products. Besides their biological activities, bioactive compounds obtained by innovative alternative technologies can enhance several technological properties of food matrices, enabling their use as ingredients in novel foods. This review is focusing on analyzing the principles and the use of UAE and SFE as emerging technologies to valorize seafoods and their by-products. Full article

(This article belongs to the Special Issue Aquaculture Wastes and By-products as Source of High Added Value Compounds: Extraction, and Health Aspects)

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19 pages, 1454 KiB

Open AccessReview

Potential Use of Seaweed Bioactive Compounds in Skincare—A Review

by Valentina Jesumani, Hong Du, Muhammad Aslam, Pengbing Pei and Nan Huang

Mar. Drugs 2019, 17(12), 688; https://doi.org/10.3390/md17120688 - 06 Dec 2019

Cited by 103 | Viewed by 22658

Abstract

Modern lifestyles have developed new attention on appearance and personal care which attract a huge number of consumers towards cosmetic products. The demand for a skincare product with natural ingredients is rapidly increasing. Seaweeds are major resources for in-demand active compounds with a [...] Read more.

Modern lifestyles have developed new attention on appearance and personal care which attract a huge number of consumers towards cosmetic products. The demand for a skincare product with natural ingredients is rapidly increasing. Seaweeds are major resources for in-demand active compounds with a wide variety of applications. The use of seaweed-derived ingredients in cosmetic products has increased in recent years as many scientific studies have proved the potential skincare properties of seaweed bioactive compounds. This review emphasizes possible skincare properties of seaweed bioactive compounds. The review outlines the mechanism involved in skin problems including hyperpigmentation, premature skin aging, and acne in the first part while the second part focuses on the promising application of seaweeds in skin protection by highlighting the bioactive compound responsible for their bioactivity. Full article

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

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9 pages, 717 KiB

Open AccessArticle

The Pharmacokinetics of Fucoidan after Topical Application to Rats

by Olga N. Pozharitskaya, Alexander N. Shikov, Ekaterina D. Obluchinskaya and Heikki Vuorela

Mar. Drugs 2019, 17(12), 687; https://doi.org/10.3390/md17120687 - 06 Dec 2019

Cited by 45 | Viewed by 5746

Abstract

Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this [...] Read more.

Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this study, an ointment (OF) containing 15% fucoidan was topically applied to rats at the doses of 50–150 mg/g. The anti-Xa activity was selected as the biomarker, and the amidolytic assay method was validated and applied for pharmacokinetic studies of fucoidan. Fucoidan in OF penetrated the skin and distributed into the skin, striated muscle, and plasma with AUC_0–48 = 0.94 μg·h/g, 2.22 μg·h/g, and 1.92 µg·h/mL, respectively. The longest half-life for fucoidan was observed in plasma, then in striated muscle and skin. It was found that the pharmacokinetics of fucoidan after topical OF application was linear, in the range of 50–150 mg/kg. No accumulation of fucoidan in plasma was observed after repeated topical applications of 100 mg/kg during five days. Our results support the rationality of topical application of formulations with fucoidan. Full article

(This article belongs to the Special Issue Pharmacokinetic Research of Marine Drugs)

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14 pages, 3859 KiB

Open AccessArticle

Cytotoxic Polyketides Isolated from the Deep-Sea-Derived Fungus Penicillium chrysogenum MCCC 3A00292

by Siwen Niu, Manli Xia, Mingliang Chen, Xiupian Liu, Zengpeng Li, Yunchang Xie, Zongze Shao and Gaiyun Zhang

Mar. Drugs 2019, 17(12), 686; https://doi.org/10.3390/md17120686 - 05 Dec 2019

Cited by 22 | Viewed by 3505

Abstract

The chemical examination of the solid cultures of the deep-sea-derived fungus Penicillium chrysogenum MCCC 3A00292 resulted in the isolation of three new versiol-type analogues, namely peniciversiols A–C (1–3), and two novel lactone derivatives, namely penicilactones A and B ( [...] Read more.

The chemical examination of the solid cultures of the deep-sea-derived fungus Penicillium chrysogenum MCCC 3A00292 resulted in the isolation of three new versiol-type analogues, namely peniciversiols A–C (1–3), and two novel lactone derivatives, namely penicilactones A and B (6 and 7), along with 11 known polyketides. The planar structures of the new compounds were determined by the comprehensive analyses of the high-resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) data, while their absolute configurations were resolved on the basis of comparisons of the experimental electronic circular dichroism (ECD) spectra with the calculated ECD data. Compound 1 is the second example of versiols featuring a 2,3-dihydropyran-4-one ring. Additionally, compounds 6 and 7 are the first representatives of γ-lactone derivatives constructed by a 1,3-dihydroxy-5-methylbenzene unit esterifying with the α-methyl-γ-hydroxy-γ-acetic acid α,β-unsaturated-γ-lactone moiety and α-hydroxy-γ-methyl-γ-acetic acid α,β-unsaturated-γ-lactone unit, respectively. All of the isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines of BIU-87, ECA109, BEL-7402, PANC-1, and Hela-S3. Compound 1 exhibited a selective inhibitory effect against the BIU-87 cell line (IC₅₀ = 10.21 μM), while compounds 4, 5, 8, and 12–16 showed inhibitory activities against the ECA109, BIU-87, and BEL-7402 cell lines with the IC₅₀ values ranging from 7.70 to > 20 μM. Full article

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12 pages, 1627 KiB

Open AccessArticle

Combination Formulation of Tetrodotoxin and Lidocaine as a Potential Therapy for Severe Arrhythmias

by Bihong Hong, Jianlin He, Qingqing Le, Kaikai Bai, Yongqiang Chen and Wenwen Huang

Mar. Drugs 2019, 17(12), 685; https://doi.org/10.3390/md17120685 - 05 Dec 2019

Cited by 18 | Viewed by 3027

Abstract

Severe arrhythmias—such as ventricular arrhythmias—can be fatal, but treatment options are limited. The effects of a combined formulation of tetrodotoxin (TTX) and lidocaine (LID) on severe arrhythmias were studied. Patch clamp recording data showed that the combination of LID and TTX had a [...] Read more.

Severe arrhythmias—such as ventricular arrhythmias—can be fatal, but treatment options are limited. The effects of a combined formulation of tetrodotoxin (TTX) and lidocaine (LID) on severe arrhythmias were studied. Patch clamp recording data showed that the combination of LID and TTX had a stronger inhibitory effect on voltage-gated sodium channel 1.5 (Nav1.5) than that of either TTX or LID alone. LID + TTX formulations were prepared with optimal stability containing 1 μg of TTX, 5 mg of LID, 6 mg of mannitol, and 4 mg of dextran-40 and then freeze dried. This formulation significantly delayed the onset and shortened the duration of arrhythmia induced by aconitine in rats. Arrhythmia-originated death was avoided by the combined formulation, with a decrease in the mortality rate from 64% to 0%. The data also suggests that the anti-arrhythmic effect of the combination was greater than that of either TTX or LID alone. This paper offers new approaches to develop effective medications against arrhythmias. Full article

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11 pages, 1632 KiB

Open AccessArticle

In Vitro Antiproliferative Evaluation of Synthetic Meroterpenes Inspired by Marine Natural Products

by Concetta Imperatore, Gerardo Della Sala, Marcello Casertano, Paolo Luciano, Anna Aiello, Ilaria Laurenzana, Claudia Piccoli and Marialuisa Menna

Mar. Drugs 2019, 17(12), 684; https://doi.org/10.3390/md17120684 - 05 Dec 2019

Cited by 14 | Viewed by 2789

Abstract

Several marine natural linear prenylquinones/hydroquinones have been identified as anticancer and antimutagenic agents. Structure-activity relationship studies on natural compounds and their synthetic analogs demonstrated that these effects depend on the length of the prenyl side chain and on the type and position of [...] Read more.

Several marine natural linear prenylquinones/hydroquinones have been identified as anticancer and antimutagenic agents. Structure-activity relationship studies on natural compounds and their synthetic analogs demonstrated that these effects depend on the length of the prenyl side chain and on the type and position of the substituent groups in the quinone moiety. Aiming to broaden the knowledge of the underlying mechanism of the antiproliferative effect of these prenylated compounds, herein we report the synthesis of two quinones 4 and 5 and of their corresponding dioxothiazine fused quinones 6 and 7 inspired to the marine natural product aplidinone A (1), a geranylquinone featuring the 1,1-dioxo-1,4-thiazine ring isolated from the ascidian Aplidium conicum. The potential effects on viability and proliferation in three different human cancer cell lines, breast adenocarcinoma (MCF-7), pancreas adenocarcinoma (Bx-PC3) and bone osteosarcoma (MG-63), were investigated. The methoxylated geranylquinone 5 exerted the highest antiproliferative effect exhibiting a comparable toxicity in all three cell lines analyzed. Interestingly, a deeper investigation has highlighted a cytostatic effect of quinone 5 referable to a G0/G1 cell-cycle arrest in BxPC-3 cells after 24 h treatment. Full article

(This article belongs to the Special Issue Synthesis of Marine Natural Products and Molecules Inspired by Marine Substances)

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14 pages, 1824 KiB

Open AccessArticle

Bisindole Alkaloids from a New Zealand Deep-Sea Marine Sponge Lamellomorpha strongylata

by Kavita Ragini, Andrew M. Piggott and Peter Karuso

Mar. Drugs 2019, 17(12), 683; https://doi.org/10.3390/md17120683 - 04 Dec 2019

Cited by 12 | Viewed by 2732

Abstract

Chemical investigation of the secondary metabolites of a rare New Zealand deep-sea sponge, Lamellomorpha strongylata, resulted in the isolation of twenty-one indole alkaloids, including two new bisindoles—(Z)-coscinamide D (1), (E)-coscinamide D (2)—and four compounds [...] Read more.

Chemical investigation of the secondary metabolites of a rare New Zealand deep-sea sponge, Lamellomorpha strongylata, resulted in the isolation of twenty-one indole alkaloids, including two new bisindoles—(Z)-coscinamide D (1), (E)-coscinamide D (2)—and four compounds isolated for the first time as natural products—lamellomorphamides A (3), B (4), C (5) and D (6). In addition, fifteen previously reported natural products were isolated, seven of which are seco analogs of hamacanthin alkaloids. The one sponge produces enantiomerically pure but opposite configurations of compounds that only differ in the number of bromines, suggesting enantiodivergent biosynthesis. In addition, four compounds were isolated as partial racemates, suggesting these compounds are biosynthesized via two independent routes. Full article

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13 pages, 3321 KiB

Open AccessReview

Bioactive Nitrogenous Secondary Metabolites from the Marine Sponge Genus Haliclona

by Jiaying Zhu, Yang Liu, Zijun Liu, Hao Wang and Huawei Zhang

Mar. Drugs 2019, 17(12), 682; https://doi.org/10.3390/md17120682 - 03 Dec 2019

Cited by 12 | Viewed by 3357

Abstract

Marine sponge genus Haliclona, one of the most prolific sources of natural products, contains over 600 species but only a small part of them had been classified and chemically investigated. On the basis of extensive literature search, this review firstly summarizes 112 [...] Read more.

Marine sponge genus Haliclona, one of the most prolific sources of natural products, contains over 600 species but only a small part of them had been classified and chemically investigated. On the basis of extensive literature search, this review firstly summarizes 112 nitrogenous secondary metabolites from classified and unclassified Haliclona sponges as well as from their symbiotic microorganisms. Most of these substances have only been found in Haliclona sponges, and display diverse bioactive properties with potential applications in new drug discovery. Full article

(This article belongs to the Special Issue Advances in Marine Alkaloids)

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15 pages, 3174 KiB

Open AccessArticle

Cloning, Expression, and Characterization of a New Glycosaminoglycan Lyase from Microbacterium sp. H14

by Junhao Sun, Xu Han, Guanrui Song, Qianhong Gong and Wengong Yu

Mar. Drugs 2019, 17(12), 681; https://doi.org/10.3390/md17120681 - 02 Dec 2019

Cited by 7 | Viewed by 2338

Abstract

Glycosaminoglycan (GAG) lyase is an effective tool for the structural and functional studies of glycosaminoglycans and preparation of functional oligosaccharides. A new GAG lyase from Microbacterium sp. H14 was cloned, expressed, purified, and characterized, with a molecular weight of approximately 85.9 kDa. The [...] Read more.

Glycosaminoglycan (GAG) lyase is an effective tool for the structural and functional studies of glycosaminoglycans and preparation of functional oligosaccharides. A new GAG lyase from Microbacterium sp. H14 was cloned, expressed, purified, and characterized, with a molecular weight of approximately 85.9 kDa. The deduced lyase HCLaseM belonged to the polysaccharide lyase (PL) family 8. Based on the phylogenetic tree, HCLaseM could not be classified into the existing three subfamilies of this family. HCLaseM showed almost the same enzyme activity towards hyaluronan (HA), chondroitin sulfate A (CS-A), CS-B, CS-C, and CS-D, which was different from reported GAG lyases. HCLaseM exhibited the highest activities to both HA and CS-A at its optimal temperature (35 °C) and pH (pH 7.0). HCLaseM was stable in the range of pH 5.0–8.0 and temperature below 30 °C. The enzyme activity was independent of divalent metal ions and was not obviously affected by most metal ions. HCLaseM is an endo-type enzyme yielding unsaturated disaccharides as the end products. The facilitated diffusion effect of HCLaseM is dose-dependent in animal experiments. These properties make it a candidate for further basic research and application. Full article

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Mar. Drugs, Volume 17, Issue 12 (December 2019) – 62 articles

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