Marine Drugs

19 pages, 3349 KiB

Open AccessArticle

Puffer Fish Gut Microbiota Studies Revealed Unique Bacterial Co-Occurrence Patterns and New Insights on Tetrodotoxin Producers

by Zhenchi Li, Jinglin Tian, Yukun Lai, Chiu-Hong Lee, Zongwei Cai and Chun-Fai Yu

Mar. Drugs 2020, 18(5), 278; https://doi.org/10.3390/md18050278 - 25 May 2020

Cited by 12 | Viewed by 6719

Abstract

Tetrodotoxin (TTX) is a potent neurotoxin isolated mainly from toxic puffer fish. To date, the TTX biosynthetic mechanism inside its hosts remains unresolved. Here, we hypothesize the TTX synthesis relies on the host gut microbiota, including the neglected non-culturable bacteria. In these studies, [...] Read more.

Tetrodotoxin (TTX) is a potent neurotoxin isolated mainly from toxic puffer fish. To date, the TTX biosynthetic mechanism inside its hosts remains unresolved. Here, we hypothesize the TTX synthesis relies on the host gut microbiota, including the neglected non-culturable bacteria. In these studies, we collected the gut contents from 5 puffer fish species of the genus Takifugu including one suspected hybrid species for gut microbiota study by 16S rRNA amplicon metagenomics approach. Their gut samples were divided into toxic and non-toxic groups based on the TTX concentrations in the livers detected by LC-MS/MS. Bacterial diversity studies showed that gut microbiota structures were significantly different between toxic and non-toxic species. Vibrio and Cyanobacteria centered at the gut bacterial co-occurrence network, suggesting their importance in TTX biosynthesis. The results of PICRUSt2 metagenomic prediction and gene set enrichment analysis provided new support of arginine-precursor required in TTX biosynthesis. This is the first study to profile the gut microbiota in toxic and non-toxic puffer fish species by 16S rRNA amplicon metagenomic approach, defining significant microbial co-occurrence patterns in their gut environment. Our data supported the proposed biosynthesis of TTX inside the hosts by their gut bacterial symbionts using arginine as a precursor. Full article

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12 pages, 1544 KiB

Open AccessCommunication

The Influence of Caerulomycin A on the Intestinal Microbiota in SD Rats

by Hongwei Zhang, Mengmeng Lan, Guodong Cui and Weiming Zhu

Mar. Drugs 2020, 18(5), 277; https://doi.org/10.3390/md18050277 - 22 May 2020

Cited by 6 | Viewed by 3193

Abstract

Caerulomycin A (CRM A) is the first example of natural caerulomycins with a 2,2′-bipyridyl ring core and 6-aldoxime functional group from Streptomyces caeruleus and recently from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Our previous study revealed that CRM A showed anti-tumor activity against human colorectal [...] Read more.

Caerulomycin A (CRM A) is the first example of natural caerulomycins with a 2,2′-bipyridyl ring core and 6-aldoxime functional group from Streptomyces caeruleus and recently from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Our previous study revealed that CRM A showed anti-tumor activity against human colorectal cancer (CRC) both in vitro and in vivo. Because some intestinal flora can affect the occurrence and development of CRC, the influence of CRM A on the intestinal flora is worthy of study in Sprague–Dawley (SD) rats. The high throughput sequencing of the V3-V4 hypervariable region in bacterial 16S rDNA gene results showed that the CRM A affected the diversity of intestinal flora of the SD rats treated with CRM A for 2, 3 and 4 weeks. Further analysis indicated that the abundance of genera Prevotella_1, Prevotellaceae_UCG-001, and Lactobacillus were increased while the that of genera Alloprevotella and Ruminiclostridium_1 were decreased. For the CRC related intestinal flora, the abundance of genera Bacteroides, Fusobacterium, Enterococcus, Escherichia-Shigella, Klebsiella, Streptococcus, Ruminococcus_2, and Peptococcus of SD rats treated with CRM A were decreased, while that of abundance of genera Bifidobacterium, Lactobacillus, Faecalibacterium, Blautia, Oscillibacter, and Clostridium were increased. The results indicated that CRM A could influence the intestinal flora by inhibiting some species of harmful flora and improving the beneficial bacteria in intestinal flora in the SD rats. The results may provide a new idea for revealing the mechanism of the anti-CRC activity of CRM A. Full article

(This article belongs to the Special Issue Development and Application of Marine-Sourced Anti-cancer and Cancer Pain Control Agents)

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10 pages, 2363 KiB

Open AccessArticle

Cytotoxic Secondary Metabolites Isolated from the Marine Alga-Associated Fungus Penicillium chrysogenum LD-201810

by Lin-Lin Jiang, Jin-Xiu Tang, Yong-Heng Bo, You-Zhi Li, Tao Feng, Hong-Wei Zhu, Xin Yu, Xing-Xiao Zhang, Jian-Long Zhang and Weiyi Wang

Mar. Drugs 2020, 18(5), 276; https://doi.org/10.3390/md18050276 - 22 May 2020

Cited by 17 | Viewed by 3920

Abstract

A new pentaketide derivative, penilactonol A (1), and two new hydroxyphenylacetic acid derivatives, (2’R)-stachyline B (2) and (2’R)-westerdijkin A (3), together with five known metabolites, bisabolane-type sesquiterpenoids 4–6 and meroterpenoids 7 [...] Read more.

A new pentaketide derivative, penilactonol A (1), and two new hydroxyphenylacetic acid derivatives, (2’R)-stachyline B (2) and (2’R)-westerdijkin A (3), together with five known metabolites, bisabolane-type sesquiterpenoids 4–6 and meroterpenoids 7 and 8, were isolated from the solid culture of a marine alga-associated fungus Penicillium chrysogenum LD-201810. Their structures were elucidated based on extensive spectroscopic analyses, including 1D/2D NMR and high resolution electrospray ionization mass spectra (HRESIMS). The absolute configurations of the stereogenic carbons in 1 were determined by the (Mo₂(OAc)₄)-induced circular dichroism (CD) and comparison of the calculated and experimental electronic circular dichroism (ECD) spectra, while the absolute configuration of the stereogenic carbon in 2 was established using single-crystal X-ray diffraction analysis. Compounds 2 and 3 adapt the 2’R-configuration as compared to known hydroxyphenylacetic acid-derived and O-prenylated natural products. The cytotoxicity of 1–8 against human carcinoma cell lines (A549, BT-549, HeLa, HepG2, MCF-7, and THP-1) was evaluated. Compound 3 exhibited cytotoxicity to the HepG2 cell line with an IC₅₀ value of 22.0 μM. Furthermore, 5 showed considerable activities against A549 and THP-1 cell lines with IC₅₀ values of 21.2 and 18.2 μM, respectively. Full article

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

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17 pages, 1931 KiB

Open AccessArticle

Mechanisms of Bioactivities of Fucoidan from the Brown Seaweed Fucus vesiculosus L. of the Barents Sea

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

Mar. Drugs 2020, 18(5), 275; https://doi.org/10.3390/md18050275 - 22 May 2020

Cited by 126 | Viewed by 8678

Abstract

The aim of this study was to elucidate some mechanisms of radical scavenging and the anti-inflammatory, anti-hyperglycemic, and anti-coagulant bioactivities of high molecular weight fucoidan from Fucus vesiculosus in several in vitro models. Fucoidan has displayed potent 1, 1-diphenyl-2-picryl hydrazil radical scavenging and [...] Read more.

The aim of this study was to elucidate some mechanisms of radical scavenging and the anti-inflammatory, anti-hyperglycemic, and anti-coagulant bioactivities of high molecular weight fucoidan from Fucus vesiculosus in several in vitro models. Fucoidan has displayed potent 1, 1-diphenyl-2-picryl hydrazil radical scavenging and reduction power activities. It significantly inhibits the cyclooxygenase-2 (COX-2) enzyme (IC₅₀ 4.3 μg mL⁻¹) with a greater selectivity index (lg(IC₈₀ COX-2/IC₈₀COX-1), −1.55) than the synthetic non-steroidal anti-inflammatory drug indomethacin (lg(IC₈₀ COX-2/IC₈₀COX-1), −0.09). A concentration-dependent inhibition of hyaluronidase enzyme with an IC₅₀ of 2.9 μg mL⁻¹ was observed. Fucoidan attenuated the lipopolysaccharide-induced expression of mitogen-activated protein kinase p38. Our findings suggest that the inhibition of dipeptidyl peptidase-IV (DPP-IV) (IC₅₀ 1.11 μg mL⁻¹) is one of the possible mechanisms involved in the anti-hyperglycemic activity of fucoidan. At a concentration of 3.2 μg mL⁻¹, fucoidan prolongs the activated partial thromboplastin time and thrombin time by 1.5-fold and 2.5-fold compared with a control, respectively. A significant increase of prothrombin time was observed after the concentration of fucoidan was increased above 80 μg mL⁻¹. This evidenced that fucoidan may have an effect on intrinsic/common pathways and little effect on the extrinsic mechanism. This study sheds light on the multiple pathways of the bioactivities of fucoidan. As far as we know, the inhibition of hyaluronidase and DPP-IV by high molecular fucoidan was studied for the first time in this work. Our results and literature data suggest that molecular weight, sulfate content, fucose content, and polyphenols may contribute to these activities. It seems that high molecular weight fucoidan has promising therapeutic applications in different pharmacological settings. Anti-oxidant, anti-inflammatory and anti-coagulant drugs have been used for the management of complications of COVID19. Taken as a whole, fucoidan could be considered as a prospective candidate for the treatment of patients with COVID19; however, additional research in this field is required. Full article

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27 pages, 4360 KiB

Open AccessReview

Northern Sea Cucumber (Cucumaria frondosa): A Potential Candidate for Functional Food, Nutraceutical, and Pharmaceutical Sector

by Abul Hossain, Deepika Dave and Fereidoon Shahidi

Mar. Drugs 2020, 18(5), 274; https://doi.org/10.3390/md18050274 - 22 May 2020

Cited by 99 | Viewed by 14401

Abstract

Sea cucumber (Cucumaria frondosa) is the most abundant and widely distributed species in the cold waters of North Atlantic Ocean. C. frondosa contains a wide range of bioactive compounds, mainly collagen, cerebrosides, glycosaminoglycan, chondroitin sulfate, saponins, phenols, and mucopolysaccharides, which demonstrate [...] Read more.

Sea cucumber (Cucumaria frondosa) is the most abundant and widely distributed species in the cold waters of North Atlantic Ocean. C. frondosa contains a wide range of bioactive compounds, mainly collagen, cerebrosides, glycosaminoglycan, chondroitin sulfate, saponins, phenols, and mucopolysaccharides, which demonstrate unique biological and pharmacological properties. In particular, the body wall of this marine invertebrate is the major edible part and contains most of the active constituents, mainly polysaccharides and collagen, which exhibit numerous biological activities, including anticancer, anti-hypertensive, anti-angiogenic, anti-inflammatory, antidiabetic, anti-coagulation, antimicrobial, antioxidation, and anti- osteoclastogenic properties. In particular, triterpene glycosides (frondoside A and other) are the most researched group of compounds due to their potential anticancer activity. This review summarizes the latest information on C. frondosa, mainly geographical distribution, landings specific to Canadian coastlines, processing, commercial products, trade market, bioactive compounds, and potential health benefits in the context of functional foods and nutraceuticals. Full article

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20 pages, 2891 KiB

Open AccessArticle

Chitosan Oligosaccharide Fluorinated Derivative Control Root-Knot Nematode (Meloidogyne incognita) Disease Based on the Multi-Efficacy Strategy

by Zhaoqian Fan, Yukun Qin, Song Liu, Ronge Xing, Huahua Yu and Pengcheng Li

Mar. Drugs 2020, 18(5), 273; https://doi.org/10.3390/md18050273 - 22 May 2020

Cited by 30 | Viewed by 4098

Abstract

Plant root-knot nematode disease is a great agricultural problem and commercially available nematicides have the disadvantages of high toxicity and limited usage; thus, it is urgent to develop new nematicides derived from nature substances. In this study, a novel fluorinated derivative was synthesized [...] Read more.

Plant root-knot nematode disease is a great agricultural problem and commercially available nematicides have the disadvantages of high toxicity and limited usage; thus, it is urgent to develop new nematicides derived from nature substances. In this study, a novel fluorinated derivative was synthesized by modifying chitosan oligosaccharide (COS) using the strategy of multiple functions. The derivatives were characterized by FTIR, NMR, elemental analysis, and TG/DTG. The activity assays show that the derivatives can effectively kill the second instar larvae of Meloidogyne incognita in vitro, among them, chitosan-thiadiazole-trifluorobutene (COSSZFB) perform high eggs hatching inhibitory activity. The derivatives can regulate plant growth (photosynthetic pigment), improve immunity (chitinase and β-1,3-glucanase), and show low cytotoxicity and phytotoxicity. According to the multi-functional activity, the derivatives exhibit a good control effect on plant root-knot nematode disease in vivo. The results demonstrate that the COS derivatives (especially fluorinated derivative) perform multiple activities and show the potential to be further evaluated as nematicides. Full article

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17 pages, 1993 KiB

Open AccessArticle

Quorum Sensing Inhibitory and Antifouling Activities of New Bromotyrosine Metabolites from the Polynesian Sponge Pseudoceratina n. sp.

by Florent Tintillier, Céline Moriou, Sylvain Petek, Marilyne Fauchon, Claire Hellio, Denis Saulnier, Merrick Ekins, John N. A. Hooper, Ali Al-Mourabit and Cécile Debitus

Mar. Drugs 2020, 18(5), 272; https://doi.org/10.3390/md18050272 - 21 May 2020

Cited by 26 | Viewed by 4145

Abstract

Four new brominated tyrosine metabolites, aplyzanzines C–F (1–4), were isolated from the French Polynesian sponge Pseudoceratina n. sp., along with the two known 2-aminoimidazolic derivatives, purealidin A (5) and 6, previously isolated, respectively, from the sponges [...] Read more.

Four new brominated tyrosine metabolites, aplyzanzines C–F (1–4), were isolated from the French Polynesian sponge Pseudoceratina n. sp., along with the two known 2-aminoimidazolic derivatives, purealidin A (5) and 6, previously isolated, respectively, from the sponges Psammaplysilla purpurea and Verongula sp. Their structures were assigned based on the interpretation of their NMR and HRMS data. The compounds exhibited quorum sensing inhibition (QSi) and antifouling activities against several strains of bacteria and microalgae. To our knowledge, the QSi activity of this type of bromotyrosine metabolite is described here for the first time. Full article

(This article belongs to the Special Issue Marine Natural Product of the South Pacific Area)

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10 pages, 2160 KiB

Open AccessArticle

¹H NMR-Based Isolation of Anti-Inflammatory 9,11-Secosteroids from the Octocoral Sinularia leptoclados

by Yu-Chia Chang, Kuei-Hung Lai, Sunil Kumar, Po-Jen Chen, Yi-Hsuan Wu, Ching-Long Lai, Hsi-Lung Hsieh, Ping-Jyun Sung and Tsong-Long Hwang

Mar. Drugs 2020, 18(5), 271; https://doi.org/10.3390/md18050271 - 21 May 2020

Cited by 13 | Viewed by 2994

Abstract

Octocoral Sinularia leptoclados has been identified as a source of bioactive 9,11-secosteroids. This study adopted a targeted isolation approach to the discovery and analysis of five 9,11-secosteroids, including two novel compounds named sinleptosterols A (1) and B (2) as [...] Read more.

Octocoral Sinularia leptoclados has been identified as a source of bioactive 9,11-secosteroids. This study adopted a targeted isolation approach to the discovery and analysis of five 9,11-secosteroids, including two novel compounds named sinleptosterols A (1) and B (2) as well as five known analogues (8αH-3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9-one (3), 8βH-3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9-one (4), leptosterol A (5), (24S)-3β,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9-one (6), and 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (7)) in terms of ¹H-NMR patterns and potency against neutrophilic inflammation. The structure of secosteroids 1 and 2 was deduced from general spectroscopic analysis and an examination of NMR spectra. Among the above-mentioned isolates, compound 4 had the most pronounced effect in inhibiting elastase release and superoxide anion generation, with the IC₅₀ values of 2.96 and 1.63 μM, respectively. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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21 pages, 5285 KiB

Open AccessArticle

Bactericidal Activity of Usnic Acid-Chitosan Nanoparticles against Persister Cells of Biofilm-Forming Pathogenic Bacteria

by Fazlurrahman Khan, Hongsik Yu and Young-Mog Kim

Mar. Drugs 2020, 18(5), 270; https://doi.org/10.3390/md18050270 - 20 May 2020

Cited by 29 | Viewed by 4127

Abstract

The present study aimed to prepare usnic acid (UA)-loaded chitosan (CS) nanoparticles (UA-CS NPs) and evaluate its antibacterial activity against biofilm-forming pathogenic bacteria. UA-CS NPs were prepared through simple ionic gelification of UA with CS, and further characterized using Fourier transform infrared spectroscopy, [...] Read more.

The present study aimed to prepare usnic acid (UA)-loaded chitosan (CS) nanoparticles (UA-CS NPs) and evaluate its antibacterial activity against biofilm-forming pathogenic bacteria. UA-CS NPs were prepared through simple ionic gelification of UA with CS, and further characterized using Fourier transform infrared spectroscopy, X-ray diffraction, and field-emission transmission electron microscopy. The UA-CS NPs presented a loading capacity (LC) of 5.2%, encapsulation efficiency (EE) of 24%, and a spherical shape and rough surface. The maximum release of UA was higher in pH 1.2 buffer solution as compared to that in pH 6.8 and 7.4 buffer solution. The average size and zeta potential of the UA-CS NPs was 311.5 ± 49.9 nm in diameter and +27.3 ± 0.8 mV, respectively. The newly prepared UA-CS NPs exhibited antibacterial activity against persister cells obtained from the stationary phase in batch culture, mature biofilms, and antibiotic-induced gram-positive and gram-negative pathogenic bacteria. Exposure of sub-inhibitory concentrations of UA-CS NPs to the bacterial cells resulted in a change in morphology. The present study suggests an alternative method for the application of UA into nanoparticles. Furthermore, the anti-persister activity of UA-CS NPs may be another possible strategy for the treatment of infections caused by biofilm-forming pathogenic bacteria. Full article

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18 pages, 1996 KiB

Open AccessArticle

Characterization of a New Mixture of Mono-Rhamnolipids Produced by Pseudomonas gessardii Isolated from Edmonson Point (Antarctica)

by Carmine Buonocore, Pietro Tedesco, Giovanni Andrea Vitale, Fortunato Palma Esposito, Rosa Giugliano, Maria Chiara Monti, Maria Valeria D’Auria and Donatella de Pascale

Mar. Drugs 2020, 18(5), 269; https://doi.org/10.3390/md18050269 - 20 May 2020

Cited by 24 | Viewed by 4825

Abstract

Rhamnolipids (RLs) are surface-active molecules mainly produced by Pseudomonas spp. Antarctica is one of the less explored places on Earth and bioprospecting for novel RL producer strains represents a promising strategy for the discovery of novel structures. In the present study, 34 cultivable [...] Read more.

Rhamnolipids (RLs) are surface-active molecules mainly produced by Pseudomonas spp. Antarctica is one of the less explored places on Earth and bioprospecting for novel RL producer strains represents a promising strategy for the discovery of novel structures. In the present study, 34 cultivable bacteria isolated from Edmonson Point Lake, Ross Sea, Antarctica were subjected to preliminary screening for the biosurfactant activity. The positive strains were identified by 16S rRNA gene sequencing and the produced RLs were characterized by liquid chromatography coupled to high resolution mass spectrometry (LC-HRESIMS) and liquid chromatography coupled with tandem spectrometry (LC-MS/MS), resulting in a new mixture of 17 different RL congeners, with six previously undescribed RLs. We explored the influence of the carbon source on the RL composition using 12 different raw materials, such as monosaccharides, polysaccharides and petroleum industry derivatives, reporting for the first time the production of RLs using, as sole carbon source, anthracene and benzene. Moreover, we investigated the antimicrobial potential of the RL mixture, towards a panel of both Gram-positive and Gram-negative pathogens, reporting very interesting results towards Listeria monocytogenes with a minimum inhibitory concentration (MIC) value of 3.13 µg/mL. Finally, we report for the first time the antimicrobial activity of RLs towards three strains of the emerging multidrug resistant Stenotrophomonas maltophilia with MIC values of 12.5 µg/mL. Full article

(This article belongs to the Special Issue Papers from MarPipe and Ocean Medicines)

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17 pages, 4539 KiB

Open AccessArticle

Structure and In Vitro Bioactivity against Cancer Cells of the Capsular Polysaccharide from the Marine Bacterium Psychrobacter marincola

by Maxim S. Kokoulin, Alexandra S. Kuzmich, Lyudmila A. Romanenko, Irina V. Chikalovets and Oleg V. Chernikov

Mar. Drugs 2020, 18(5), 268; https://doi.org/10.3390/md18050268 - 19 May 2020

Cited by 11 | Viewed by 3425

Abstract

Psychrobacter marincola KMM 277^T is a psychrophilic Gram-negative bacterium that has been isolated from the internal tissues of an ascidian Polysyncraton sp. Here, we report the structure of the capsular polysaccharide from P. marincola KMM 277^T and its effect on the [...] Read more.

Psychrobacter marincola KMM 277^T is a psychrophilic Gram-negative bacterium that has been isolated from the internal tissues of an ascidian Polysyncraton sp. Here, we report the structure of the capsular polysaccharide from P. marincola KMM 277^T and its effect on the viability and colony formation of human acute promyelocytic leukemia HL-60 cells. The polymer was purified by several separation methods, including ultracentrifugation and chromatographic procedures, and the structure was elucidated by means of chemical analysis, 1-D, and 2-D NMR spectroscopy techniques. It was found that the polysaccharide consists of branched hexasaccharide repeating units containing two 2-N-acetyl-2-deoxy-d-galacturonic acids, and one of each of 2-N-acetyl-2-deoxy-d-glucose, d-glucose, d-ribose, and 7-N-acetylamino-3,5,7,9-tetradeoxy-5-N-[(R)-2-hydroxypropanoylamino]- l-glycero-l-manno-non-2-ulosonic acid. To our knowledge, this is the first finding a pseudaminic acid decorated with lactic acid residue in polysaccharides. The biological analysis showed that the capsular polysaccharide significantly reduced the viability and colony formation of HL-60 cells. Taken together, our data indicate that the capsular polysaccharide from P. marincola KMM 277^T is a promising substance for the study of its antitumor properties and the mechanism of action in the future. Full article

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

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13 pages, 2455 KiB

Open AccessArticle

CYC31, A Natural Bromophenol PTP1B Inhibitor, Activates Insulin Signaling and Improves Long Chain-Fatty Acid Oxidation in C2C12 Myotubes

by Jiao Luo, Yufei Hou, Mengyue Xie, Wanli Ma, Dayong Shi and Bo Jiang

Mar. Drugs 2020, 18(5), 267; https://doi.org/10.3390/md18050267 - 19 May 2020

Cited by 14 | Viewed by 4323

Abstract

3-bromo-4,5-Bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (CYC31) is a bromophenol protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from the red alga Rhodomela confervoides. Here, the effect of CYC31 on the insulin signaling and fatty-acid-induced disorders in C2C12 myotubes was investigated. Molecular docking assay showed that CYC31 was [...] Read more.

3-bromo-4,5-Bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (CYC31) is a bromophenol protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from the red alga Rhodomela confervoides. Here, the effect of CYC31 on the insulin signaling and fatty-acid-induced disorders in C2C12 myotubes was investigated. Molecular docking assay showed that CYC31 was embedded into the catalytic pocket of PTP1B. A cellular study found that CYC31 increased the activity of insulin signaling and promoted 2-NBDG uptake through GLUT4 translocation in C2C12 myotubes. Further studies showed that CYC31 ameliorated palmitate-induced insulin resistance in C2C12 myotubes. Moreover, CYC31 treatment significantly increased the mRNA expression of carnitine palmitoyltransferase 1B (CPT-1B) and fatty acid binding protein 3 (FABP3), which was tightly linked with fatty acid oxidation. These findings suggested that CYC31 could prevent palmitate-induce insulin resistance and could improve fatty acid oxidation through PTP1B inhibition. Full article

(This article belongs to the Special Issue Therapeutic Marine Enzyme Inhibitors as Leads for the Discovery of New Bioactive Drugs)

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14 pages, 2579 KiB

Open AccessArticle

Astaxanthin Modulates Apoptotic Molecules to Induce Death of SKBR3 Breast Cancer Cells

by Min Sung Kim, Yong Tae Ahn, Chul Won Lee, Hyungwoo Kim and Won Gun An

Mar. Drugs 2020, 18(5), 266; https://doi.org/10.3390/md18050266 - 19 May 2020

Cited by 22 | Viewed by 4811

Abstract

Astaxanthin (AST) is related to apoptosis but the details of the mechanism of how AST makes apoptosis is not clear. The present study investigated apoptotic effects of AST to SKBR3, a breast cancer cell line in detail. Cell viability assay showed cellular proliferation [...] Read more.

Astaxanthin (AST) is related to apoptosis but the details of the mechanism of how AST makes apoptosis is not clear. The present study investigated apoptotic effects of AST to SKBR3, a breast cancer cell line in detail. Cell viability assay showed cellular proliferation and morphological changes of the cells were observed under AST treatment. FACS analysis indicated that AST blocked cell cycle progression at G0/G1, suppressed proliferation dose-dependently, and induced apoptosis of the cells. The apoptosis of the cells by AST was further demonstrated through the decreased expression level of mutp53 and cleaved a PARP-1 fragment, respectively. In addition, AST induced the intrinsic apoptosis of the cells by activation of Bax/Bcl2, cleaved caspase-3, and cleaved caspase-9 as well as the phosphorylation of ERK1/2, JNK, and p38. Furthermore, AST decreased production of intracellular reactive oxygen species as well as modulated expressions of superoxide dismutases and Pontin, an anti-apoptotic factor. Co-immunoprecipitation assay revealed AST reduced interaction between Pontin and mutant p53. Taken together, these studies proved that AST regulates the expression of apoptotic molecules to induce intrinsic apoptosis of the cells, suggesting AST therapy might provide an alternative for improving the efficacies of other anti-cancer therapies for breast cancer. Full article

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20 pages, 2261 KiB

Open AccessReview

Fish-Based Bioactives as Potent Nutraceuticals: Exploring the Therapeutic Perspective of Sustainable Food from the Sea

by Syed Amir Ashraf, Mohd Adnan, Mitesh Patel, Arif Jamal Siddiqui, Manojkumar Sachidanandan, Mejdi Snoussi and Sibte Hadi

Mar. Drugs 2020, 18(5), 265; https://doi.org/10.3390/md18050265 - 18 May 2020

Cited by 69 | Viewed by 8476

Abstract

Recent developments in nutraceuticals and functional foods have confirmed that bioactive components present in our diet play a major therapeutic role against human diseases. Moreover, there is a huge emphasis on food scientists for identifying and producing foods with better bioactive activity, which [...] Read more.

Recent developments in nutraceuticals and functional foods have confirmed that bioactive components present in our diet play a major therapeutic role against human diseases. Moreover, there is a huge emphasis on food scientists for identifying and producing foods with better bioactive activity, which can ultimately provide wellness and well-being to human health. Among the several well-known foods with bioactive constituents, fish has always been considered important, due to its rich nutritional values and by-product application in food industries. Nutritionists, food scientists, and other scientific communities have been working jointly to uncover new bioactive molecules that could increase the potential and therapeutic benefits of these bioactive components. Despite the innumerable benefits of fish and known fish bioactive molecules, its use by food or pharmaceutical industries is scarce, and even research on fish-based nutraceuticals is not promising. Therefore, this review focuses on the current information/data available regarding fish bioactive components, its application as nutraceuticals for therapeutic purposes in the treatment of chronic diseases, ethnic issues related to consumption of fish or its by-products. Especial emphasis is given on the utilization of fish wastes and its by-products to fulfill the world demand for cheap dietary supplements specifically for underdeveloped/least developed countries. Full article

(This article belongs to the Special Issue Nutraceuticals and Pharmaceuticals from Marine Fish and Invertebrates)

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31 pages, 11898 KiB

Open AccessFeature PaperReview

Analysis of Scientific Research Driving Microalgae Market Opportunities in Europe

by Judith Rumin, Elodie Nicolau, Raimundo Gonçalves de Oliveira Junior, Claudio Fuentes-Grünewald and Laurent Picot

Mar. Drugs 2020, 18(5), 264; https://doi.org/10.3390/md18050264 - 18 May 2020

Cited by 67 | Viewed by 8086

Abstract

A bibliographic database of scientific papers published by authors affiliated to research institutions worldwide, especially focused in Europe and in the European Atlantic Area, and containing the keywords “microalga(e)” or “phytoplankton” was built. A corpus of 79,020 publications was obtained and analyzed using [...] Read more.

A bibliographic database of scientific papers published by authors affiliated to research institutions worldwide, especially focused in Europe and in the European Atlantic Area, and containing the keywords “microalga(e)” or “phytoplankton” was built. A corpus of 79,020 publications was obtained and analyzed using the Orbit Intellixir software to characterize the research trends related to microalgae markets, markets opportunities and technologies that could have important impacts on markets evolution. Six major markets opportunities, the production of biofuels, bioplastics, biofertilizers, nutraceuticals, pharmaceuticals and cosmetics, and two fast-evolving technological domains driving markets evolution, microalgae harvesting and extraction technologies and production of genetically modified (GM-)microalgae, were highlighted. We here present an advanced analysis of these research domains to give an updated overview of scientific concepts driving microalgae markets. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae 2.0)

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14 pages, 1509 KiB

Open AccessArticle

Effect of Chitosan as a Cross-Linker on Matrix Metalloproteinase Activity and Bond Stability with Different Adhesive Systems

by Eugenia Baena, Sandra R Cunha, Tatjana Maravić, Allegra Comba, Federica Paganelli, Giulio Alessandri-Bonetti, Laura Ceballos, Franklin R Tay, Lorenzo Breschi and Annalisa Mazzoni

Mar. Drugs 2020, 18(5), 263; https://doi.org/10.3390/md18050263 - 18 May 2020

Cited by 29 | Viewed by 3719

Abstract

The aim of the present study was to evaluate the effect of 0.1% chitosan (Ch) solution as an additional primer on the mechanical durability and enzymatic activity on dentine using an etch-and-rinse (E&R) adhesive and a universal self-etch (SE) adhesive. Microtensile bond strength [...] Read more.

The aim of the present study was to evaluate the effect of 0.1% chitosan (Ch) solution as an additional primer on the mechanical durability and enzymatic activity on dentine using an etch-and-rinse (E&R) adhesive and a universal self-etch (SE) adhesive. Microtensile bond strength and interfacial nanoleakage expression of the bonded interfaces for all adhesives (with or without pretreatment with 0.1% Ch solution for 1 min and air-dried for 5 s) were analyzed immediately and after 10,000 thermocycles. Zymograms of protein extracts from human dentine powder incubated with Optibond FL and Scotchbond Universal on untreated or Ch-treated dentine were obtained to examine dentine matrix metalloproteinase (MMP) activities. The use of 0.1% Ch solution as an additional primer in conjunction with the E&R or SE adhesive did not appear to have influenced the immediate bond strength (T0) or bond strength after thermocycling (T1). Zymography showed a reduction in MMP activities only for mineralized and demineralized dentine powder after the application of Ch. Application of 0.1% Ch solution does not increase the longevity of resin–dentine bonds. Nonetheless, the procedure appears to be proficient in reducing dentine MMP activities within groups without adhesive treatments. Further studies are required to comprehend the cross-linking of Ch with dentine collagen. Full article

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23 pages, 770 KiB

Open AccessArticle

The Effects of the Marine-Derived Polysaccharides Laminarin and Chitosan on Aspects of Colonic Health in Pigs Challenged with Dextran Sodium Sulphate

by Ruth Rattigan, John V. O’Doherty, Stafford Vigors, Marion T. Ryan, Rocco S. Sebastiano, John J. Callanan, Kevin Thornton, Gaurav Rajauria, Lekha M. Margassery, Alan D. W. Dobson, Niall D. O’Leary and Torres Sweeney

Mar. Drugs 2020, 18(5), 262; https://doi.org/10.3390/md18050262 - 16 May 2020

Cited by 16 | Viewed by 4670

Abstract

This study examined the effects of dietary supplementation with laminarin or chitosan on colonic health in pigs challenged with dextran sodium sulphate (DSS). Weaned pigs were assigned to: (1) a basal diet (n = 22); (2) a basal diet + laminarin (n = [...] Read more.

This study examined the effects of dietary supplementation with laminarin or chitosan on colonic health in pigs challenged with dextran sodium sulphate (DSS). Weaned pigs were assigned to: (1) a basal diet (n = 22); (2) a basal diet + laminarin (n = 10); and (3) a basal diet + chitosan (n = 10). On d35, the basal group was split, creating four groups: (1) the basal diet (control); (2) the basal diet + DSS; (3) the basal diet + laminarin + DSS; and (4) the basal diet + chitosan + DSS. From d39–42, the pigs were orally challenged with DSS. On d44, colonic tissue/digesta samples were collected. The basal DSS group had reduced growth, higher pathology score and an increased expression of MMP1, IL13 and IL23 compared with the controls (p < 0.05); these parameters were similar between the DSS-challenged groups (p > 0.05). In the basal DSS group, the relative abundance of beneficial taxa including Prevotella and Roseburia were reduced while Escherichia/Shigella were increased, compared with the controls (p < 0.05). The relative abundance of Escherichia/Shigella was reduced and the molar proportions of acetate were increased in the laminarin DSS group compared with the basal DSS group (p < 0.01), suggesting that laminarin has potential to prevent pathogen proliferation and enhance the volatile fatty acid profile in the colon in a porcine model of colitis. Full article

(This article belongs to the Special Issue Marine-Derived Compounds Applied in Intestinal Diseases)

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19 pages, 4166 KiB

Open AccessArticle

Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

by Hyocheol Bae, Jin-Young Lee, Gwonhwa Song and Whasun Lim

Mar. Drugs 2020, 18(5), 261; https://doi.org/10.3390/md18050261 - 16 May 2020

Cited by 28 | Viewed by 3618

Abstract

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared [...] Read more.

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer. Full article

(This article belongs to the Special Issue Antiproliferative Marine Natural Products Inducing Non-apoptotic Cell Death or Chemosentisizing Cancer Cells)

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14 pages, 2209 KiB

Open AccessArticle

New Conjugates of Polyhydroxysteroids with Long-Chain Fatty Acids from the Deep-Water Far Eastern Starfish Ceramaster patagonicus and Their Anticancer Activity

by Timofey V. Malyarenko, Alla A. Kicha, Olesya S. Malyarenko, Viktor M. Zakharenko, Ivan P. Kotlyarov, Anatoly I. Kalinovsky, Roman S. Popov, Vasily I. Svetashev and Natalia V. Ivanchina

Mar. Drugs 2020, 18(5), 260; https://doi.org/10.3390/md18050260 - 15 May 2020

Cited by 3 | Viewed by 4626

Abstract

Four new conjugates, esters of polyhydroxysteroids with long-chain fatty acids (1–4), were isolated from the deep-water Far Eastern starfish Ceramaster patagonicus. The structures of 1–4 were established by NMR and ESIMS techniques as well as chemical transformations. [...] Read more.

Four new conjugates, esters of polyhydroxysteroids with long-chain fatty acids (1–4), were isolated from the deep-water Far Eastern starfish Ceramaster patagonicus. The structures of 1–4 were established by NMR and ESIMS techniques as well as chemical transformations. Unusual compounds 1–4 contain the same 5α-cholestane-3β,6β,15α,16β,26-pentahydroxysteroidal moiety and differ from each other in the fatty acid units: 5′Z,11′Z-octadecadienoic (1), 11′Z-octadecenoic (2), 5′Z,11′Z-eicosadienoic (3), and 7′Z-eicosenoic (4) acids. Previously, only one such steroid conjugate with a fatty acid was known from starfish. After 72 h of cell incubation, using MTS assay it was found that the concentrations of compounds 1, 2, and 3 that caused 50% inhibition of growth (IC₅₀) of JB6 Cl41 cells were 81, 40, and 79 µM, respectively; for MDA-MB-231 cells, IC₅₀ of compounds 1, 2, and 3 were 74, 33, and 73 µM, respectively; for HCT 116 cells, IC₅₀ of compounds 1, 2, and 3 were 73, 31, and 71 µM, respectively. Compound 4 was non-toxic against tested cell lines even in three days of treatment. Compound 2 (20 µM) suppressed colony formation and migration of MDA-MB-231 and HCT 116 cells. Full article

(This article belongs to the Special Issue Echinoderms Metabolites: Structure, Functions and Biomedical Perspectives)

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18 pages, 1298 KiB

Open AccessArticle

The Biotechnological Potential of the Marine Diatom Skeletonema dohrnii to the Elevated Temperature and pCO₂

by Satheeswaran Thangaraj and Jun Sun

Mar. Drugs 2020, 18(5), 259; https://doi.org/10.3390/md18050259 - 15 May 2020

Cited by 15 | Viewed by 3562

Abstract

Marine diatoms are promising candidates for biotechnological applications, since they contain high-value compounds, naturally. To facilitate the production of these compounds, stress conditions are often preferable; however, challenges remain with respect to maximizing a metabolic potential for the large-scale cultivation. Here, we sequenced [...] Read more.

Marine diatoms are promising candidates for biotechnological applications, since they contain high-value compounds, naturally. To facilitate the production of these compounds, stress conditions are often preferable; however, challenges remain with respect to maximizing a metabolic potential for the large-scale cultivation. Here, we sequenced the transcriptome of diatom Skeletonema dohrnii under the actual (21 °C, 400 ppm) and elevated (25 °C, 1000 ppm) temperature and pCO₂ condition. Results indicated that cells grown at higher temperature and pCO₂ showed increasing growth rate, pigment composition, and biochemical productivity as did the expression of chlorophyll, carotenoid and bioactive compound related genes or transcripts. Furthermore, performing de novo transcriptome, we identified 32,884 transcript clusters and found 10,974 of them were differentially expressed between these two conditions. Analyzing the functions of differentially expressed transcripts, we found many of them involved in core metabolic and biosynthesis pathways, including chlorophyll metabolism, carotenoid, phenylpropanoid, phenylalanine and tyrosine, and flavonoid biosynthesis was upregulated. Moreover, we here demonstrated that utilizing a unique bio-fixation ability, S. dohrnii is capable of suppressing central carbon metabolism to promote lipid productivity, fatty acid contents and other bioactive compounds under high temperature and pCO₂ treatment. Our study suggests that this S. dohrnii species could be a potential candidate for wide-scale biotechnological applications under elevated temperature and CO₂ conditions. Full article

(This article belongs to the Special Issue Biotechnological Applications of Marine Photosynthetic Organisms)

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11 pages, 1577 KiB

Open AccessArticle

Bioactive Metabolites from the Mariana Trench Sediment-Derived Fungus Penicillium sp. SY2107

by Sidra Kaleem, Le Qin, Wenwen Yi, Xiao-Yuan Lian and Zhizhen Zhang

Mar. Drugs 2020, 18(5), 258; https://doi.org/10.3390/md18050258 - 14 May 2020

Cited by 25 | Viewed by 3460

Abstract

Mariana Trench sediments are enriched in microorganisms, however, the structures and bioactivities of their secondary metabolites are not very known. In this study, a fungus Penicillium sp. SY2107 was isolated from a sample of Mariana Trench sediment collected at a depth of 11000 [...] Read more.

Mariana Trench sediments are enriched in microorganisms, however, the structures and bioactivities of their secondary metabolites are not very known. In this study, a fungus Penicillium sp. SY2107 was isolated from a sample of Mariana Trench sediment collected at a depth of 11000 m and an extract prepared from the culture of this fungus in rice medium showed antimicrobial activities. Chemical investigation on this active extract led to the isolation of 16 compounds, including one novel meroterpenoid, named andrastone C. Structure of the new compound was elucidated based on high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, extensive nuclear magnetic resonance (NMR) spectroscopic analyses and a single crystal X-ray diffraction. The crystal structure of a known meroterpenoid andrastone B was also reported in this study. Both andrastones B and C exhibited antimicrobial activities against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans with minimum inhibitory concentration (MIC) values in a range from 6 to 13 μg/mL. Full article

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12 pages, 686 KiB

Open AccessReview

Pheophorbide a: State of the Art

by Assunta Saide, Chiara Lauritano and Adrianna Ianora

Mar. Drugs 2020, 18(5), 257; https://doi.org/10.3390/md18050257 - 14 May 2020

Cited by 75 | Viewed by 7954

Abstract

Chlorophyll breakdown products are usually studied for their antioxidant and anti-inflammatory activities. The chlorophyll derivative Pheophorbide a (PPBa) is a photosensitizer that can induce significant anti-proliferative effects in several human cancer cell lines. Cancer is a leading cause of death worldwide, [...] Read more.

Chlorophyll breakdown products are usually studied for their antioxidant and anti-inflammatory activities. The chlorophyll derivative Pheophorbide a (PPBa) is a photosensitizer that can induce significant anti-proliferative effects in several human cancer cell lines. Cancer is a leading cause of death worldwide, accounting for about 9.6 million deaths, in 2018 alone. Hence, it is crucial to monitor emergent compounds that show significant anticancer activity and advance them into clinical trials. In this review, we analyze the anticancer activity of PPBa with or without photodynamic therapy and also conjugated with or without other chemotherapic drugs, highlighting the capacity of PPBa to overcome multidrug resistance. We also report other activities of PPBa and different pathways that it can activate, showing its possible applications for the treatment of human pathologies. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae 2.0)

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26 pages, 2835 KiB

Open AccessArticle

Graph-Directed Approach for Downselecting Toxins for Experimental Structure Determination

by Rachael A. Mansbach, Srirupa Chakraborty, Timothy Travers and S. Gnanakaran

Mar. Drugs 2020, 18(5), 256; https://doi.org/10.3390/md18050256 - 14 May 2020

Cited by 4 | Viewed by 3058

Abstract

Conotoxins are short, cysteine-rich peptides of great interest as novel therapeutic leads and of great concern as lethal biological agents due to their high affinity and specificity for various receptors involved in neuromuscular transmission. Currently, of the approximately 6000 known conotoxin sequences, only [...] Read more.

Conotoxins are short, cysteine-rich peptides of great interest as novel therapeutic leads and of great concern as lethal biological agents due to their high affinity and specificity for various receptors involved in neuromuscular transmission. Currently, of the approximately 6000 known conotoxin sequences, only about 3% have associated structural characterization, which leads to a bottleneck in rapid high-throughput screening (HTS) for identification of potential leads or threats. In this work, we combine a graph-based approach with homology modeling to expand the library of conotoxin structures and to identify those conotoxin sequences that are of the greatest value for experimental structural characterization. The latter would allow for the rapid expansion of the known structural space for generating high quality template-based models. Our approach generalizes to other evolutionarily-related, short, cysteine-rich venoms of interest. Overall, we present and validate an approach for venom structure modeling and experimental guidance and employ it to produce a 290%-larger library of approximate conotoxin structures for HTS. We also provide a set of ranked conotoxin sequences for experimental structure determination to further expand this library. Full article

(This article belongs to the Special Issue Virtual Screening of Marine Natural Products)

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11 pages, 1924 KiB

Open AccessArticle

Bioactive Molecules from Mangrove Streptomyces qinglanensis 172205

by Dongbo Xu, Erli Tian, Fandong Kong and Kui Hong

Mar. Drugs 2020, 18(5), 255; https://doi.org/10.3390/md18050255 - 13 May 2020

Cited by 9 | Viewed by 3196

Abstract

Five new compounds 15R-17,18-dehydroxantholipin (1), (3E,5E,7E)-3-methyldeca-3,5,7-triene-2,9-dione (2) and qinlactone A–C (3–5) were identified from mangrove Streptomyces qinglanensis 172205 with “genetic dereplication,” which deleted the highly expressed secondary [...] Read more.

Five new compounds 15R-17,18-dehydroxantholipin (1), (3E,5E,7E)-3-methyldeca-3,5,7-triene-2,9-dione (2) and qinlactone A–C (3–5) were identified from mangrove Streptomyces qinglanensis 172205 with “genetic dereplication,” which deleted the highly expressed secondary metabolite-enterocin biosynthetic gene cluster. The chemical structures were established by spectroscopic methods, and the absolute configurations were determined by electronic circular dichroism (ECD). Compound 1 exhibited strong anti-microbial and antiproliferative bioactivities, while compounds 2–4 showed weak antiproliferative activities. Full article

(This article belongs to the Special Issue Bioactive Molecules from Marine Microorganisms)

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13 pages, 2325 KiB

Open AccessArticle

Anti-Influenza A Virus Activity of Rhamnan Sulfate from Green Algae Monostroma nitidum in Mice with Normal and Compromised Immunity

by Masahiro Terasawa, Kyoko Hayashi, Jung-Bum Lee, Kaoru Nishiura, Koichi Matsuda, Toshimitsu Hayashi and Toshio Kawahara

Mar. Drugs 2020, 18(5), 254; https://doi.org/10.3390/md18050254 - 13 May 2020

Cited by 28 | Viewed by 5420

Abstract

Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga Monostroma nitidum. Here, we aimed [...] Read more.

Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga Monostroma nitidum. Here, we aimed to demonstrate the antiviral activity of RS, especially against influenza A virus (IFV) infection, in vitro and in vivo. RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro. Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption and entry steps. The oral administration of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types. The oral administration of RS also had stimulatory effects on neutralizing antibody production. Fluorescent analysis showed that RS colocalized with M cells in Peyer’s patches, suggesting that RS bound to the M cells and may be incorporated into the Peyer’s patches, which are essential to intestinal immunity. In summary, RS inhibits influenza virus infection and promotes antibody production, suggesting that RS is a potential candidate for the treatment of influenza virus infections. Full article

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19 pages, 3196 KiB

Open AccessArticle

Cytotoxic Scalarane Sesterterpenes from the Sponge Hyrtios erectus

by Oh-Seok Kwon, Donghwa Kim, Chang-Kwon Kim, Jeongyoon Sun, Chung J. Sim, Dong-Chan Oh, Sang Kook Lee, Ki-Bong Oh and Jongheon Shin

Mar. Drugs 2020, 18(5), 253; https://doi.org/10.3390/md18050253 - 13 May 2020

Cited by 12 | Viewed by 3583

Abstract

Twelve new sesterterpenes along with eight known sesterterpenes were isolated from the marine sponge Hyrtios erectus collected off the coast of Chuuk Island, the Federated State of Micronesia. Based upon a combination of spectroscopic and computational analyses, these compounds were determined to be [...] Read more.

Twelve new sesterterpenes along with eight known sesterterpenes were isolated from the marine sponge Hyrtios erectus collected off the coast of Chuuk Island, the Federated State of Micronesia. Based upon a combination of spectroscopic and computational analyses, these compounds were determined to be eight glycine-bearing scalaranes (1–8), a 3-keto scalarane (9), two oxidized-furan-bearing scalaranes (10 and 11), and a salmahyrtisane (12). Several of these compounds exhibited weak antiproliferation against diverse cancer cell lines as well as moderate anti-angiogenesis activities. The antiproliferative activity of new compound 4 was found to be associated with G0/G1 arrest in the cell cycle. Full article

(This article belongs to the Special Issue Terpenoids from Marine Organisms II)

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13 pages, 2624 KiB

Open AccessArticle

Biochemical and Genomic Characterization of the Cypermethrin-Degrading and Biosurfactant-Producing Bacterial Strains Isolated from Marine Sediments of the Chilean Northern Patagonia

by Patricia Aguila-Torres, Jonathan Maldonado, Alexis Gaete, Jaime Figueroa, Alex González, Richard Miranda, Roxana González-Stegmaier, Carolina Martin and Mauricio González

Mar. Drugs 2020, 18(5), 252; https://doi.org/10.3390/md18050252 - 13 May 2020

Cited by 16 | Viewed by 4804

Abstract

Pesticides cause severe environmental damage to marine ecosystems. In the last ten years, cypermethrin has been extensively used as an antiparasitic pesticide in the salmon farming industry located in Northern Patagonia. The objective of this study was the biochemical and genomic characterization of [...] Read more.

Pesticides cause severe environmental damage to marine ecosystems. In the last ten years, cypermethrin has been extensively used as an antiparasitic pesticide in the salmon farming industry located in Northern Patagonia. The objective of this study was the biochemical and genomic characterization of cypermethrin-degrading and biosurfactant-producing bacterial strains isolated from cypermethrin-contaminated marine sediment samples collected in southern Chile (MS). Eleven strains were isolated by cypermethrin enrichment culture techniques and were identified by 16S rDNA gene sequencing analyses. The highest growth rate on cypermethrin was observed in four isolates (MS13, MS15a, MS16, and MS19) that also exhibited high levels of biosurfactant production. Genome sequence analyses of these isolates revealed the presence of genes encoding components of bacterial secondary metabolism, and the enzymes esterase, pyrethroid hydrolase, and laccase, which have been associated with different biodegradation pathways of cypermethrin. These novel cypermethrin-degrading and biosurfactant-producing bacterial isolates have a biotechnological potential for biodegradation of cypermethrin-contaminated marine sediments, and their genomes contribute to the understanding of microbial lifestyles in these extreme environments. Full article

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

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31 pages, 8647 KiB

Open AccessArticle

Inspired by Sea Urchins: Warburg Effect Mediated Selectivity of Novel Synthetic Non-Glycoside 1,4-Naphthoquinone-6S-Glucose Conjugates in Prostate Cancer

by Sergey A. Dyshlovoy, Dmitry N. Pelageev, Jessica Hauschild, Yurii E. Sabutskii, Ekaterina A. Khmelevskaya, Christoph Krisp, Moritz Kaune, Simone Venz, Ksenia L. Borisova, Tobias Busenbender, Vladimir A. Denisenko, Hartmut Schlüter, Carsten Bokemeyer, Markus Graefen, Sergey G. Polonik, Victor Ph. Anufriev and Gunhild von Amsberg

Mar. Drugs 2020, 18(5), 251; https://doi.org/10.3390/md18050251 - 11 May 2020

Cited by 24 | Viewed by 4852

Abstract

The phenomenon of high sugar consumption by tumor cells is known as Warburg effect. It results from a high glycolysis rate, used by tumors as preferred metabolic pathway even in aerobic conditions. Targeting the Warburg effect to specifically deliver sugar conjugated cytotoxic compounds [...] Read more.

The phenomenon of high sugar consumption by tumor cells is known as Warburg effect. It results from a high glycolysis rate, used by tumors as preferred metabolic pathway even in aerobic conditions. Targeting the Warburg effect to specifically deliver sugar conjugated cytotoxic compounds into tumor cells is a promising approach to create new selective drugs. We designed, synthesized, and analyzed a library of novel 6-S-(1,4-naphthoquinone-2-yl)-d-glucose chimera molecules (SABs)—novel sugar conjugates of 1,4-naphthoquinone analogs of the sea urchin pigments spinochromes, which have previously shown anticancer properties. A sulfur linker (thioether bond) was used to prevent potential hydrolysis by human glycoside-unspecific enzymes. The synthesized compounds exhibited a Warburg effect mediated selectivity to human prostate cancer cells (including highly drug-resistant cell lines). Mitochondria were identified as a primary cellular target of SABs. The mechanism of action included mitochondria membrane permeabilization, followed by ROS upregulation and release of cytotoxic mitochondrial proteins (AIF and cytochrome C) to the cytoplasm, which led to the consequent caspase-9 and -3 activation, PARP cleavage, and apoptosis-like cell death. These results enable us to further clinically develop these compounds for effective Warburg effect targeting. Full article

(This article belongs to the Special Issue Echinoderms Metabolites: Structure, Functions and Biomedical Perspectives)

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15 pages, 1604 KiB

Open AccessArticle

Optimisation of Ultrasound Frequency, Extraction Time and Solvent for the Recovery of Polyphenols, Phlorotannins and Associated Antioxidant Activity from Brown Seaweeds

by Viruja Ummat, Brijesh K Tiwari, Amit K Jaiswal, Kevin Condon, Marco Garcia-Vaquero, John O’Doherty, Colm O’Donnell and Gaurav Rajauria

Mar. Drugs 2020, 18(5), 250; https://doi.org/10.3390/md18050250 - 11 May 2020

Cited by 112 | Viewed by 7802

Abstract

This study investigates ultrasound assisted extraction (UAE) process parameters (time, frequency and solvent) to obtain high yields of phlorotannins, flavonoids, total phenolics and associated antioxidant activities from 11 brown seaweed species. Optimised UAE conditions (35 kHz, 30 min and 50% ethanol) significantly improved [...] Read more.

This study investigates ultrasound assisted extraction (UAE) process parameters (time, frequency and solvent) to obtain high yields of phlorotannins, flavonoids, total phenolics and associated antioxidant activities from 11 brown seaweed species. Optimised UAE conditions (35 kHz, 30 min and 50% ethanol) significantly improved the extraction yield from 1.5-fold to 2.2-fold in all seaweeds investigated compared to solvent extraction. Using ultrasound, the highest recovery of total phenolics (TPC: 572.3 ± 3.2 mg gallic acid equivalent/g), total phlorotannins (TPhC: 476.3 ± 2.2 mg phloroglucinol equivalent/g) and total flavonoids (TFC: 281.0 ± 1.7 mg quercetin equivalent/g) was obtained from Fucus vesiculosus seaweed. While the lowest recovery of TPC (72.6 ± 2.9 mg GAE/g), TPhC (50.3 ± 2.0 mg PGE/g) and TFC (15.2 ± 3.3 mg QE/g) was obtained from Laminaria digitata seaweed. However, extracts from Fucus serratus obtained by UAE exhibited the strongest 1,1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging activity (29.1 ± 0.25 mg trolox equivalent/g) and ferric reducing antioxidant power (FRAP) value (63.9 ± 0.74 mg trolox equivalent/g). UAE under optimised conditions was an effective, low-cost and eco-friendly technique to recover biologically active polyphenols from 11 brown seaweed species. Full article

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

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19 pages, 2933 KiB

Open AccessArticle

Carrageenan-Based Acyclovir Mucoadhesive Vaginal Tablets for Prevention of Genital Herpes

by Edisson-Mauricio Pacheco-Quito, Roberto Ruiz-Caro, Juan Rubio, Aitana Tamayo and María-Dolores Veiga

Mar. Drugs 2020, 18(5), 249; https://doi.org/10.3390/md18050249 - 11 May 2020

Cited by 29 | Viewed by 5722

Abstract

Women are the most affected by genital herpes, which is one of the most common sexually transmitted infections, affecting more than 400 million people worldwide. The application of vaginal microbicides could provide a safe method of protection. Acyclovir is a safe and effective [...] Read more.

Women are the most affected by genital herpes, which is one of the most common sexually transmitted infections, affecting more than 400 million people worldwide. The application of vaginal microbicides could provide a safe method of protection. Acyclovir is a safe and effective medication for vaginal administration, and numerous benefits have been observed in the treatment of primary or recurrent lesions due to genital herpes. Vaginal tablets based on a combination of the polymers iota-carrageenan and hydroxypropyl methylcellulose were developed for the controlled release of acyclovir. Swelling, mucoadhesion and drug release studies were carried out in simulated vaginal fluid. The tablets, containing a combination of iota-carrageenan and hydroxypropyl methylcellulose, have an adequate uptake of the medium that allows them to develop the precise consistency and volume of gel for the controlled release of acyclovir. Its high mucoadhesive capacity also allows the formulation to remain in the vaginal area long enough to ensure the complete release of acyclovir. These promising formulations for the prevention of genital herpes deserve further evaluation. Full article

(This article belongs to the Special Issue Marine Polymers in Drug Release)

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