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Mar. Drugs, Volume 17, Issue 11 (November 2019)

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Open AccessArticle
Anti-Obesity Effect of Diphlorethohydroxycarmalol Isolated from Brown Alga Ishige okamurae in High-Fat Diet-Induced Obese Mice
Mar. Drugs 2019, 17(11), 637; https://doi.org/10.3390/md17110637 (registering DOI) - 10 Nov 2019
Abstract
Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current [...] Read more.
Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases. Full article
(This article belongs to the collection Marine Drugs in the Management of Metabolic Diseases)
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Open AccessReview
A Review of Anti-Inflammatory Compounds from Marine Fungi, 2000–2018
Mar. Drugs 2019, 17(11), 636; https://doi.org/10.3390/md17110636 (registering DOI) - 09 Nov 2019
Abstract
Inflammation is a generalized, nonspecific, and beneficial host response of foreign challenge or tissue injury. However, prolonged inflammation is undesirable. It will cause loss function of involve organs, such as heat, pain redness, and swelling. Marine natural products have gained more and more [...] Read more.
Inflammation is a generalized, nonspecific, and beneficial host response of foreign challenge or tissue injury. However, prolonged inflammation is undesirable. It will cause loss function of involve organs, such as heat, pain redness, and swelling. Marine natural products have gained more and more attention due to their unique mechanism of anti-inflammatory action, and have considered a hotspot for anti-inflammatory drug development. Marine-derived fungi are promising sources of structurally unprecedented bioactive natural products. So far, a plethora of new secondary metabolites with anti-inflammatory activities from marine-derived fungi had been widely reported. This review covers 133 fungal metabolites described in the period of 2000 to 2018, including the structures and origins of these secondary metabolites. Full article
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Open AccessArticle
Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia
Mar. Drugs 2019, 17(11), 635; https://doi.org/10.3390/md17110635 - 08 Nov 2019
Abstract
In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung [...] Read more.
In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS1) as well as product/daughter ions (MS2) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential. Full article
(This article belongs to the Special Issue Marine Bacteria as Sources of Bioactive Compounds)
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Open AccessArticle
Deacetylphylloketal, a New Phylloketal Derivative from a Marine Sponge, Genus Phyllospongia, with Potent Anti-Inflammatory Activity in In Vitro Co-Culture Model of Intestine
Mar. Drugs 2019, 17(11), 634; https://doi.org/10.3390/md17110634 - 08 Nov 2019
Abstract
The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the [...] Read more.
The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1β and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD. Full article
(This article belongs to the Special Issue Marine Immunomodulators)
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Open AccessArticle
Quantitative Structure-Activity Relationship Model to Predict Antioxidant Effects of the Peptide Fraction Extracted from a Co-Culture System of Chlorella pyrenoidosa and Yarrowia lipolytica
Mar. Drugs 2019, 17(11), 633; https://doi.org/10.3390/md17110633 - 08 Nov 2019
Abstract
In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed [...] Read more.
In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed of hydrophobic amino acids (48.1%). These peptides showed remarkable protective effects against oxidative stress in HepG2, which may be attributed to their structures. Furthermore, the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly lower in the peptide-treated group than in the control group, suggesting that the antioxidant enzyme-coding genes were not activated. The EC50 value of three peptides in the EHPs were in the order of AGYSPIGFVR (0.04 ± 0.002 mg/mL) > VLDELTLAR (0.09 ± 0.001 mg/mL) > LFDPVYLFDQG (0.41 ± 0.03 mg/mL); these results agreed with the prediction of the model (R2 > 0.9, Q2 > 0.5). Thus, EHPs show potential as potent new antioxidant agents. Full article
(This article belongs to the Special Issue Strategies for Enhancing the Metabolome of Marine-Derived Fungi)
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Open AccessArticle
Anti-aging Effect of Agar Oligosaccharide on Male Drosophila melanogaster and its Preliminary Mechanism
Mar. Drugs 2019, 17(11), 632; https://doi.org/10.3390/md17110632 - 06 Nov 2019
Abstract
Agar oligosaccharide (AOS) is a marine prebiotic with apparent anti-inflammatory, antioxidant and anti-tumor effects. During this study, different doses of AOS are added to a basal diet to evaluate its effects on the lifespan, motor vigor and reproduction of male Drosophila melanogaster. [...] Read more.
Agar oligosaccharide (AOS) is a marine prebiotic with apparent anti-inflammatory, antioxidant and anti-tumor effects. During this study, different doses of AOS are added to a basal diet to evaluate its effects on the lifespan, motor vigor and reproduction of male Drosophila melanogaster. Additionally, the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase (CAT) and the malondialdehyde (MDA) content in male Drosophila are examined on the 10th, 25th and 40th days. The fly midguts are removed on the 10th and 40th days for analyses of the intestinal microbial community by 16S rDNA sequencing and the expression level of intestinal immunity genes by quantitative real-time PCR (RT-PCR). The results show that AOS significantly prolonged the average and maximum lifespan and increased the antioxidant capacity of male Drosophila. Additionally, AOS significantly regulated the structure of the intestinal flora of "old" flies (40 days) and upregulated the expression of immune deficiency (IMD) genes to improve the intestinal immunity, which could be beneficial for delaying aging in old flies. The above-described results provide a theoretical basis for the application of AOS, a type of marine oligosaccharide, as a nutritional supplement or immunomodulator. Full article
(This article belongs to the Special Issue Marine Antioxidant)
Open AccessArticle
Structures and Bioactivities of Psolusosides B1, B2, J, K, L, M, N, O, P, and Q from the Sea Cucumber Psolus fabricii. The First Finding of Tetrasulfated Marine Low Molecular Weight Metabolites
Mar. Drugs 2019, 17(11), 631; https://doi.org/10.3390/md17110631 - 06 Nov 2019
Abstract
Ten new di-, tri- and tetrasulfated triterpene glycosides, psolusosides B1 (1), B2 (2), J (3), K (4), L (5), M (6), N (7), O (8), [...] Read more.
Ten new di-, tri- and tetrasulfated triterpene glycosides, psolusosides B1 (1), B2 (2), J (3), K (4), L (5), M (6), N (7), O (8), P (9), and Q (10), were isolated from the sea cucumber Psolus fabricii collected in the Sea of Okhotsk near the Kurile Islands. Structures of these glycosides were established by two-dimensional (2D) NMR spectroscopy and HR-ESI mass-spectrometry. It is particularly interesting that highly polar compounds 9 and 10 contain four sulfate groups in their carbohydrate moieties, including two sulfates in the same terminal glucose residue. Glycoside 2 has an unusual non-holostane aglycone with 18(16)-lactone and a unique 7,8-epoxy fragment. Cytotoxic activities of compounds 110 against several mouse cell lines such as Ehrlich ascites carcinoma cells, neuroblastoma Neuro 2A, normal epithelial JB-6 cells, and erythrocytes were quite different depending both on structural peculiarities of these glycosides and the type of cells subjected to their actions. Psolusoside L (5), pentaoside, with three sulfate groups at C-6 of two glucose and one 3-O-methylglucose residue and holostane aglycone, is the most active compound in the series. The presence of a sulfate group at C-2 of the terminal glucose residue attached to C-4 of the first (xylose) residue significantly decreases activities of the corresponding glycosides. Psolusosides of group B (1, 2, and known psolusoside B) are inactive in all tests due to the presence of non-holostane aglycones and tetrasaccharide-branched sugar chains sulfated by C-2 of Glc4. Full article
(This article belongs to the Special Issue Marine Glycoconjugates: Trends and Perspectives)
Open AccessFeature PaperArticle
Variation in Lipid Components from 15 Species of Tropical and Temperate Seaweeds
Mar. Drugs 2019, 17(11), 630; https://doi.org/10.3390/md17110630 - 06 Nov 2019
Abstract
The present study describes the variation in lipid components from 15 species of seaweeds belonging to the Chlorophyta, Ochrophyta, and Rhodophyta phyla collected in tropical (Indonesia) and temperate (Japan) areas. Analyses were performed of multiple components, including chlorophylls, carotenoids, n-3 and n-6 polyunsaturated [...] Read more.
The present study describes the variation in lipid components from 15 species of seaweeds belonging to the Chlorophyta, Ochrophyta, and Rhodophyta phyla collected in tropical (Indonesia) and temperate (Japan) areas. Analyses were performed of multiple components, including chlorophylls, carotenoids, n-3 and n-6 polyunsaturated fatty acids (PUFAs), and alpha tocopherol (α-Toc). Chlorophyll (Chl) and carotenoid contents varied among phyla, but not with the sampling location. Chl a and b were the major chlorophylls in Chlorophyta. Chl a and Chl c were the main chlorophylls in Ochrophyta, while Chl a was the dominant chlorophylls in Rhodophyta. β-Carotene and fucoxanthin were detected as major seaweed carotenoids. The former was present in all species in a variety of ranges, while the latter was mainly found in Ochrophyta and in small quantities in Rhodophyta, but not in Chlorophyta. The total lipids (TL) content and fatty acids composition were strongly affected by sampling location. The TL and n-3 PUFAs levels tended to be higher in temperate seaweeds compared with those in tropical seaweeds. The major n-3 PUFAs in different phyla, namely, eicosapentaenoic acid (EPA) and stearidonic acid (SDA) in Ochrophyta, α-linolenic acid (ALA) and SDA in Chlorophyta, and EPA in Rhodophyta, accumulated in temperate seaweeds. Chlorophylls, their derivatives, and carotenoids are known to have health benefits, such as antioxidant activities, while n-3 PUFAs are known to be essential nutrients that positively influence human nutrition and health. Therefore, seaweed lipids could be used as a source of ingredients with health benefits for functional foods and nutraceuticals. Full article
(This article belongs to the Special Issue Characterization of Bioactive Components in Edible Algae)
Open AccessArticle
Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions
Mar. Drugs 2019, 17(11), 629; https://doi.org/10.3390/md17110629 - 06 Nov 2019
Abstract
We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300–400 nm range. Results [...] Read more.
We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300–400 nm range. Results showed that these CD bands do not originate from intrinsic STC chirality but are a specific property of a peculiar aggregation process similar to psi-DNA CD response. Transmission electron microscopy (TEM) experiments revealed a fine fiber network resembling a supramolecular gel structure with helical fibers. Thermodynamic studies of aggregates by differential scanning calorimetry (DSC) revealed high reversibility of the dominant aggregation process. We demonstrated that the novel STC psi-CD band at 345 nm could be applied at biorelevant conditions (100 nanomolar concentration) and even in marine-salt content conditions for specific and quantitative monitoring of STC. Also, we showed that STC strongly non-covalently interacts with ds-DNA with likely toxic effects, thus contrary to the previous belief requiring prior enzyme epoxidation. Full article
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Open AccessArticle
Effects of Astaxanthin from Shrimp Shell on Oxidative Stress and Behavior in Animal Model of Alzheimer’s Disease
Mar. Drugs 2019, 17(11), 628; https://doi.org/10.3390/md17110628 - 04 Nov 2019
Abstract
This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp (Litopenaeus vannamei) shells on Wistar rats with Alzheimer’s disease, induced by amyloid-β (1-42) peptides. In this task, the rats were divided into eight groups: (1) [...] Read more.
This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp (Litopenaeus vannamei) shells on Wistar rats with Alzheimer’s disease, induced by amyloid-β (1-42) peptides. In this task, the rats were divided into eight groups: (1) Control, (2) sham operate, (3) negative control (vehicle) + Aβ1-42, (4) ASX extract+Aβ1-42, (5) commercial ASX + Aβ1-42, (6) ASX powder + Aβ1-42, (7) blank powder + Aβ1-42, and (8) vitamin E + Aβ1-42. All treatments were orally administrated for 30 days. At 14- and 29-days post injection, animals were observed in behavioral tests. On the 31st day, animals were sacrificed; the hippocampus and cortex were collected. Those two brain areas were then homogenized and stored for biochemical and histological analysis. The results showed that the Aβ1-42 infused group significantly reduced cognitive ability and increased memory loss, as assessed by the Morris water maze test, novel object recognition test, and novel object location test. Moreover, the Aβ1-42 infused group exhibited a deterioration of oxidative markers, including glutathione peroxidase enzymes (GPx), lipid peroxidation (MDA), products of protein oxidation, and superoxide anion in the cortex and the hippocampus. Meanwhile, ASX powder (10 mg/kg body weight) showed a significant reduction in cognitive and memory impairments and oxidative stress which is greater than ASX extract in the same dose of compound or vitamin E (100 mg/kg body weight). Our study indicates the beneficial properties of ASX in alleviation of cognitive functions and reducing neurodegeneration in Wistar rats induced by amyloid-β (1-42) peptides. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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Open AccessArticle
Development and Characterization of Astaxanthin-Containing Whey Protein-Based Nanoparticles
Mar. Drugs 2019, 17(11), 627; https://doi.org/10.3390/md17110627 - 04 Nov 2019
Abstract
Astaxanthin (ASX) is a carotenoid of great interest due to its potential health benefits. However, its use in the food, feed, and pharmaceutical fields is limited due to low bioavailability, poor stability during thermochemical treatments, susceptibility to oxidation, and poor organoleptic characteristics. The [...] Read more.
Astaxanthin (ASX) is a carotenoid of great interest due to its potential health benefits. However, its use in the food, feed, and pharmaceutical fields is limited due to low bioavailability, poor stability during thermochemical treatments, susceptibility to oxidation, and poor organoleptic characteristics. The aim of this work was to develop a method to stabilize astaxanthin extracted from the microalgae Haematococcus pluvialis (H.p.) and to improve its nutritional and functional properties through nanoencapsulation. Nanoparticles (NPs) were produced by emulsification–solvent evaporation technique starting from H.p. oleoresin using whey proteins concentrate (WPC) as stabilizer. The efficiency of encapsulation was 96%. The particle size (Z-average) was in the range of 80–130 nm and the superficial charge (measured as zeta-potential) was negative (−20 to −30 mV). The stability of the NPs upon resuspension in water was assayed through a panel of stress tests, i.e., extreme pH, UV radiation, Fe3+ exposition, and heating at 65 °C, that always showed a superior performance of encapsulated ASX in comparison to oleoresin, even if NPs tended to precipitate at pH 3.5–5.5. Simulated gastroenteric digestion was conducted to study the release of ASX in physiological conditions, and showed a maximum bioaccessibility of 76%, with 75% ASX converted into the more bioavailable free form. The collected data suggest that NPs might have possible future applications as supplements for human and animal diets. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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Open AccessArticle
Effect of Carboxymethylation and Phosphorylation on the Properties of Polysaccharides from Sepia esculenta Ink: Antioxidation and Anticoagulation in Vitro
Mar. Drugs 2019, 17(11), 626; https://doi.org/10.3390/md17110626 - 01 Nov 2019
Abstract
To investigate the effect of carboxymethylation and phosphorylation modification on Sepia esculenta ink polysaccharide (SIP) properties, this study prepared carboxymethyl SIP (CSIP) with the chloracetic acid method, and phosphorylated SIP (PSIP) with the sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) method, on the basis of [...] Read more.
To investigate the effect of carboxymethylation and phosphorylation modification on Sepia esculenta ink polysaccharide (SIP) properties, this study prepared carboxymethyl SIP (CSIP) with the chloracetic acid method, and phosphorylated SIP (PSIP) with the sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) method, on the basis of an orthogonal experiment. The in vitro antioxidant and anticoagulant activities of the derivatives were determined by assessing the scavenging capacity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals, which activated the partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results showed that SIP was modified successfully to be CSIP and PSIP, and degrees of substitution (DSs) of the two products were 0.9913 and 0.0828, respectively. Phosphorylation efficiently improved the antioxidant property of SIP, and the IC50 values of PSIP on DPPH and hydroxyl radicals decreased by 63.25% and 13.77%, respectively. But carboxymethylation reduced antioxidant activity of the native polysaccharide, IC50 values of CSIP on the DPPH and hydroxyl radicals increased by 16.74% and 6.89%, respectively. SIP significantly prolonged the APTT, PT, and TT in a dose-dependent fashion, suggesting that SIP played an anticoagulant action through intrinsic, extrinsic, and common coagulation pathways. CSIP and PSIP both possessed a stronger anticoagulant capacity than SIP via the same pathways; moreover, CSIP was observed to be more effective in prolonging APTT and PT than PSIP. Full article
(This article belongs to the collection Marine Polysaccharides) Printed Edition available
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Open AccessArticle
Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells
Mar. Drugs 2019, 17(11), 625; https://doi.org/10.3390/md17110625 - 01 Nov 2019
Abstract
Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the [...] Read more.
Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the screening of microalgae for potential pharmaceutical applications. Here, we show that monoacylglycerides (MAGs) purified from the marine diatom Skeletonema marinoi have selective cytotoxic activity against the haematological cancer cell line U-937 and colon cancer cell line HCT-116 compared to normal MePR-2B cells. LC-MS analysis of the raw extract revealed that in their natural form, MAGs occur as 2-monoacyl derivatives and include mainly C16 and C20 analogues, but they are converted into the corresponding 1-isomers during purification processes. Pure compounds along with the synthetic 1-monoarachidonoylglycerol tested on HCT-116 and U-937 tumor cell lines induced cell death via apoptosis. The mechanism of action was investigated, and we show that it involves the induction of apoptosis through caspase 3/7 activation. These findings pave the way for the possible use of these molecules as potential anticancer agents or as precursors for the generation of new and more potent and selective compounds against tumor cells. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Open AccessArticle
Computational Tools in the Discovery of FABP4 Ligands: A Statistical and Molecular Modeling Approach
Mar. Drugs 2019, 17(11), 624; https://doi.org/10.3390/md17110624 - 31 Oct 2019
Abstract
Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have received interest following the recent publication of their pharmacologically beneficial effects. Recently, it was revealed that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, [...] Read more.
Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have received interest following the recent publication of their pharmacologically beneficial effects. Recently, it was revealed that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, and some type of cancers. In past years, hundreds of effective FABP4 inhibitors have been synthesized and discovered, but, unfortunately, none have reached the clinical research phase. The field of computer-aided drug design seems to be promising and useful for the identification of FABP4 inhibitors; hence, different structure- and ligand-based computational approaches have been used for their identification. In this paper, we searched for new potentially active FABP4 ligands in the Marine Natural Products (MNP) database. We retrieved 14,492 compounds from this database and filtered through them with a statistical and computational filter. Seven compounds were suggested by our methodology to possess a potential inhibitory activity upon FABP4 in the range of 97–331 nM. ADMET property prediction was performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives. From these analyses, three molecules that are excellent candidates for becoming new drugs were found. Full article
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Open AccessArticle
Sediment as a Potential Pool for Lipophilic Marine Phycotoxins with the Case Study of Daya Bay of China
Mar. Drugs 2019, 17(11), 623; https://doi.org/10.3390/md17110623 - 31 Oct 2019
Abstract
Marine sediments can reserve many environmental pollutants. Lipophilic marine phycotoxins (LMPs) are natural toxic substances widespread in the marine environment; however, evidence of their existence in sediment is scarce. In the present study, in order to explore the occurrence and distribution characteristics of [...] Read more.
Marine sediments can reserve many environmental pollutants. Lipophilic marine phycotoxins (LMPs) are natural toxic substances widespread in the marine environment; however, evidence of their existence in sediment is scarce. In the present study, in order to explore the occurrence and distribution characteristics of LMPs in sediment, surface sediment samples collected from a tropical area of Daya Bay (DYB) at different seasons, were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). According to the results, up to six toxin compounds were detected in sediment samples from DYB, OA and DTX1 had the highest levels, followed by PTX2, homo-YTX, AZA2, and GYM. Although AZA2 and GYM were found in most of the sediment, OA, DTX1, homo-YTX, and PTX2 were the predominant toxin compounds, and PTX2 was the most ubiquitous toxin in sediment. The spatial distribution of LMP components in the sediment fluctuated with sampling times, partially according to the physical–chemical parameters of the sediment. There are likely several sources for LMPs existing in surface sediments, but it is difficult to determine contributions of a specific toxin-source in the sediment. Therefore, marine sediments may be a toxin reservoir for LMPs accumulation in benthic organisms via food chains. Full article
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Open AccessArticle
Echinochrome A Reduces Colitis in Mice and Induces In Vitro Generation of Regulatory Immune Cells
Mar. Drugs 2019, 17(11), 622; https://doi.org/10.3390/md17110622 - 31 Oct 2019
Abstract
Echinochrome A (Ech A), a natural pigment extracted from sea urchins, is the active ingredient of a marine-derived pharmaceutical called ‘histochrome’. Since it exhibits several biological activities including anti-oxidative and anti-inflammatory effects, it has been applied to the management of cardiac injury and [...] Read more.
Echinochrome A (Ech A), a natural pigment extracted from sea urchins, is the active ingredient of a marine-derived pharmaceutical called ‘histochrome’. Since it exhibits several biological activities including anti-oxidative and anti-inflammatory effects, it has been applied to the management of cardiac injury and ocular degenerative disorders in Russia and its protective role has been studied for other pathologic conditions. In the present study, we sought to investigate the therapeutic potential of Ech A for inflammatory bowel disease (IBD) using a murine model of experimental colitis. We found that intravenous injection of Ech A significantly prevented body weight loss and subsequent lethality in colitis-induced mice. Interestingly, T cell proliferation was significantly inhibited upon Ech A treatment in vitro. During the helper T (Th) cell differentiation process, Ech A stimulated the generation regulatory T (Treg) cells that modulate the inflammatory response and immune homeostasis. Moreover, Ech A treatment suppressed the in vitro activation of pro-inflammatory M1 type macrophages, while inducing the production of M2 type macrophages that promote the resolution of inflammation and initiate tissue repair. Based on these results, we suggest that Ech A could provide a beneficial impact on IBD by correcting the imbalance in the intestinal immune system. Full article
(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)
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Open AccessArticle
Improved Astaxanthin Production with Corynebacterium glutamicum by Application of a Membrane Fusion Protein
Mar. Drugs 2019, 17(11), 621; https://doi.org/10.3390/md17110621 - 31 Oct 2019
Abstract
Astaxanthin is one of the strongest natural antioxidants and a red pigment occurring in nature. This C40 carotenoid is used in a broad range of applications such as a colorant in the feed industry, an antioxidant in cosmetics or as a supplement in [...] Read more.
Astaxanthin is one of the strongest natural antioxidants and a red pigment occurring in nature. This C40 carotenoid is used in a broad range of applications such as a colorant in the feed industry, an antioxidant in cosmetics or as a supplement in human nutrition. Natural astaxanthin is on the rise and, hence, alternative production systems are needed. The natural carotenoid producer Corynebacterium glutamicum is a potent host for industrial fermentations, such as million-ton scale amino acid production. In C. glutamicum, astaxanthin production was established through heterologous overproduction of the cytosolic lycopene cyclase CrtY and the membrane-bound β-carotene hydroxylase and ketolase, CrtZ and CrtW, in previous studies. In this work, further metabolic engineering strategies revealed that the potential of this GRAS organism for astaxanthin production is not fully exploited yet. It was shown that the construction of a fusion protein comprising the membrane-bound β-carotene hydroxylase and ketolase (CrtZ~W) significantly increased astaxanthin production under high glucose concentration. An evaluation of used carbon sources indicated that a combination of glucose and acetate facilitated astaxanthin production. Moreover, additional overproduction of cytosolic carotenogenic enzymes increased the production of this high value compound. Taken together, a seven-fold improvement of astaxanthin production was achieved with 3.1 mg/g CDW of astaxanthin. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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Open AccessReview
Successful Approaches for a Red Seaweed Biorefinery
Mar. Drugs 2019, 17(11), 620; https://doi.org/10.3390/md17110620 - 30 Oct 2019
Abstract
Macroalgae have been commercially exploited as food and for the production of phycocolloids, but they also contain compounds with potential in pharmaceutical, nutraceutical, cosmetic, chemical and energetic applications. The biorefinery concept applied to seaweed facilitates the extraction of different constituents ensuring full utilization [...] Read more.
Macroalgae have been commercially exploited as food and for the production of phycocolloids, but they also contain compounds with potential in pharmaceutical, nutraceutical, cosmetic, chemical and energetic applications. The biorefinery concept applied to seaweed facilitates the extraction of different constituents ensuring full utilization of resources and generating few residues through a succession of steps. Seaweed biorefineries are less advanced than those based on terrestrial biomass and the design of efficient processes requires further study. This review presents practical successful examples to obtain two or more commercially valuable components from red seaweeds. The selected processes consist on cascading stages of both conventional and alternative techniques to illustrate different possible valorization strategies. Full article
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Open AccessArticle
Lemnalol Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes
Mar. Drugs 2019, 17(11), 619; https://doi.org/10.3390/md17110619 - 30 Oct 2019
Abstract
Sepsis, an inflammatory response to infection provoked by lipopolysaccharide (LPS), is associated with high mortality, as well as ischemic stroke and new-onset atrial arrhythmia. Severe bacterial infections causing sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic [...] Read more.
Sepsis, an inflammatory response to infection provoked by lipopolysaccharide (LPS), is associated with high mortality, as well as ischemic stroke and new-onset atrial arrhythmia. Severe bacterial infections causing sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic multi-organ dysfunction and finally death. LPS challenge-induced inflammatory responses during sepsis may increase the likelihood of the arrhythmogenesis. Lemnalol is known to possess potent anti-inflammatory effects. This study examined whether Lemnalol (0.1 μM) could modulate the electrophysiological characteristics and calcium homeostasis of atrial myocytes under the influence of LPS (1μg/mL). Under challenge with LPS, Lemnalol-treated LA myocytes, had a longer AP duration at 20%, 50% and 90% repolarization of the amplitude, compared to the LPS-treated cells. LPS-challenged LA myocytes showed increased late sodium current, Na+-Ca2+ exchanger current, transient outward current, rapid component of delayed rectifier potassium current, tumor necrosis factor-α, NF-κB and increased phosphorylation of ryanodine receptor (RyR), but a lower L-type Ca2+ current than the control LA myocytes. Exposure to Lemnalol reversed the LPS-induced effects. The LPS-treated and control groups of LA myocytes, with or without the existence of Lemnalol. showed no apparent alterations in the sodium current amplitude or Cav1.2 expression. The expression of sarcoendoplasmic reticulum calcium transport ATPase (SERCA2) was reduced by LPS treatment, while Lemnalol ameliorated the LPS-induced alterations. The phosphorylation of RyR was enhanced by LPS treatment, while Lemnalol attenuated the LPS-induced alterations. In conclusion, Lemnalol modulates LPS-induced alterations of LA calcium homeostasis and blocks the NF-κB pathways, which may contribute to the attenuation of LPS-induced arrhythmogenesis. Full article
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Open AccessArticle
Fast Detection of Two Smenamide Family Members Using Molecular Networking
Mar. Drugs 2019, 17(11), 618; https://doi.org/10.3390/md17110618 - 30 Oct 2019
Abstract
Caribbean sponges of the genus Smenospongia are a prolific source of chlorinated secondary metabolites. The use of molecular networking as a powerful dereplication tool revealed in the metabolome of S. aurea two new members of the smenamide family, namely smenamide F (1 [...] Read more.
Caribbean sponges of the genus Smenospongia are a prolific source of chlorinated secondary metabolites. The use of molecular networking as a powerful dereplication tool revealed in the metabolome of S. aurea two new members of the smenamide family, namely smenamide F (1) and G (2). The structure of smenamide F (1) and G (2) was determined by spectroscopic analysis (NMR, MS, ECD). The relative and the absolute configuration at C-13, C-15, and C-16 was determined on the basis of the conformational rigidity of a 1,3-disubstituted alkyl chain system (i.e., the C-12/C-18 segment of compound (1). Smenamide F (1) and G (2) were shown to exert a selective moderate antiproliferative activity against cancer cell lines MCF-7 and MDA-MB-231, while being inactive against MG-63. Full article
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Open AccessReview
Bright Spots in the Darkness of Cancer: A Review of Starfishes-Derived Compounds and Their Anti-Tumor Action
Mar. Drugs 2019, 17(11), 617; https://doi.org/10.3390/md17110617 - 29 Oct 2019
Abstract
The fight against cancer represents a great challenge for researchers and, for this reason, the search for new promising drugs to improve cancer treatments has become inevitable. Oceans, due to their wide diversity of marine species and environmental conditions have proven to be [...] Read more.
The fight against cancer represents a great challenge for researchers and, for this reason, the search for new promising drugs to improve cancer treatments has become inevitable. Oceans, due to their wide diversity of marine species and environmental conditions have proven to be precious sources of potential natural drugs with active properties. As an example, in this context several studies performed on sponges, tunicates, mollusks, and soft corals have brought evidence of the interesting biological activities of the molecules derived from these species. Also, echinoderms constitute an important phylum, whose members produce a huge number of compounds with diverse biological activities. In particular, this review is the first attempt to summarize the knowledge about starfishes and their secondary metabolites that exhibited a significant anticancer effect against different human tumor cell lines. For each species of starfish, the extracted molecules, their effects, and mechanisms of action are described. Full article
(This article belongs to the Special Issue Antitumor Compounds from Marine Invertebrates)
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Open AccessArticle
Virescenosides from the Holothurian-Associated Fungus Acremonium striatisporum Kmm 4401
Mar. Drugs 2019, 17(11), 616; https://doi.org/10.3390/md17110616 - 29 Oct 2019
Abstract
Ten new diterpene glycosides virescenosides Z9-Z18 (110) together with three known analogues (1113) and aglycon of virescenoside A (14) were isolated from the marine-derived fungus Acremonium striatisporum KMM 4401. These [...] Read more.
Ten new diterpene glycosides virescenosides Z9-Z18 (110) together with three known analogues (1113) and aglycon of virescenoside A (14) were isolated from the marine-derived fungus Acremonium striatisporum KMM 4401. These compounds were obtained by cultivating fungus on wort agar medium with the addition of potassium bromide. Structures of the isolated metabolites were established based on spectroscopic methods. The effects of some isolated glycosides and aglycons 1518 on urease activity and regulation of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) production in macrophages stimulated with lipopolysaccharide (LPC) were evaluated. Full article
(This article belongs to the Special Issue Marine Glycoconjugates: Trends and Perspectives)
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Open AccessArticle
Dietary Supplementation with the Red Seaweed Porphyra umbilicalis Protects against DNA Damage and Pre-Malignant Dysplastic Skin Lesions in HPV-Transgenic Mice
Mar. Drugs 2019, 17(11), 615; https://doi.org/10.3390/md17110615 - 29 Oct 2019
Abstract
Some diet profiles are associated with the risk of developing cancer; however, some nutrients show protective effects. Porphyra umbilicalis is widely consumed, having a balanced nutritional profile; however, its potential for cancer chemoprevention still needs comprehensive studies. In this study, we incorporated P. [...] Read more.
Some diet profiles are associated with the risk of developing cancer; however, some nutrients show protective effects. Porphyra umbilicalis is widely consumed, having a balanced nutritional profile; however, its potential for cancer chemoprevention still needs comprehensive studies. In this study, we incorporated P. umbilicalis into the diet of mice transgenic for the human papillomavirus type 16 (HPV16), which spontaneously develop pre-malignant and malignant lesions, and determined whether this seaweed was able to block lesion development. Forty-four 20-week-old HPV+/− and HPV−/− mice were fed either a base diet or a diet supplemented with 10% seaweed. At the end of the study, skin samples were examined to classify HPV16-induced lesions. The liver was also screened for potential toxic effects of the seaweed. Blood was used to study toxicological parameters and to perform comet and micronucleus genotoxicity tests. P. umbilicalis significantly reduced the incidence of pre-malignant dysplastic lesions, completely abrogating them in the chest skin. These results suggest that P. umbilicalis dietary supplementation has the potential to block the development of pre-malignant skin lesions and indicate its antigenotoxic activity against HPV-induced DNA damage. Further studies are needed to establish the seaweed as a functional food and clarify the mechanisms whereby this seaweed blocks multistep carcinogenesis induced by HPV. Full article
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Open AccessArticle
Investigation of the Possible Pharmacologically Active Forms of the Nicotinic Acetylcholine Receptor Agonist Anabaseine
Mar. Drugs 2019, 17(11), 614; https://doi.org/10.3390/md17110614 - 29 Oct 2019
Abstract
Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the monocationic open-chain ammonium-ketone) co-exist in almost equal concentrations at physiological pH. We asked the question: Which of these forms is pharmacologically active? First, we investigated the pH dependence [...] Read more.
Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the monocationic open-chain ammonium-ketone) co-exist in almost equal concentrations at physiological pH. We asked the question: Which of these forms is pharmacologically active? First, we investigated the pH dependence of anabaseine inhibition of [3H]-methylcarbamylcholine binding at rat brain α4β2 nicotinic acetylcholine receptors (nAChRs). These experiments indicated that one or both monocationic forms interact with the orthosteric binding site for ACh. However, since they occur at equal concentrations near physiological pH, we employed another approach, preparing a stable analog of each form and examining its agonist activities and binding affinities at several vertebrate brain and neuromuscular nAChRs. Only 2-(3-pyridyl)-1,4,5,6-tetrahydropyrimidine monohydrogen chloride (PTHP), the cyclic iminium analog, displayed nAChR potencies and binding affinities similar to anabaseine. The cyclic imine analog 2,3′-bipyridyl and the open-chain ammonium-ketone analog 5-methylamino-1-(3-pyridyl)-1-pentanone (MAPP), displayed ≤1% of the activity predicted if the one form was solely active. The lower potency of weakly basic 2,3′-bipyridyl can be explained by the presence of a small concentration of its monocationic form. Since the open chain ammonium-ketone monocationic form of anabaseine has some structural similarity to the neurotransmitter GABA, we also tested the ability of anabaseine and its 1,2-dehydropyrrolidinyl analog myosmine to activate a mammalian GABAA receptor, but no activity was detected. We conclude that the monocationic cyclic iminium is the form which avidly binds and activates vertebrate nAChRs. Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
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Open AccessReview
Antihypertensive and Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Fish as Potential Cardioprotective Compounds
Mar. Drugs 2019, 17(11), 613; https://doi.org/10.3390/md17110613 - 29 Oct 2019
Abstract
The term metabolic/cardiometabolic/insulin resistance syndrome could generally be defined as the co-occurrence of several risk factors inclusive of systemic arterial hypertension. Not only that organizations, such as the world health organization (WHO) have identified high blood pressure as one of the main risk [...] Read more.
The term metabolic/cardiometabolic/insulin resistance syndrome could generally be defined as the co-occurrence of several risk factors inclusive of systemic arterial hypertension. Not only that organizations, such as the world health organization (WHO) have identified high blood pressure as one of the main risk factors of the cardiometabolic syndrome, but there is also a link between the occurrence of insulin resistance/impaired glucose tolerance and hypertension that would consequently lead to type-2 diabetes (T2D). Hypertension is medicated by various classes of synthetic drugs; however, severe or mild adverse effects have been repeatedly reported. To avoid and reduce these adverse effects, natural alternatives, such as bioactive peptides derived from different sources have drawn the attention of researchers. Among all types of biologically active peptides inclusive of marine-derived ones, this paper’s focus would solely be on fish and fishery by-processes’ extracted peptides and products. Isolation and fractionation processes of these products alongside their structural, compositional and digestion stability characteristics have likewise been briefly discussed to better address the structure-activity relationship, expanding the reader’s knowledge on research and discovery trend of fish antihypertensive biopeptides. Furthermore, drug-likeness of selected biopeptides was predicted by Lipinski’s rules to differentiate a drug-like biopeptide from nondrug-like one. Full article
(This article belongs to the collection Marine Drugs in the Management of Metabolic Diseases)
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Open AccessArticle
Pyrogallol-Phloroglucinol-6,6-Bieckol Alleviates Obesity and Systemic Inflammation in a Mouse Model by Reducing Expression of RAGE and RAGE Ligands
Mar. Drugs 2019, 17(11), 612; https://doi.org/10.3390/md17110612 - 28 Oct 2019
Abstract
Ecklonia cava (E. cava) can alleviate diet-induced obesity in animal models, and phlorotannins contained in E. cava help prevent hypertrophy-induced adipocyte differentiation. Receptor for advanced glycation end-products (RAGE) is well known to induce hypertrophy of visceral fat and to trigger inflammation [...] Read more.
Ecklonia cava (E. cava) can alleviate diet-induced obesity in animal models, and phlorotannins contained in E. cava help prevent hypertrophy-induced adipocyte differentiation. Receptor for advanced glycation end-products (RAGE) is well known to induce hypertrophy of visceral fat and to trigger inflammation substantially. While the relationship between RAGE and obesity and inflammation has been well-characterized, few studies describe the effects of phlorotannin on RAGE. In this study, we investigated the anti-obesity effects of pyrogallol-phloroglucinol-6,6-bieckol (PPB)—a single compound from the ethanoic extract of E. cava—mediated by a reduction in the inflammation caused by RAGE and RAGE ligands. In visceral fat, PPB (i) significantly inhibited RAGE ligands, (ii) reduced the expression of RAGE, and (iii) reduced the binding ratio between RAGE and RAGE ligands. Under lower expression of RAGE, RAGE ligands and their cognate binding, the differentiation of macrophages found in visceral fat into M1-type—the pro-inflammatory form of this immune cell—was reduced. As the M1-type macrophage decreased, pro-inflammatory cytokines, which cause obesity, decreased in visceral fat. The results of this study highlight the anti-obesity effects of PPB, with the effects mediated by reductions in RAGE, RAGE ligands, and inflammation. Full article
(This article belongs to the collection Marine Drugs in the Management of Metabolic Diseases)
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Open AccessArticle
Mineral-Enriched Deep-Sea Water Modulates Lactate Metabolism via PGC-1α-Mediated Metabolic Reprogramming
Mar. Drugs 2019, 17(11), 611; https://doi.org/10.3390/md17110611 - 27 Oct 2019
Abstract
Metabolic disorders such as diabetes and obesity are serious global health issues. These diseases are accelerated by mineral deficiencies, emphasizing the importance of addressing these deficiencies in disease management plans. Lactate metabolism is fundamentally linked to glucose metabolism, and several clinical studies have [...] Read more.
Metabolic disorders such as diabetes and obesity are serious global health issues. These diseases are accelerated by mineral deficiencies, emphasizing the importance of addressing these deficiencies in disease management plans. Lactate metabolism is fundamentally linked to glucose metabolism, and several clinical studies have reported that blood lactate levels are higher in obese and diabetic patients than in healthy subjects. Balanced deep-sea water contains various minerals and exhibits antiobesity and antidiabetic activities in mice; however, the impact of balanced deep-sea water on lactate metabolism is unclear. Thus, we evaluated the effects of balanced deep-sea water on lactate metabolism in C2C12 myotubes, and found that balanced deep-sea water mediated lactate metabolism by regulating the gene expression levels of lactate dehydrogenases A and B, a monocarboxylate transporter, and a mitochondrial pyruvate carrier. The activities of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and signaling molecules involved in PGC-1α activation were also upregulated by treatment with balanced deep-sea water. These results suggest that balanced deep-sea water, which can mediate lactate metabolism, may be used to prevent or treat obesity and diabetes mellitus. Full article
(This article belongs to the Special Issue Deep-Sea Natural Products II)
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Open AccessArticle
Nutraceutical Extract from Dulse (Palmaria palmata L.) Inhibits Primary Human Neutrophil Activation
Mar. Drugs 2019, 17(11), 610; https://doi.org/10.3390/md17110610 - 25 Oct 2019
Abstract
Palmaria palmata L. (Palmariaceae), commonly known as “dulse”, is a red alga that grows on the northern coasts of the Atlantic and Pacific oceans, and is widely used as source of fiber and protein. Dulse is reported to contain anti-inflammatory and antioxidant compounds, [...] Read more.
Palmaria palmata L. (Palmariaceae), commonly known as “dulse”, is a red alga that grows on the northern coasts of the Atlantic and Pacific oceans, and is widely used as source of fiber and protein. Dulse is reported to contain anti-inflammatory and antioxidant compounds, albeit no study has investigated these effects in primary human neutrophils. Implication strategies to diminish neutrophil activation have the potential to prevent pathological states. We evaluated the ability of a phenolic dulse extract (DULEXT) to modulate the lipopolysaccharide (LPS)-mediated activation of primary human neutrophils. Intracellular reactive oxygen species (ROS) were measured by fluorescence analysis and nitric oxide (NO) production using the Griess reaction. Inflammatory enzymes and cytokines were detected by ELISA and RT-qPCR. The results show that DULEXT diminished the neutrophil activation related to the down-regulation of TLR4 mRNA expression, deceased gene expression and the LPS-induced release of the chemoattractant mediator IL-8 and the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. ROS, NO, and myeloperoxidase (MPO) were also depressed. The data indicated that DULEXT has the potential to disrupt the activation of human primary neutrophils and the derived inflammatory and prooxidant conditions, and suggest a new role for Palmaria palmata L. in the regulation of the pathogenesis of health disorders in which neutrophils play a key role, including atherosclerosis. Full article
(This article belongs to the Special Issue Marine Nutraceuticals and Functional Foods)
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Open AccessReview
Macroalgae as a Valuable Source of Naturally Occurring Bioactive Compounds for the Treatment of Alzheimer’s Disease
Mar. Drugs 2019, 17(11), 609; https://doi.org/10.3390/md17110609 - 25 Oct 2019
Abstract
Alzheimer’s disease (AD) is a neurological condition that affects mostly aged individuals. Evidence suggests that pathological mechanisms involved in the development of AD are associated with cholinergic deficit, glutamate excitotoxicity, beta-amyloid aggregation, tau phosphorylation, neuro-inflammation, and oxidative damage to neurons. Currently there is [...] Read more.
Alzheimer’s disease (AD) is a neurological condition that affects mostly aged individuals. Evidence suggests that pathological mechanisms involved in the development of AD are associated with cholinergic deficit, glutamate excitotoxicity, beta-amyloid aggregation, tau phosphorylation, neuro-inflammation, and oxidative damage to neurons. Currently there is no cure for AD; however, synthetic therapies have been developed to effectively manage some of the symptoms at the early stage of the disease. Natural products from plants and marine organisms have been identified as important sources of bioactive compounds with neuroprotective potentials and less adverse effects compared to synthetic agents. Seaweeds contain several kinds of secondary metabolites such as phlorotannins, carotenoids, sterols, fucoidans, and poly unsaturated fatty acids. However, their neuroprotective effects and mechanisms of action have not been fully explored. This review discusses recent investigations and/or updates on interactions of bioactive compounds from seaweeds with biomarkers involved in the pathogenesis of AD using reports in electronic databases such as Web of science, Scopus, PubMed, Science direct, Scifinder, Taylor and Francis, Wiley, Springer, and Google scholar between 2015 and 2019. Phlorotannins, fucoidans, sterols, and carotenoids showed strong neuroprotective potentials in different experimental models. However, there are no data from human studies and/or clinical trials. Full article
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Open AccessArticle
Effect of Ishophloroglucin A, A Component of Ishige okamurae, on Glucose Homeostasis in the Pancreas and Muscle of High Fat Diet-Fed Mice
Mar. Drugs 2019, 17(11), 608; https://doi.org/10.3390/md17110608 - 25 Oct 2019
Abstract
Ishophloroglucin A (IPA), a component of Ishige okamurae (IO), was previously evaluated to standardize the antidiabetic potency of IO. However, the potential of IPA as a functional food for diabetes prevention has not yet been evaluated. Here, we investigated if 1.35 mg/kg IPA, [...] Read more.
Ishophloroglucin A (IPA), a component of Ishige okamurae (IO), was previously evaluated to standardize the antidiabetic potency of IO. However, the potential of IPA as a functional food for diabetes prevention has not yet been evaluated. Here, we investigated if 1.35 mg/kg IPA, which is the equivalent content of IPA in 75 mg/kg IO, improved glucose homeostasis in high-fat diet (HFD)-induced diabetes after 12 weeks of treatment. IPA significantly ameliorated glucose intolerance, reducing fasting glucose levels as well as 2 h glucose levels in HFD mice. In addition, IPA exerted a protective effect on the pancreatic function in HFD mice via pancreatic β-cells and C-peptide. The level of glucose transporter 4 (GLUT4) in the muscles of HFD mice was stimulated by IPA intake. Our results suggested that IPA, which is a component of IO, can improve glucose homeostasis via GLUT4 in the muscles of HFD mice. IO may be used as a functional food for the prevention of diabetes. Full article
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