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15 pages, 5215 KiB

Open AccessArticle

Diphlorethohydroxycarmalol Isolated from Ishige okamurae Represses High Glucose-Induced Angiogenesis In Vitro and In Vivo

by K. H. N. Fernando, Hye-Won Yang, Yunfei Jiang, You-Jin Jeon and BoMi Ryu

Mar. Drugs 2018, 16(10), 375; https://doi.org/10.3390/md16100375 - 10 Oct 2018

Cited by 30 | Viewed by 4084

Abstract

Diabetes mellitus causes abnormalities of angiogenesis leading to vascular dysfunction and serious pathologies. Diphlorethohydroxycarmalol (DPHC), which is isolated from Ishige okamurae, is well known for its bioactivities, including antihyperglycemic and protective functions against diabetes-related pathologies. In the present study, the inhibitory effect [...] Read more.

Diabetes mellitus causes abnormalities of angiogenesis leading to vascular dysfunction and serious pathologies. Diphlorethohydroxycarmalol (DPHC), which is isolated from Ishige okamurae, is well known for its bioactivities, including antihyperglycemic and protective functions against diabetes-related pathologies. In the present study, the inhibitory effect of DPHC on high glucose-induced angiogenesis was investigated on the human vascular endothelial cell line EA.hy926. DPHC inhibited the cell proliferation, cell migration, and tube formation in cells exposed to 30 mM of glucose to induce angiogenesis. Furthermore, the effect of DPHC against high glucose-induced angiogenesis was evaluated in zebrafish embryos. The treatment of embryos with DPHC suppressed high glucose-induced dilation in the retinal vessel diameter and vessel formation. Moreover, DPHC could inhibit high glucose-induced vascular endothelial growth factor receptor 2 (VEGFR-2) expression and its downstream signaling cascade. Overall, these findings suggest that DPHC is actively involved in the suppression of high glucose-induced angiogenesis. Hence, DPHC is a potential agent for the development of therapeutics against angiogenesis induced by diabetes. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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10 pages, 1929 KiB

Open AccessArticle

Anti-Oxidant and Fucoxanthin Contents of Brown Alga Ishimozuku (Sphaerotrichia divaricata) from the West Coast of Aomori, Japan

by Hayato Maeda, Satoru Fukuda, Hikari Izumi and Naotsune Saga

Mar. Drugs 2018, 16(8), 255; https://doi.org/10.3390/md16080255 - 30 Jul 2018

Cited by 45 | Viewed by 4444

Abstract

Fucoxanthin is a specific carotenoid in brown seaweeds with remarkable biological properties. Ishimozuku (Sphaerotrichia divaricata), an edible brown alga from northern Japan, has morphology that is almost identical to that of Okinawa-mozuku (Cladosiphon okamuranus) harvested off Okinawa, Japan. However, [...] Read more.

Fucoxanthin is a specific carotenoid in brown seaweeds with remarkable biological properties. Ishimozuku (Sphaerotrichia divaricata), an edible brown alga from northern Japan, has morphology that is almost identical to that of Okinawa-mozuku (Cladosiphon okamuranus) harvested off Okinawa, Japan. However, because of Ishimozuku’s lower availability compared to Okinawa-mozuku, the contents of its nutrient compounds remain unclear. The present study analyzed fucoxanthin and anti-oxidant compound contents of Ishimozuku harvested off the northern coast of Japan from 2014 to 2016. First, 80% ethanol extract solutions were prepared from Ishimozuku harvested from several west coast areas of Aomori, Japan. Then, polyphenol content was analyzed using the Folin–Ciocalteu method. Then anti-oxidative effects were analyzed by their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and hydrogen peroxide scavenging activity. Furthermore, fucoxanthin contents were measured using high performance liquid chromatography (HPLC) analysis. Fucoxanthin contents of Ishimozuku were 105.6–1148.5 μg/g dry weight. Total polyphenol contents of Ishimozuku were of 0.296–0.958 mg/g dry weight: higher than Okinawa-mozuku (0.082 ± 0.011 mg/g dry weight). The anti-oxidation effects of Ishimozuku accompanied the polyphenol content. These results suggest that Ishimozuku contains various anti-oxidant components and has high potential to provide the promotion of human health. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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13 pages, 1979 KiB

Open AccessArticle

Structural Characteristics and Anticoagulant Property In Vitro and In Vivo of a Seaweed Sulfated Rhamnan

by Xue Liu, Shuyao Wang, Sujian Cao, Xiaoxi He, Ling Qin, Meijia He, Yajing Yang, Jiejie Hao and Wenjun Mao

Mar. Drugs 2018, 16(7), 243; https://doi.org/10.3390/md16070243 - 20 Jul 2018

Cited by 46 | Viewed by 4721

Abstract

Great diversity and metabolite complexity of seaweeds offer a unique and exclusive source of renewable drug molecules. Polysaccharide from seaweed has potential as a promising candidate for marine drug development. In the present study, seaweed polysaccharide (SPm) was isolated from Monostroma angicava, [...] Read more.

Great diversity and metabolite complexity of seaweeds offer a unique and exclusive source of renewable drug molecules. Polysaccharide from seaweed has potential as a promising candidate for marine drug development. In the present study, seaweed polysaccharide (SPm) was isolated from Monostroma angicava, the polymeric repeat units and anticoagulant property in vitro and in vivo of SPm were investigated. SPm was a sulfated polysaccharide which was mainly constituted by 3-linked, 2-linked-α-l-rhamnose residues with partially sulfate groups at C-2 of 3-linked α-l-rhamnose residues and C-3 of 2-linked α-l-rhamnose residues. Small amounts of xylose and glucuronic acid exist in the forms of β-d-Xylp(4SO₄)-(1→ and β-d-GlcA-(1→. SPm effectively prolonged clotting time as evaluated by the activated partial thromboplastin time and thrombin time assays, and exhibited strong anticoagulant activity in vitro and in vivo. The fibrin(ogen)olytic and thrombolytic properties of SPm were evaluated by plasminogen activator inhibitior-1, fibrin degradation products, D-dimer and clot lytic rate assays using rats plasma, and the results showed that SPm possessed high fibrin(ogen)olytic and thrombolytic properties. These results suggested that SPm has potential as a novel anticoagulant agent. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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15 pages, 1862 KiB

Open AccessArticle

Green Alga Ulva spp. Hydrolysates and Their Peptide Fractions Regulate Cytokine Production in Splenic Macrophages and Lymphocytes Involving the TLR4-NFκB/MAPK Pathways

by Raúl E. Cian, Cristina Hernández-Chirlaque, Reyes Gámez-Belmonte, Silvina R. Drago, Fermín Sánchez de Medina and Olga Martínez-Augustin

Mar. Drugs 2018, 16(7), 235; https://doi.org/10.3390/md16070235 - 11 Jul 2018

Cited by 33 | Viewed by 4267

Abstract

Hydrolysates of food protein sources have immunomodulatory effects, which are of interest for use as functional foods. In this study, we have characterized the immune regulatory effect on rat splenocytes, macrophages and T lymphocytes of Ulva spp. hydrolysates and their peptide fractions with [...] Read more.

Hydrolysates of food protein sources have immunomodulatory effects, which are of interest for use as functional foods. In this study, we have characterized the immune regulatory effect on rat splenocytes, macrophages and T lymphocytes of Ulva spp. hydrolysates and their peptide fractions with or without in vitro gastrointestinal digestion and/or ultrafiltration. IL-10 was induced in almost all conditions and cell types obtained from wild type animals. The induction was in general increased by ultrafiltration and in vitro gastrointestinal digestion. TNF was also induced in basal conditions. In turn, TNF and IFN-γ production was attenuated by the hydrolysate products in lipopolysaccharide or concanavalin A immune stimulated cells. Inhibitors for the activation of NFκB, MAPK p38 and JNK inhibited IL-10 induction in rat splenocytes. The response was dramatically attenuated in TLR4^−/− cells, and only modestly in TLR2^−/− cells. Food peptides from Ulva spp. genus exert anti-inflammatory effects in immune cells mediated by TLR4 and NFκB. Similarity with the immunomodulatory profile of protein hydrolysates from other sources suggests a common mechanism. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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14 pages, 1692 KiB

Open AccessArticle

The Effect of Fucoidan from the Brown Alga Fucus evanescence on the Activity of α-N-Acetylgalactosaminidase of Human Colon Carcinoma Cells

by Irina Bakunina, Oksana Chadova, Olesya Malyarenko and Svetlana Ermakova

Mar. Drugs 2018, 16(5), 155; https://doi.org/10.3390/md16050155 - 10 May 2018

Cited by 9 | Viewed by 6154

Abstract

α-N-acetylgalactosaminidase (EC 3.2.1.49) (alpha-NaGalase) catalyzes the hydrolysis of N-acetamido-2-deoxy-α-d-galactoside residues from non-reducing ends of various complex carbohydrates and glycoconjugates. It is known that human cancer cells express an alpha-NaGalase, which accumulates in the blood plasma of patients. The [...] Read more.

α-N-acetylgalactosaminidase (EC 3.2.1.49) (alpha-NaGalase) catalyzes the hydrolysis of N-acetamido-2-deoxy-α-d-galactoside residues from non-reducing ends of various complex carbohydrates and glycoconjugates. It is known that human cancer cells express an alpha-NaGalase, which accumulates in the blood plasma of patients. The enzyme deglycosylates the Gc protein-derived macrophage activating factor (GcMAF) and inhibits macrophage activity acting as an immunosuppressor. The high specific activity 0.033 ± 0.002 μmol mg⁻¹ min⁻¹ of the enzyme was found in human colon carcinoma cells DLD-1. The alpha-NaGalase of DLD-1 cells was isolated and biochemical characterized. The enzyme exhibits maximum activity at pH 5.2 and temperature 55 °C. The K_m is 2.15 mM, V_max–0.021 μmol min⁻¹ mL⁻¹, k_cat–1.55 min⁻¹ and k_cat/K_m–0.72 min⁻¹ mM⁻¹ at 37 °C, pH 5.2. The effects of fucoidan from the brown alga Fucus evanescence on the activity of alpha-NaGalase in human colon carcinoma DLD-1 cells and on the biosynthesis of this enzyme were investigated. It was shown that fucoidan did not inhibit free alpha-NaGalase, however, it reduced the expression of the enzyme in the DLD-1 cells at IC₅₀ 73 ± 4 μg mL⁻¹. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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11 pages, 3194 KiB

Open AccessArticle

Triphlorethol A, a Dietary Polyphenol from Seaweed, Decreases Sleep Latency and Increases Non-Rapid Eye Movement Sleep in Mice

by Minseok Yoon and Suengmok Cho

Mar. Drugs 2018, 16(5), 139; https://doi.org/10.3390/md16050139 - 24 Apr 2018

Cited by 19 | Viewed by 5423

Abstract

In our previous studies, we have demonstrated that marine polyphenol phlorotannins promote sleep through the benzodiazepine site of the gamma-aminobutyric acid type A (GABA_A) receptors. In this follow-up study, the sleep-promoting effects of triphlorethol A, one of the major phlorotannin constituents, [...] Read more.

In our previous studies, we have demonstrated that marine polyphenol phlorotannins promote sleep through the benzodiazepine site of the gamma-aminobutyric acid type A (GABA_A) receptors. In this follow-up study, the sleep-promoting effects of triphlorethol A, one of the major phlorotannin constituents, were investigated. The effect of triphlorethol A on sleep-wake architecture and profiles was evaluated based on electroencephalogram and electromyogram data from C57BL/6N mice and compared with the well-known hypnotic drug zolpidem. Oral administration of triphlorethol A (5, 10, 25, and 50 mg/kg) dose-dependently decreased sleep latency and increased sleep duration during pentobarbital-induced sleep in imprinting control region mice. Triphlorethol A (50 mg/kg) significantly decreased sleep latency and increased the amount of non-rapid eye movement sleep (NREMS) in C57BL/6N mice, without affecting rapid eye movement sleep (REMS). There was no significant difference between the effects of triphlorethol A at 50 mg/kg and zolpidem at 10 mg/kg. Triphlorethol A had no effect on delta activity (0.5–4 Hz) of NREMS, whereas zolpidem significantly decreased it. These results not only support the sleep-promoting effects of marine polyphenol phlorotannins, but also suggest that the marine polyphenol compound triphlorethol A is a promising structure for developing novel sedative hypnotics. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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2700 KiB

Open AccessArticle

3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes

by Ki Cheon Kim, Yu Jae Hyun, Susara Ruwan Kumara Madduma Hewage, Mei Jing Piao, Kyoung Ah Kang, Hee Kyoung Kang, Young Sang Koh, Mee Jung Ahn and Jin Won Hyun

Mar. Drugs 2017, 15(9), 291; https://doi.org/10.3390/md15090291 - 18 Sep 2017

Cited by 18 | Viewed by 4390

Abstract

A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of [...] Read more.

A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of glutathione-related enzymes and the cell survival of human keratinocytes (HaCaT cells) was investigated. BDB treatment increased the protein and mRNA levels of glutathione synthesizing enzymes and enhanced the production of reduced glutathione in HaCaT cells. Furthermore, BDB activated NF-E2-related factor 2 (Nrf2) and promoted its localization into the nucleus by phosphorylating its up-stream signaling proteins, extracellular signal–regulated kinase and protein kinase B. Thus, BDB increased the production of reduced glutathione and established cellular protection against oxidative stress via an Nrf2-mediated pathway. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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Review

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25 pages, 10926 KiB

Open AccessReview

Diterpenes from the Marine Algae of the Genus Dictyota

by Jiayun Chen, Hong Li, Zishuo Zhao, Xue Xia, Bo Li, Jinrong Zhang and Xiaojun Yan

Mar. Drugs 2018, 16(5), 159; https://doi.org/10.3390/md16050159 - 11 May 2018

Cited by 57 | Viewed by 6844

Abstract

Species of the brown algae of the genus Dictyota are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the discovery of diterpenes possessing broad chemical defensive activities from this genus. Most of these diterpenes exhibit [...] Read more.

Species of the brown algae of the genus Dictyota are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the discovery of diterpenes possessing broad chemical defensive activities from this genus. Most of these diterpenes exhibit significant biological activities, such as antiviral, cytotoxic and chemical defensive activities. In the present review, we summarized diterpenes isolated from the brown algae of the genus. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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22 pages, 1229 KiB

Open AccessFeature PaperReview

Seaweed Bioactive Compounds against Pathogens and Microalgae: Potential Uses on Pharmacology and Harmful Algae Bloom Control

by Soukaina El Amrani Zerrifi, Fatima El Khalloufi, Brahim Oudra and Vitor Vasconcelos

Mar. Drugs 2018, 16(2), 55; https://doi.org/10.3390/md16020055 - 09 Feb 2018

Cited by 60 | Viewed by 11572

Abstract

Cyanobacteria are found globally due to their adaptation to various environments. The occurrence of cyanobacterial blooms is not a new phenomenon. The bloom-forming and toxin-producing species have been a persistent nuisance all over the world over the last decades. Evidence suggests that this [...] Read more.

Cyanobacteria are found globally due to their adaptation to various environments. The occurrence of cyanobacterial blooms is not a new phenomenon. The bloom-forming and toxin-producing species have been a persistent nuisance all over the world over the last decades. Evidence suggests that this trend might be attributed to a complex interplay of direct and indirect anthropogenic influences. To control cyanobacterial blooms, various strategies, including physical, chemical, and biological methods have been proposed. Nevertheless, the use of those strategies is usually not effective. The isolation of natural compounds from many aquatic and terrestrial plants and seaweeds has become an alternative approach for controlling harmful algae in aquatic systems. Seaweeds have received attention from scientists because of their bioactive compounds with antibacterial, antifungal, anti-microalgae, and antioxidant properties. The undesirable effects of cyanobacteria proliferations and potential control methods are here reviewed, focusing on the use of potent bioactive compounds, isolated from seaweeds, against microalgae and cyanobacteria growth. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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