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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 October 2019) | Viewed by 62976

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Prof. Dr. Immacolata Castellano

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Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
Interests: discovery of marine sulfur-containing histidine activities; evolution of natural products biosynthesis; anti-oxidant activities; enzyme target characterization; molecular mechanisms underpinning the response and adaptation of organisms to the marine environment
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Dear Colleagues,

The extraordinary beauty of marine landscapes reflects the vast richness in oceans biodiversity, which is the result of millions of years of evolution and adaptation of marine life to changing environments. The marine environment is indeed a rich source of structurally-diverse, biologically-active compounds with unique potentials. This is also due to the physicochemical nature of marine environments, where conditions of high salinity, pressures, low and high temperatures, and lack of light may lead to the biosynthesis of highly-functionalized and unusual molecules in marine organisms.

Antioxidant compounds play a key role in maintaining cellular redox homeostasis and in the survival of marine organisms constantly exposed to environmental stressors and changes. A great number of molecules produced from seaweeds, microalgae, sponges, corals, tunicates and other marine organisms are known for relieving oxidative stress associated diseases, photo- and skin aging. Marine carotenoids for example are known to have beneficial physiological functions as anti-inflammatory and cardio-protective agents. However, the most exciting marine bioactive molecules potentials remain largely unexplored.

In this Special Issue, researchers are invited to provide recent results and innovative research on different aspects related to the evolution of emergent marine antioxidants biosynthesis, the functional and ecological role in the ocean, the biotechnological production, and the potential applications of these molecules as new drugs, dietary supplements and health care products.

Dr. Immacolata Castellano
Guest Editor

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Keywords

antioxidants
marine natural products
biosynthesis
enzyme evolution
marine drugs
dietary supplements
anti-aging

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Published Papers (9 papers)

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Research

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13 pages, 2147 KiB

Open AccessArticle

Probing the Interactions of Sulfur-Containing Histidine Compounds with Human Gamma-Glutamyl Transpeptidase

by Alfonsina Milito, Mariarita Brancaccio, Michael Lisurek, Mariorosario Masullo, Anna Palumbo and Immacolata Castellano

Mar. Drugs 2019, 17(12), 650; https://doi.org/10.3390/md17120650 - 20 Nov 2019

Cited by 15 | Viewed by 3836

Abstract

Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme involved in glutathione metabolism and maintenance of redox homeostasis. High expression of GGT on tumor cells is associated with an increase of cell proliferation and resistance against chemotherapy. GGT inhibitors that have been evaluated in clinical trials are too toxic for human use. We have previously identified ovothiols, 5(Nπ)-methyl-thiohistidines of marine origin, as non-competitive-like inhibitors of GGT that are more potent than the known GGT inhibitor, 6-diazo-5-oxo-l-norleucine (DON), and are not toxic for human embryonic cells. We extended these studies to the desmethylated form of ovothiol, 5-thiohistidine, and confirmed that this ovothiol derivative also acts as a non-competitive-like GGT inhibitor, with a potency comparable to ovothiol. We also found that both 5-thiohistidine derivatives act as reversible GGT inhibitors compared to the irreversible DON. Finally, we probed the interactions of 5-thiohistidines with GGT by docking analysis and compared them with the 2-thiohistidine ergothioneine, the physiological substrate glutathione, and the DON inhibitor. Overall, our results provide new insight for further development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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14 pages, 1530 KiB

Open AccessArticle

Anti-Aging Effect of Agar Oligosaccharide on Male Drosophila melanogaster and Its Preliminary Mechanism

by Chao Ma, Kun Yang, Yifan Wang and Xianjun Dai

Mar. Drugs 2019, 17(11), 632; https://doi.org/10.3390/md17110632 - 6 Nov 2019

Cited by 26 | Viewed by 4539

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. 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)

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16 pages, 3507 KiB

Open AccessArticle

Purification and Characterization of Antioxidant Peptides Derived from Protein Hydrolysate of the Marine Bivalve Mollusk Tergillarca granosa

by Xiu-Rong Yang, Yi-Ting Qiu, Yu-Qin Zhao, Chang-Feng Chi and Bin Wang

Mar. Drugs 2019, 17(5), 251; https://doi.org/10.3390/md17050251 - 27 Apr 2019

Cited by 63 | Viewed by 5370

Abstract

In this report, protein hydrolysate (TGH) of blood cockle (Tegillarca granosa) was prepared using a two-enzyme system (Alcalase treatment for 1.5 h following Neutrase treatment for 1.5 h). Subsequently, six antioxidant peptides were isolated from TGH using ultrafiltration and chromatography methods, and their amino acid sequences were identified as EPLSD, WLDPDG, MDLFTE, WPPD, EPVV, and CYIE with molecular weights of 559.55, 701.69, 754.81, 513.50, 442.48, and 526.57 Da, respectively. In which, MDLFTE and WPPD exhibited strong scavenging activities on DPPH radical (EC₅₀ values of 0.53 ± 0.02 and 0.36 ± 0.02 mg/mL, respectively), hydroxy radical (EC₅₀ values of 0.47 ± 0.03 and 0.38 ± 0.04 mg/mL, respectively), superoxide anion radical (EC₅₀ values of 0.75 ± 0.04 and 0.46 ± 0.05 mg/mL, respectively), and ABTS cation radical (EC₅₀ values of 0.96 ± 0.08 and 0.54 ± 0.03 mg/mL, respectively). Moreover, MDLFTE and WPPD showed high inhibiting ability on lipid peroxidation. However, MDLFTE and WPPD were unstable and could not retain strong antioxidant activity at high temperatures (>80 °C for 0.5 h), basic pH conditions (pH > 9 for 2.5 h), or during simulated GI digestion. In addition, the effect of simulated gastrointestinal digestion on TGP4 was significantly weaker than that on MDLFTE. Therefore, MDLFTE and WPPD may be more suitable for serving as nutraceutical candidates in isolated forms than as food ingredient candidates in functional foods and products. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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16 pages, 3615 KiB

Open AccessArticle

Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes

by Cheol Park, Hee-Jae Cha, Su Hyun Hong, Gi-Young Kim, Suhkmann Kim, Heui-Soo Kim, Byung Woo Kim, You-Jin Jeon and Yung Hyun Choi

Mar. Drugs 2019, 17(4), 225; https://doi.org/10.3390/md17040225 - 13 Apr 2019

Cited by 63 | Viewed by 7105

Abstract

Phloroglucinol (PG) is a component of phlorotannins, which are abundant in marine brown alga species. Recent studies have shown that PG is beneficial in protecting cells from oxidative stress. In this study, we evaluated the protective efficacy of PG in HaCaT human skin keratinocytes stimulated with oxidative stress (hydrogen peroxide, H₂O₂). The results showed that PG significantly inhibited the H₂O₂-induced growth inhibition in HaCaT cells, which was associated with increased expression of heme oxygenase-1 (HO-1) by the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PG remarkably reversed H₂O₂-induced excessive ROS production, DNA damage, and apoptosis. Additionally, H₂O₂-induced mitochondrial dysfunction was related to a decrease in ATP levels, and in the presence of PG, these changes were significantly impaired. Furthermore, the increases of cytosolic release of cytochrome c and ratio of Bax to Bcl-2, and the activation of caspase-9 and caspase-3 by the H₂O₂ were markedly abolished under the condition of PG pretreatment. However, the inhibition of HO-1 function using zinc protoporphyrin, a HO-1 inhibitor, markedly attenuated these protective effects of PG against H₂O₂. Overall, our results suggest that PG is able to protect HaCaT keratinocytes against oxidative stress-induced DNA damage and apoptosis through activating the Nrf2/HO-1 signaling pathway. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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13 pages, 4182 KiB

Open AccessArticle

Cold-Adapted Glutathione S-Transferases from Antarctic Psychrophilic Bacterium Halomonas sp. ANT108: Heterologous Expression, Characterization, and Oxidative Resistance

by Yanhua Hou, Chenhui Qiao, Yifan Wang, Yatong Wang, Xiulian Ren, Qifeng Wei and Quanfu Wang

Mar. Drugs 2019, 17(3), 147; https://doi.org/10.3390/md17030147 - 1 Mar 2019

Cited by 20 | Viewed by 3554

Abstract

Glutathione S-transferases are one of the most important antioxidant enzymes to protect against oxidative damage induced by reactive oxygen species. In this study, a novel gst gene, designated as hsgst, was derived from Antarctic sea ice bacterium Halomonas sp. ANT108 and expressed in Escherichia coli (E. coli) BL21. The hsgst gene was 603 bp in length and encoded a protein of 200 amino acids. Compared with the mesophilic EcGST, homology modeling indicated HsGST had some structural characteristics of cold-adapted enzymes, such as higher frequency of glycine residues, lower frequency of proline and arginine residues, and reduced electrostatic interactions, which might be in relation to the high catalytic efficiency at low temperature. The recombinant HsGST (rHsGST) was purified to apparent homogeneity with Ni-affinity chromatography and its biochemical properties were investigated. The specific activity of the purified rHsGST was 254.20 nmol/min/mg. The optimum temperature and pH of enzyme were 25 °C and 7.5, respectively. Most importantly, rHsGST retained 41.67% of its maximal activity at 0 °C. 2.0 M NaCl and 0.2% H₂O₂ had no effect on the enzyme activity. Moreover, rHsGST exhibited its protective effects against oxidative stresses in E. coli cells. Due to its high catalytic efficiency and oxidative resistance at low temperature, rHsGST may be a potential candidate as antioxidant in low temperature health foods. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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11 pages, 1949 KiB

Open AccessArticle

Effect of Fermented Fish Oil on Fine Particulate Matter-Induced Skin Aging

by Yu Jae Hyun, Mei Jing Piao, Kyoung Ah Kang, Ao Xuan Zhen, Pincha Devage Sameera Madushan Fernando, Hee Kyoung Kang, Yong Seok Ahn and Jin Won Hyun

Mar. Drugs 2019, 17(1), 61; https://doi.org/10.3390/md17010061 - 18 Jan 2019

Cited by 32 | Viewed by 6594

Abstract

Skin is exposed to various harmful environmental factors such as air pollution, which includes different types of particulate matter (PM). Atmospheric PM has harmful effects on humans through increasing the generation of reactive oxygen species (ROS), which have been reported to promote skin aging via the induction of matrix metalloproteinases (MMPs), which in turn can cause the degradation of collagen. In this study, we investigated the effect of fermented fish oil (FFO) derived from mackerel on fine PM (particles with a diameter < 2.5 µm: PM_2.5)-induced skin aging in human keratinocytes. We found that FFO inhibited the PM_2.5-induced generation of intracellular ROS and MMPs, including MMP-1, MMP-2, and MMP-9. In addition, FFO significantly abrogated the elevation of intracellular Ca²⁺ levels in PM_2.5-treated cells and was also found to block the PM_2.5-induced mitogen-activated protein kinase/activator protein 1 (MAPK/AP-1) pathway. In conclusion, FFO has an anti-aging effect on PM_2.5-induced aging in human keratinocytes. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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13 pages, 2681 KiB

Open AccessArticle

Meroterpenoid-Rich Fraction of the Ethanolic Extract from Sargassum serratifolium Suppressed Oxidative Stress Induced by Tert-Butyl Hydroperoxide in HepG2 Cells

by Sujin Lim, Misung Kwon, Eun-Ji Joung, Taisun Shin, Chul-Woong Oh, Jae Sue Choi and Hyeung-Rak Kim

Mar. Drugs 2018, 16(10), 374; https://doi.org/10.3390/md16100374 - 9 Oct 2018

Cited by 18 | Viewed by 3740

Abstract

Sargassum species have been reported to be a source of phytochemicals, with a wide range of biological activities. In this study, we evaluated the hepatoprotective effect of a meroterpenoid-rich fraction of the ethanolic extract from Sargassum serratifolium (MES) against tert-butyl hydroperoxide (t-BHP)-treated HepG2 cells. Treatment with MES recovered the cell viability from the t-BHP-induced oxidative damage in a dose-dependent manner. It suppressed the reactive oxygen species production, lipid peroxidation, and glutathione depletion in the t-BHP-treated HepG2 cells. The activity of the antioxidants induced by t-BHP, including superoxide dismutase (SOD) and catalase, was reduced by the MES treatment. Moreover, it increased the nuclear translocation of nuclear factor erythroid 2-related factor 2, leading to the enhanced activity of glutathione S transferase, and the increased production of heme oxygenase-1 and NAD(P)H:quinine oxidoreductase 1 in t-BHP-treated HepG2 cells. These results demonstrate that the antioxidant activity of MES substituted the activity of the SOD and catalase, and induced the production of detoxifying enzymes, indicating that MES might be used as a hepatoprotectant against t-BHP-induced oxidative stress. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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Review

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38 pages, 1266 KiB

Open AccessReview

Marine Bacteria versus Microalgae: Who Is the Best for Biotechnological Production of Bioactive Compounds with Antioxidant Properties and Other Biological Applications?

by Masoud Hamidi, Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, Guillaume Pierre, Philippe Michaud and Cédric Delattre

Mar. Drugs 2020, 18(1), 28; https://doi.org/10.3390/md18010028 - 29 Dec 2019

Cited by 67 | Viewed by 8677

Abstract

Natural bioactive compounds with antioxidant activity play remarkable roles in the prevention of reactive oxygen species (ROS) formation. ROS, which are formed by different pathways, have various pathological influences such as DNA damage, carcinogenesis, and cellular degeneration. Incremental demands have prompted the search for newer and alternative resources of natural bioactive compounds with antioxidant properties. The marine environment encompasses almost three-quarters of our planet and is home to many eukaryotic and prokaryotic microorganisms. Because of extreme physical and chemical conditions, the marine environment is a rich source of chemical and biological diversity, and marine microorganisms have high potential as a source of commercially interesting compounds with various pharmaceutical, nutraceutical, and cosmeceutical applications. Bacteria and microalgae are the most important producers of valuable molecules including antioxidant enzymes (such as superoxide dismutase and catalase) and antioxidant substances (such as carotenoids, exopolysaccharides, and bioactive peptides) with various valuable biological properties and applications. Here, we review the current knowledge of these bioactive compounds while highlighting their antioxidant properties, production yield, health-related benefits, and potential applications in various biological and industrial fields. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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21 pages, 3244 KiB

Open AccessReview

Microalgal Carotenoids: A Review of Production, Current Markets, Regulations, and Future Direction

by Lucie Novoveská, Michael E. Ross, Michele S. Stanley, Rémi Pradelles, Virginie Wasiolek and Jean-François Sassi

Mar. Drugs 2019, 17(11), 640; https://doi.org/10.3390/md17110640 - 13 Nov 2019

Cited by 312 | Viewed by 18122

Abstract

Microalgae produce a variety of compounds that are beneficial to human and animal health. Among these compounds are carotenoids, which are microalgal pigments with unique antioxidant and coloring properties. The objective of this review is to evaluate the potential of using microalgae as a commercial feedstock for carotenoid production. While microalgae can produce some of the highest concentrations of carotenoids (especially astaxanthin) in living organisms, there are challenges associated with the mass production of microalgae and downstream processing of carotenoids. This review discusses the synthesis of carotenoids within microalgae, their physiological role, large-scale cultivation of microalgae, up- and down-stream processing, commercial applications, natural versus synthetic carotenoids, and opportunities and challenges facing the carotenoid markets. We emphasize legal aspects and regulatory challenges associated with the commercial production of microalgae-based carotenoids for food/feed, nutraceutical and cosmetic industry in Europe, the USA, the People’s Republic of China, and Japan. This review provides tools and a broad overview of the regulatory processes of carotenoid production from microalgae and other novel feedstocks. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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