Marine Drugs

Editorial

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6 pages, 176 KiB

Open AccessEditorial

Selected Papers from the Third International Symposium on Life Science

by Valentin A. Stonik

Mar. Drugs 2020, 18(2), 117; https://doi.org/10.3390/md18020117 - 18 Feb 2020

Viewed by 2058

Abstract

The search for and isolation of marine biologically active compounds, as well as relevant studies on their structure and properties are important for the adding knowledge about molecular diversity in nature and creation of medicines and other useful products on this basis [...] [...] Read more.

The search for and isolation of marine biologically active compounds, as well as relevant studies on their structure and properties are important for the adding knowledge about molecular diversity in nature and creation of medicines and other useful products on this basis [...] Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

Research

Jump to: Editorial, Review

16 pages, 1533 KiB

Open AccessArticle

Comparative Genomics and CAZyme Genome Repertoires of Marine Zobellia amurskyensis KMM 3526^T and Zobellia laminariae KMM 3676^T

by Nadezhda Chernysheva, Evgeniya Bystritskaya, Anna Stenkova, Ilya Golovkin, Olga Nedashkovskaya and Marina Isaeva

Mar. Drugs 2019, 17(12), 661; https://doi.org/10.3390/md17120661 - 24 Nov 2019

Cited by 23 | Viewed by 4499

Abstract

We obtained two novel draft genomes of type Zobellia strains with estimated genome sizes of 5.14 Mb for Z. amurskyensis KMM 3526^Т and 5.16 Mb for Z. laminariae KMM 3676^Т. Comparative genomic analysis has been carried out between obtained and [...] Read more.

We obtained two novel draft genomes of type Zobellia strains with estimated genome sizes of 5.14 Mb for Z. amurskyensis KMM 3526^Т and 5.16 Mb for Z. laminariae KMM 3676^Т. Comparative genomic analysis has been carried out between obtained and known genomes of Zobellia representatives. The pan-genome of Zobellia genus is composed of 4853 orthologous clusters and the core genome was estimated at 2963 clusters. The genus CAZome was represented by 775 GHs classified into 62 families, 297 GTs of 16 families, 100 PLs of 13 families, 112 CEs of 13 families, 186 CBMs of 18 families and 42 AAs of six families. A closer inspection of the carbohydrate-active enzyme (CAZyme) genomic repertoires revealed members of new putative subfamilies of GH16 and GH117, which can be biotechnologically promising for production of oligosaccharides and rare monomers with different bioactivities. We analyzed AA3s, among them putative FAD-dependent glycoside oxidoreductases (FAD-GOs) being of particular interest as promising biocatalysts for glycoside deglycosylation in food and pharmaceutical industries. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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20 pages, 4376 KiB

Open AccessArticle

A Novel Alkaline Phosphatase/Phosphodiesterase, CamPhoD, from Marine Bacterium Cobetia amphilecti KMM 296

by Yulia Noskova, Galina Likhatskaya, Natalia Terentieva, Oksana Son, Liudmila Tekutyeva and Larissa Balabanova

Mar. Drugs 2019, 17(12), 657; https://doi.org/10.3390/md17120657 - 22 Nov 2019

Cited by 15 | Viewed by 3926

Abstract

A novel extracellular alkaline phosphatase/phosphodiesterase from the structural protein family PhoD that encoded by the genome sequence of the marine bacterium Cobetia amphilecti KMM 296 (CamPhoD) has been expressed in Escherichia coli cells. The calculated molecular weight, the number of amino acids, and [...] Read more.

A novel extracellular alkaline phosphatase/phosphodiesterase from the structural protein family PhoD that encoded by the genome sequence of the marine bacterium Cobetia amphilecti KMM 296 (CamPhoD) has been expressed in Escherichia coli cells. The calculated molecular weight, the number of amino acids, and the isoelectric point (pI) of the mature protein’s subunit are equal to 54832.98 Da, 492, and 5.08, respectively. The salt-tolerant, bimetal-dependent enzyme CamPhoD has a molecular weight of approximately 110 kDa in its native state. CamPhoD is activated by Co²⁺, Mg²⁺, Ca²⁺, or Fe³⁺ at a concentration of 2 mM and exhibits maximum activity in the presence of both Co²⁺ and Fe³⁺ ions in the incubation medium at pH 9.2. The exogenous ions, such as Zn²⁺, Cu²⁺, and Mn²⁺, as well as chelating agents EDTA and EGTA, do not have an appreciable effect on the CamPhoD activity. The temperature optimum for the CamPhoD activity is 45 °C. The enzyme catalyzes the cleavage of phosphate mono- and diester bonds in nucleotides, releasing inorganic phosphorus from p-nitrophenyl phosphate (pNPP) and guanosine 5′-triphosphate (GTP), as determined by the Chen method, with rate approximately 150- and 250-fold higher than those of bis-pNPP and 5′-pNP-TMP, respectively. The Michaelis–Menten constant (K_m), V_max, and efficiency (k_cat/K_m) of CamPhoD were 4.2 mM, 0.203 mM/min, and 7988.6 S⁻¹/mM; and 6.71 mM, 0.023 mM/min, and 1133.0 S⁻¹/mM for pNPP and bis-pNPP as the chromogenic substrates, respectively. Among the 3D structures currently available, in this study we found only the low identical structure of the Bacillus subtilis enzyme as a homologous template for modeling CamPhoD, with a new architecture of the phosphatase active site containing Fe³⁺ and two Ca²⁺ ions. It is evident that the marine bacterial phosphatase/phosphidiesterase CamPhoD is a new structural member of the PhoD family. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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10 pages, 2299 KiB

Open AccessArticle

Echinochrome A Reduces Colitis in Mice and Induces In Vitro Generation of Regulatory Immune Cells

by Su-Jeong Oh, Yoojin Seo, Ji-Su Ahn, Ye Young Shin, Ji Won Yang, Hyoung Kyu Kim, Jin Han, Natalia P. Mishchenko, Sergey A. Fedoreyev, Valentin A. Stonik and Hyung-Sik Kim

Mar. Drugs 2019, 17(11), 622; https://doi.org/10.3390/md17110622 - 31 Oct 2019

Cited by 25 | Viewed by 3924

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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15 pages, 1903 KiB

Open AccessArticle

Magnificamide, a β-Defensin-Like Peptide from the Mucus of the Sea Anemone Heteractis magnifica, Is a Strong Inhibitor of Mammalian α-Amylases

by Oksana Sintsova, Irina Gladkikh, Aleksandr Kalinovskii, Elena Zelepuga, Margarita Monastyrnaya, Natalia Kim, Lyudmila Shevchenko, Steve Peigneur, Jan Tytgat, Emma Kozlovskaya and Elena Leychenko

Mar. Drugs 2019, 17(10), 542; https://doi.org/10.3390/md17100542 - 21 Sep 2019

Cited by 20 | Viewed by 4258

Abstract

Sea anemones’ venom is rich in peptides acting on different biological targets, mainly on cytoplasmic membranes and ion channels. These animals are also a source of pancreatic α-amylase inhibitors, which have the ability to control the glucose level in the blood and can [...] Read more.

Sea anemones’ venom is rich in peptides acting on different biological targets, mainly on cytoplasmic membranes and ion channels. These animals are also a source of pancreatic α-amylase inhibitors, which have the ability to control the glucose level in the blood and can be used for the treatment of prediabetes and type 2 diabetes mellitus. Recently we have isolated and characterized magnificamide (44 aa, 4770 Da), the major α-amylase inhibitor of the sea anemone Heteractis magnifica mucus, which shares 84% sequence identity with helianthamide from Stichodactyla helianthus. Herein, we report some features in the action of a recombinant analog of magnificamide. The recombinant peptide inhibits porcine pancreatic and human saliva α-amylases with Ki’s equal to 0.17 ± 0.06 nM and 7.7 ± 1.5 nM, respectively, and does not show antimicrobial or channel modulating activities. We have concluded that the main function of magnificamide is the inhibition of α-amylases; therefore, its functionally active recombinant analog is a promising agent for further studies as a potential drug candidate for the treatment of the type 2 diabetes mellitus. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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14 pages, 2935 KiB

Open AccessArticle

Echinochrome A Promotes Ex Vivo Expansion of Peripheral Blood-Derived CD34⁺ Cells, Potentially through Downregulation of ROS Production and Activation of the Src-Lyn-p110δ Pathway

by Ga-Bin Park, Min-Jung Kim, Elena A. Vasileva, Natalia P. Mishchenko, Sergey A. Fedoreyev, Valentin A. Stonik, Jin Han, Ho Sup Lee, Daejin Kim and Jee-Yeong Jeong

Mar. Drugs 2019, 17(9), 526; https://doi.org/10.3390/md17090526 - 9 Sep 2019

Cited by 17 | Viewed by 4077

Abstract

Intracellular reactive oxygen species (ROS) play an important role in the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). HSPCs are difficult to be expanded ex vivo while maintaining their stemness when they are exposed to oxidative damage after being released [...] Read more.

Intracellular reactive oxygen species (ROS) play an important role in the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). HSPCs are difficult to be expanded ex vivo while maintaining their stemness when they are exposed to oxidative damage after being released from the bone marrow. There have been efforts to overcome this limitation by using various cytokine cocktails and antioxidants. In this study, we investigated the effects of echinochrome A (Ech A)-a well-established and non-toxic antioxidant-on the ex vivo expansion of HSPCs by analyzing a CD34⁺ cell population and their biological functions. We observed that Ech A-induced suppression of ROS generation and p38-MAPK/JNK phosphorylation causes increased expansion of CD34⁺ cells. Moreover, p38-MAPK/JNK inhibitors SB203580 and SP600125 promoted ex vivo expansion of CD34⁺ cells. We also demonstrated that the activation of Lyn kinase and p110δ is a novel mechanism for Ech A to enhance ex vivo expansion of CD34⁺ cells. Ech A upregulated phospho-Src, phospho-Lyn, and p110δ expression. Furthermore, the Ech A-induced ex vivo expansion of CD34⁺ cells was inhibited by pretreatment with the Src family inhibitor PP1 and p110δ inhibitor CAL-101; PP1 blocked p110δ upregulation and PI3K/Akt activation, whereas CAL-101 and PI3K/Akt pathway inhibitor LY294002 did not block Src/Lyn activation. These results suggest that Ech A initially induces Src/Lyn activation, upregulates p110δ expression, and finally activates the PI3K/Akt pathway. CD34⁺ cells expanded in the presence of Ech A produced equal or more hematopoietic colony-forming cells than unexpanded CD34⁺ cells. In conclusion, Ech A promotes the ex vivo expansion of CD34⁺ cells through Src/Lyn-mediated p110δ expression, suppression of ROS generation, and p38-MAPK/JNK activation. Hence, Ech A is a potential candidate modality for the ex vivo, and possibly in vivo, expansion of CD34⁺ cells. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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8 pages, 1256 KiB

Open AccessArticle

Echinochrome A Attenuates Cerebral Ischemic Injury through Regulation of Cell Survival after Middle Cerebral Artery Occlusion in Rat

by Ran Kim, Daeun Hur, Hyoung Kyu Kim, Jin Han, Natalia P. Mishchenko, Sergey A. Fedoreyev, Valentin A. Stonik and Woochul Chang

Mar. Drugs 2019, 17(9), 501; https://doi.org/10.3390/md17090501 - 28 Aug 2019

Cited by 21 | Viewed by 3131

Abstract

Of late, researchers have taken interest in alternative medicines for the treatment of brain ischemic stroke, where full recovery is rarely seen despite advanced medical technologies. Due to its antioxidant activity, Echinochrome A (Ech A), a natural compound found in sea urchins, has [...] Read more.

Of late, researchers have taken interest in alternative medicines for the treatment of brain ischemic stroke, where full recovery is rarely seen despite advanced medical technologies. Due to its antioxidant activity, Echinochrome A (Ech A), a natural compound found in sea urchins, has acquired attention as an alternative clinical trial source for the treatment of ischemic stroke. The current study demonstrates considerable potential of Ech A as a medication for cerebral ischemic injury. To confirm the effects of Ech A on the recovery of the injured region and behavioral decline, Ech A was administered through the external carotid artery in a rat middle cerebral artery occlusion model after reperfusion. The expression level of cell viability-related factors was also examined to confirm the mechanism of brain physiological restoration. Based on the results obtained, we propose that Ech A ameliorates the physiological deterioration by its antioxidant effect which plays a protective role against cell death, subsequent to post cerebral ischemic stroke. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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14 pages, 1495 KiB

Open AccessArticle

New Trisulfated Steroids from the Vietnamese Marine Sponge Halichondria vansoesti and Their PSA Expression and Glucose Uptake Inhibitory Activities

by Kseniya M. Tabakmakher, Tatyana N. Makarieva, Vladimir A. Denisenko, Roman S. Popov, Pavel S. Dmitrenok, Sergey A. Dyshlovoy, Boris B. Grebnev, Carsten Bokemeyer, Gunhild von Amsberg and Nguyen X. Cuong

Mar. Drugs 2019, 17(8), 445; https://doi.org/10.3390/md17080445 - 27 Jul 2019

Cited by 11 | Viewed by 3430

Abstract

Seven new unusual polysulfated steroids—topsentiasterol sulfate G (1), topsentiasterol sulfate I (2), topsentiasterol sulfate H (3), bromotopsentiasterol sulfate D (4), dichlorotopsentiasterol sulfate D (8), bromochlorotopsentiasterol sulfate D (9), and 4β [...] Read more.

Seven new unusual polysulfated steroids—topsentiasterol sulfate G (1), topsentiasterol sulfate I (2), topsentiasterol sulfate H (3), bromotopsentiasterol sulfate D (4), dichlorotopsentiasterol sulfate D (8), bromochlorotopsentiasterol sulfate D (9), and 4β-hydroxyhalistanol sulfate C (10), as well as three previously described—topsentiasterol sulfate D (7), chlorotopsentiasterol sulfate D (5) and iodotopsentiasterol sulfate D (6) have been isolated from the marine sponge Halichondria vansoesti. Structures of these compounds were determined by detailed analysis of 1D- and 2D-NMR and HRESIMS data, as well as chemical transformations. The effects of the compounds on human prostate cancer cells PC-3 and 22Rv1 were investigated. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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14 pages, 4136 KiB

Open AccessArticle

Gliotoxin Enhances Autophagic Cell Death via the DAPK1-TAp63 Signaling Pathway in Paclitaxel-Resistant Ovarian Cancer Cells

by Ga-Bin Park, Jee-Yeong Jeong and Daejin Kim

Mar. Drugs 2019, 17(7), 412; https://doi.org/10.3390/md17070412 - 12 Jul 2019

Cited by 26 | Viewed by 4179

Abstract

Death-associated protein kinase 1 (DAPK1) expression induced by diverse death stimuli mediates apoptotic activity in various cancers, including ovarian cancer. In addition, mutual interaction between the tumor suppressor p53 and DAPK1 influences survival and death in several cancer cell lines. However, the exact [...] Read more.

Death-associated protein kinase 1 (DAPK1) expression induced by diverse death stimuli mediates apoptotic activity in various cancers, including ovarian cancer. In addition, mutual interaction between the tumor suppressor p53 and DAPK1 influences survival and death in several cancer cell lines. However, the exact role and connection of DAPK1 and p53 family proteins (p53, p63, and p73) in drug-resistant ovarian cancer cells have not been studied previously. In this study, we investigated whether DAPK1 induction by gliotoxin derived from marine fungus regulates the level of transcriptionally active p63 (TAp63) to promote apoptosis in an autophagy-dependent manner. Pre-exposure of paclitaxel-resistant ovarian cancer cells to gliotoxin inhibited the expression of multidrug resistant-associated proteins (MDR1 and MRP1-3), disrupted the mitochondrial membrane potential, and induced caspase-dependent apoptosis through autophagy induction after subsequent treatment with paclitaxel. Gene silencing of DAPK1 prevented TAp63-mediated downregulation of MDR1 and MRP1-3 and autophagic cell death after sequential treatment with gliotoxin and then paclitaxel. However, pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, had no effect on the levels of DAPK1 and TAp63 or on the inhibition of MDR1 and MRP1-3. These results suggest that DAPK1-mediated TAp63 upregulation is one of the critical pathways that induce apoptosis in chemoresistant cancer cells. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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15 pages, 3711 KiB

Open AccessArticle

Therapeutic Cell Protective Role of Histochrome under Oxidative Stress in Human Cardiac Progenitor Cells

by Ji Hye Park, Na-Kyung Lee, Hye Ji Lim, Sinthia Mazumder, Vinoth Kumar Rethineswaran, Yeon-Ju Kim, Woong Bi Jang, Seung Taek Ji, Songhwa Kang, Da Yeon Kim, Le Thi Hong Van, Ly Thanh Truong Giang, Dong Hwan Kim, Jong Seong Ha, Jisoo Yun, Hyungtae Kim, Jin Han, Natalia P. Mishchenko, Sergey A. Fedoreyev, Elena A. Vasileva, Sang Mo Kwon and Sang Hong Baek Show full author list Hide full author list

Mar. Drugs 2019, 17(6), 368; https://doi.org/10.3390/md17060368 - 21 Jun 2019

Cited by 21 | Viewed by 5896

Abstract

Cardiac progenitor cells (CPCs) are resident stem cells present in a small portion of ischemic hearts and function in repairing the damaged heart tissue. Intense oxidative stress impairs cell metabolism thereby decreasing cell viability. Protecting CPCs from undergoing cellular apoptosis during oxidative stress [...] Read more.

Cardiac progenitor cells (CPCs) are resident stem cells present in a small portion of ischemic hearts and function in repairing the damaged heart tissue. Intense oxidative stress impairs cell metabolism thereby decreasing cell viability. Protecting CPCs from undergoing cellular apoptosis during oxidative stress is crucial in optimizing CPC-based therapy. Histochrome (sodium salt of echinochrome A—a common sea urchin pigment) is an antioxidant drug that has been clinically used as a pharmacologic agent for ischemia/reperfusion injury in Russia. However, the mechanistic effect of histochrome on CPCs has never been reported. We investigated the protective effect of histochrome pretreatment on human CPCs (hCPCs) against hydrogen peroxide (H₂O₂)-induced oxidative stress. Annexin V/7-aminoactinomycin D (7-AAD) assay revealed that histochrome-treated CPCs showed significant protective effects against H₂O₂-induced cell death. The anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-xL were significantly upregulated, whereas the pro-apoptotic proteins BCL2-associated X (Bax), H₂O₂-induced cleaved caspase-3, and the DNA damage marker, phosphorylated histone (γH2A.X) foci, were significantly downregulated upon histochrome treatment of hCPCs in vitro. Further, prolonged incubation with histochrome alleviated the replicative cellular senescence of hCPCs. In conclusion, we report the protective effect of histochrome against oxidative stress and present the use of a potent and bio-safe cell priming agent as a potential therapeutic strategy in patient-derived hCPCs to treat heart disease. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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10 pages, 1069 KiB

Open AccessArticle

Marine Bacterium Vibrio sp. CB1-14 Produces Guanidine Alkaloid 6-epi-Monanchorin, Previously Isolated from Marine Polychaete and Sponges

by Tatyana Makarieva, Larisa Shubina, Valeria Kurilenko, Marina Isaeva, Nadezhda Chernysheva, Roman Popov, Evgeniya Bystritskaya, Pavel Dmitrenok and Valentin Stonik

Mar. Drugs 2019, 17(4), 213; https://doi.org/10.3390/md17040213 - 4 Apr 2019

Cited by 5 | Viewed by 3495

Abstract

Twenty-three bacterial strains were isolated from the secreted mucus trapping net of the marine polychaete Chaetopterus variopedatus (phylum Annelida) and twenty strains were identified using 16S rRNA gene analysis. Strain CB1-14 was recognized as a new species of the genus Vibrio using the [...] Read more.

Twenty-three bacterial strains were isolated from the secreted mucus trapping net of the marine polychaete Chaetopterus variopedatus (phylum Annelida) and twenty strains were identified using 16S rRNA gene analysis. Strain CB1-14 was recognized as a new species of the genus Vibrio using the eight-gene multilocus sequence analysis (MLSA) and genome sequences of nineteen type Vibrio strains. This Vibrio sp. was cultured, and 6-epi-monanchorin (2), previously isolated from the polychaete and two sponge species, was found in the cells and culture broth. The presence of the 6-epi-monanchorin was confirmed by its isolation followed by ¹H NMR and HRESIMS analysis. These results showed the microbial origin of the bicyclic guanidine alkaloid 2 in C. variopedatus. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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20 pages, 6096 KiB

Open AccessArticle

Spinochrome D Attenuates Doxorubicin-Induced Cardiomyocyte Death via Improving Glutathione Metabolism and Attenuating Oxidative Stress

by Chang Shin Yoon, Hyoung Kyu Kim, Natalia P. Mishchenko, Elena A. Vasileva, Sergey A. Fedoreyev, Valentin A. Stonik and Jin Han

Mar. Drugs 2019, 17(1), 2; https://doi.org/10.3390/md17010002 - 20 Dec 2018

Cited by 35 | Viewed by 5458

Abstract

Doxorubicin, an anthracycline from Streptomyces peucetius, exhibits antitumor activity against various cancers. However, doxorubicin is cardiotoxic at cumulative doses, causing increases in intracellular reactive oxygen species in the heart. Spinochrome D (SpD) has a structure of 2,3,5,6,8-pentahydroxy-1,4-naphthoquinone and is a structural analogue [...] Read more.

Doxorubicin, an anthracycline from Streptomyces peucetius, exhibits antitumor activity against various cancers. However, doxorubicin is cardiotoxic at cumulative doses, causing increases in intracellular reactive oxygen species in the heart. Spinochrome D (SpD) has a structure of 2,3,5,6,8-pentahydroxy-1,4-naphthoquinone and is a structural analogue of well-known sea urchin pigment echinochrome A. We previously reported that echinochrome A is cardioprotective against doxorubicin toxicity. In the present study, we assessed the cardioprotective effects of SpD against doxorubicin and determined the underlying mechanism. ¹H-NMR-based metabolomics and mass spectrometry-based proteomics were utilized to characterize the metabolites and proteins induced by SpD in a human cardiomyocyte cell line (AC16) and human breast cancer cell line (MCF-7). Multivariate analyses identified 12 discriminating metabolites (variable importance in projection > 1.0) and 1814 proteins from SpD-treated AC16 cells. Proteomics and metabolomics analyses showed that glutathione metabolism was significantly influenced by SpD treatment in AC16 cells. SpD treatment increased ATP production and the oxygen consumption rate in D-galactose-treated AC16 cells. SpD protected AC16 cells from doxorubicin cytotoxicity, but it did not affect the anticancer properties. With SpD treatment, the mitochondrial membrane potential and mitochondrial calcium localization were significantly different between cardiomyocytes and cancer cell lines. Our findings suggest that SpD could be cardioprotective against the cytotoxicity of doxorubicin. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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10 pages, 1435 KiB

Open AccessArticle

Antiviral and Antioxidant Properties of Echinochrome A

by Sergey A. Fedoreyev, Natalia V. Krylova, Natalia P. Mishchenko, Elena A. Vasileva, Evgeny A. Pislyagin, Olga V. Iunikhina, Vyacheslav F. Lavrov, Oksana A. Svitich, Linna K. Ebralidze and Galina N. Leonova

Mar. Drugs 2018, 16(12), 509; https://doi.org/10.3390/md16120509 - 15 Dec 2018

Cited by 67 | Viewed by 6197

Abstract

The aim of this study was to examine the in vitro antioxidant and antiviral activities of echinochrome A and echinochrome-based antioxidant composition against tick-borne encephalitis virus (TBEV) and herpes simplex virus type 1 (HSV-1). The antioxidant composition, which is a mixture of echinochrome [...] Read more.

The aim of this study was to examine the in vitro antioxidant and antiviral activities of echinochrome A and echinochrome-based antioxidant composition against tick-borne encephalitis virus (TBEV) and herpes simplex virus type 1 (HSV-1). The antioxidant composition, which is a mixture of echinochrome A, ascorbic acid, and α-tocopherol (5:5:1), showed higher antioxidant and antiviral effects than echinochrome A. We suppose that echinochrome A and its composition can both directly affect virus particles and indirectly enhance antioxidant defense mechanisms in the hosting cell. The obtained results allow considering the echinochrome A and the composition of antioxidants on its basis as the promising agents with the both antioxidant and antiviral activities. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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10 pages, 2722 KiB

Open AccessArticle

Mutagenesis Studies and Structure-function Relationships for GalNAc/Gal-Specific Lectin from the Sea Mussel Crenomytilus grayanus

by Svetlana N. Kovalchuk, Nina S. Buinovskaya, Galina N. Likhatskaya, Valery A. Rasskazov, Oksana M. Son, Liudmila A. Tekutyeva and Larissa A. Balabanova

Mar. Drugs 2018, 16(12), 471; https://doi.org/10.3390/md16120471 - 27 Nov 2018

Cited by 9 | Viewed by 3481

Abstract

The GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus (CGL) with anticancer activity represents а novel lectin family with β-trefoil fold. Earlier, the crystal structures of CGL complexes with globotriose, galactose and galactosamine, and mutagenesis studies have revealed that the lectin contained three [...] Read more.

The GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus (CGL) with anticancer activity represents а novel lectin family with β-trefoil fold. Earlier, the crystal structures of CGL complexes with globotriose, galactose and galactosamine, and mutagenesis studies have revealed that the lectin contained three carbohydrate-binding sites. The ability of CGL to recognize globotriose (Gb3) on the surface of breast cancer cells and bind mucin-type glycoproteins, which are often associated with oncogenic transformation, makes this compound to be perspective as a biosensor for cancer diagnostics. In this study, we describe results on in silico analysis of binding mechanisms of CGL to ligands (galactose, globotriose and mucin) and evaluate the individual contribution of the amino acid residues from carbohydrate-binding sites to CGL activity by site-directed mutagenesis. The alanine substitutions of His37, His129, Glu75, Asp127, His85, Asn27 and Asn119 affect the CGL mucin-binding activity, indicating their importance in the manifestation of lectin activity. It has been found that CGL affinity to ligands depends on their structure, which is determined by the number of hydrogen bonds in the CGL-ligand complexes. The obtained results should be helpful for understanding molecular machinery of CGL functioning and designing a synthetic analog of CGL with enhanced carbohydrate-binding properties. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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12 pages, 1914 KiB

Open AccessArticle

Oxysterols from a Marine Sponge Inflatella sp. and Their Action in 6-Hydroxydopamine-Induced Cell Model of Parkinson’s Disease

by Sophia A. Kolesnikova, Ekaterina G. Lyakhova, Anatoly I. Kalinovsky, Roman S. Popov, Ekaterina A. Yurchenko and Valentin A. Stonik

Mar. Drugs 2018, 16(11), 458; https://doi.org/10.3390/md16110458 - 21 Nov 2018

Cited by 13 | Viewed by 4025

Abstract

Four new oxysterols 1–4 along with previously known oxygenated sterols 5–14 were isolated from the sponge Inflatella sp., collected from the Sea of Okhotsk. Structures of 1–4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses [...] Read more.

Four new oxysterols 1–4 along with previously known oxygenated sterols 5–14 were isolated from the sponge Inflatella sp., collected from the Sea of Okhotsk. Structures of 1–4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses as well as by comparison of the corresponding experimental data with those reported in literature. The influence of compounds 1–14 on the viability of neuronal Neuro2a cells treated by 6-hydroxydopamine and reactive oxygen species (ROS) formation in these cells was investigated. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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15 pages, 1793 KiB

Open AccessArticle

Neuroprotective Activity of Some Marine Fungal Metabolites in the 6-Hydroxydopamin- and Paraquat-Induced Parkinson’s Disease Models

by Ekaterina A. Yurchenko, Ekaterina S. Menchinskaya, Evgeny A. Pislyagin, Phan Thi Hoai Trinh, Elena V. Ivanets, Olga F. Smetanina and Anton N. Yurchenko

Mar. Drugs 2018, 16(11), 457; https://doi.org/10.3390/md16110457 - 21 Nov 2018

Cited by 31 | Viewed by 5399

Abstract

A new melatonin analogue 6-hydroxy-N-acetyl-β-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid [...] Read more.

A new melatonin analogue 6-hydroxy-N-acetyl-β-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid (2) and 8-methoxy-3,5-dimethylisochroman-6-ol (3) from Penicillium sp. KMM 4672, candidusin A (4) and 4″-dehydroxycandidusin A (5) from Aspergillus sp. KMM 4676, and diketopiperazine mactanamide (6) from Aspergillus flocculosus, were investigated in the 6-hydroxydopamine (6-OHDA)- and paraquat (PQ)-induced Parkinson’s disease (PD) cell models. All of them protected Neuro2a cells against the damaging influence of 6-OHDA to varying degrees. This effect may be realized via a reactive oxygen species (ROS) scavenging pathway. The new melatonin analogue more effectively protected Neuro2A cells against the 6-OHDA-induced neuronal death, in comparison with melatonin, as well as against the PQ-induced neurotoxicity. Dehydroxylation at C-3″ and C-4″ significantly increased free radical scavenging and neuroprotective activity of candidusin-related p-terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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13 pages, 2604 KiB

Open AccessArticle

Effects of Carrageenans on Biological Properties of Echinochrome

by Ekaterina V. Sokolova, Natalia I. Menzorova, Victoria N. Davydova, Alexandra S. Kuz’mich, Anna O. Kravchenko, Natalya P. Mishchenko and Irina M. Yermak

Mar. Drugs 2018, 16(11), 419; https://doi.org/10.3390/md16110419 - 1 Nov 2018

Cited by 8 | Viewed by 3098

Abstract

Sea urchin pigment echinochrome A (Ech), a water-insoluble compound, is the active substance in the cardioprotective and antioxidant drug Histochrome^® (PIBOC FEB RAS, Moscow, Russia). It has been established that Ech dissolves in aqueous solutions of carrageenans (CRGs). Herein, we describe the [...] Read more.

Sea urchin pigment echinochrome A (Ech), a water-insoluble compound, is the active substance in the cardioprotective and antioxidant drug Histochrome^® (PIBOC FEB RAS, Moscow, Russia). It has been established that Ech dissolves in aqueous solutions of carrageenans (CRGs). Herein, we describe the effects of different types of CRGs on some properties of Ech. Our results showed that CRGs significantly decreased the spermotoxicity of Ech, against the sea urchin S. intermedius sperm. Ech, as well as its complex with CRG, did not affect the division and development of early embryos of the sea urchin. Ech reduced reactive oxygen species production (ROS) in neutrophils, caused by CRG. The obtained complexes of these substances with pro- and anti-activating ROS formation properties illustrate the possibility of modulating the ROS induction, using these compounds. The CRGs stimulate the induction of anti-inflammatory IL-10 synthesis, whereas Ech inhibits this synthesis and increases the production of the pro-inflammatory cytokines IL-6 and TNFα. The inclusion of Ech, in the complex with the CRGs, decreases Ech’s ability to induce the expression of pro-inflammatory cytokines, especially TNFα, and increases the induction of anti-inflammatory cytokine IL-10. Thus, CRGs modify the action of Ech, by decreasing its pro-inflammatory effect. Whereas, the Ech’s protective action towards human epithelial HT-29 cells remains to be unaltered in the complex, with κ/β-CRG, under stress conditions. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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Review

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21 pages, 1023 KiB

Open AccessReview

Metabolites of Seaweeds as Potential Agents for the Prevention and Therapy of Influenza Infection

by Natalia Besednova, Tatiana Zaporozhets, Tatiana Kuznetsova, Ilona Makarenkova, Lydmila Fedyanina, Sergey Kryzhanovsky, Olesya Malyarenko and Svetlana Ermakova

Mar. Drugs 2019, 17(6), 373; https://doi.org/10.3390/md17060373 - 22 Jun 2019

Cited by 29 | Viewed by 6105

Abstract

Context: Seaweed metabolites (fucoidans, carrageenans, ulvans, lectins, and polyphenols) are biologically active compounds that target proteins or genes of the influenza virus and host components that are necessary for replication and reproduction of the virus. Objective: This review gathers the information available in [...] Read more.

Context: Seaweed metabolites (fucoidans, carrageenans, ulvans, lectins, and polyphenols) are biologically active compounds that target proteins or genes of the influenza virus and host components that are necessary for replication and reproduction of the virus. Objective: This review gathers the information available in the literature regarding to the useful properties of seaweeds metabolites as potential agents for the prevention and therapy of influenza infection. Materials and methods: The sources of scientific literature were found in various electronic databases (i.e., PubMed, Web of Science, and ScienceDirect) and library search. The retrospective search depth is 25 years. Results: Influenza is a serious medical and social problem for humanity. Recently developed drugs are quite effective against currently circulating influenza virus strains, but their use can lead to the selection of resistant viral strains. In this regard, new therapeutic approaches and drugs with a broad spectrum of activity are needed. Metabolites of seaweeds fulfill these requirements. This review presents the results of in vitro and in vivo experimental and clinical studies about the effectiveness of these compounds in combating influenza infection and explains the necessity of their use as a potential basis for the creation of new drugs with a broad spectrum of activity. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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