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Special Issue "Marine Compounds and Inflammation"

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

Deadline for manuscript submissions: closed (30 April 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Agostino Casapullo

Department of Pharmaceutical and Biomedical Sciences, University of Salerno, via Ponte don Melillo, 84084 Fisciano, Italy
Fax: +39 089 969602
Interests: marine natural products; structure elucidation; chemical proteomics; target discovery; bioorganic chemistry

Special Issue Information

Dear Collegues,

Oceans cover about 70% of the earth’s surface and marine organisms comprise approximately a half of the total biodiversity. Marine natural products possess a unique chemical diversity and have evolved for optimal interactions with biological macromolecules, constituting an enormous library of novel compounds with wide biological properties useful in the drug discovery process.

The search for new drugs is currently moving toward a rationalization in which chemistry and pharmacology are joined into a targeted approach to drug discovery, focused on specific diseases and molecular targets. In this context, inflammation is increasingly considered a crucial biological pathway, due to its involvement in a large number of diseases such as allergies, asthma, rheumatoid arthritis, inflammatory bowel diseases, atherosclerosis, and in particular in the initiation and progression cancer, strictly implicated in many inflammatory processes such as increased angiogenesis and DNA synthesis, genomic damage, cellular proliferation, disruption of DNA repair pathways, and inhibition of apoptosis. On this basis, the exploration of marine sources in search of novel chemical scaffolds for the treatment of inflammatory-driven diseases represents a key pharmacological goal.

As the Guest Editor, I would like to invite scientists to report their findings in the field of marine anti-inflammatory compounds.

Prof. Dr. Agostino Casapullo
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

  • marine natural products
  • inflammation
  • transcription factors
  • cytokines
  • chemokines
  • drug discovery
  • anti-inflammatory effects
  • bioactive compounds
  • marine pharmaceuticals
  • cancer
  • autoimmune diseases
  • intracellular signaling pathways

Published Papers (12 papers)

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Research

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Open AccessArticle Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia
Mar. Drugs 2014, 12(2), 886-898; doi:10.3390/md12020886
Received: 7 November 2013 / Revised: 24 January 2014 / Accepted: 26 January 2014 / Published: 31 January 2014
Cited by 6 | PDF Full-text (1645 KB) | HTML Full-text | XML Full-text
Abstract
An important problem of treating patients with endotoxemia is to find drugs to reduce the negative effects of endotoxin on the organism. We tested fucoidan (sulfated polysaccharide) from the brown alga Fucus evanescens as a potential drug in a mouse model of [...] Read more.
An important problem of treating patients with endotoxemia is to find drugs to reduce the negative effects of endotoxin on the organism. We tested fucoidan (sulfated polysaccharide) from the brown alga Fucus evanescens as a potential drug in a mouse model of endotoxemia inducted by lipopolysaccharide (LPS). The survival time of mice injected with LPS increased under fucoidan treatment compared with the group of mice injected with LPS only. The preventive administration of fucoidan to mice with endotoxemia resulted in inhibition of increased levels of proinflammatory cytokines (TNFα and IL-6), as well as decreasing of the processes of hypercoagulability. The parenteral or per os administration of fucoidan resulted in decreasing the degree of microcirculatory disorders and secondary dystrophic-destructive changes in parenchymal organs of mice with endotoxemia. Taken together, these results demonstrate that fucoidan prevents endotoxin-induced damage in a mouse model of endotoxemia and increases the mice’s resistance to LPS. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Open AccessArticle Functional Metabolomics Uncovers Metabolic Alterations Associated to Severe Oxidative Stress in MCF7 Breast Cancer Cells Exposed to Ascididemin
Mar. Drugs 2013, 11(10), 3846-3860; doi:10.3390/md11103846
Received: 18 July 2013 / Revised: 26 August 2013 / Accepted: 29 August 2013 / Published: 11 October 2013
Cited by 4 | PDF Full-text (1112 KB) | HTML Full-text | XML Full-text
Abstract
Marine natural products are a source of promising agents for cancer treatment. However, there is a need to improve the evaluation of their mechanism of action in tumors. Metabolomics of the response to anti-tumor agents is a tool to reveal candidate biomarkers [...] Read more.
Marine natural products are a source of promising agents for cancer treatment. However, there is a need to improve the evaluation of their mechanism of action in tumors. Metabolomics of the response to anti-tumor agents is a tool to reveal candidate biomarkers and metabolic targets. We used two-dimensional high-resolution magic angle spinning proton-NMR spectroscopy-based metabolomics to investigate the response of MCF7 breast cancer cells to ascididemin, a marine alkaloid and lead molecule for anti-cancer treatment. Ascididemin induced severe oxidative stress and apoptosis within 48 h of exposure. Thirty-three metabolites were quantified. Metabolic response involved downregulation of glycolysis and the tricarboxylic acid cycle, and phospholipid metabolism alterations. Candidate metabolic biomarkers of the response of breast cancer cells to ascididemin were proposed including citrate, gluconate, polyunsaturated fatty acids, glycerophospho-choline and -ethanolamine. In addition, candidate metabolic targets were identified. Overall, the response to Asc could be related to severe oxidative stress and anti-inflammatory effects. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Open AccessArticle Anti-Inflammatory Components of the Starfish Astropecten polyacanthus
Mar. Drugs 2013, 11(8), 2917-2926; doi:10.3390/md11082917
Received: 20 June 2013 / Revised: 17 July 2013 / Accepted: 19 July 2013 / Published: 13 August 2013
Cited by 12 | PDF Full-text (503 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, [...] Read more.
Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 μM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 μM) and 6 (IC50 = 79.05 ± 2.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 μM) and 4 (IC50 = 16.73 ± 0.25 μM) moderately inhibited the production of TNF-α and IL-6, respectively. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Figures

Open AccessArticle Krempfielins J-M, New Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi
Mar. Drugs 2013, 11(8), 2741-2750; doi:10.3390/md11082741
Received: 17 June 2013 / Revised: 9 July 2013 / Accepted: 11 July 2013 / Published: 2 August 2013
Cited by 15 | PDF Full-text (506 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New four eunicellin-based diterpenoids, krempfielins J–M (14) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis. The structure [...] Read more.
New four eunicellin-based diterpenoids, krempfielins J–M (14) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis. The structure of compound 2 is rare due to the presence of the highly oxygenated pattern. Anti-inflammatory activity of 16 to inhibit the superoxide anion generation and elastase release in FMLP/CB-induced human neutrophils was also evaluated, and 2 and 4 were shown to possess the ability to inhibit the elastase release. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Open AccessArticle Lithothamnion muelleri Controls Inflammatory Responses, Target Organ Injury and Lethality Associated with Graft-versus-Host Disease in Mice
Mar. Drugs 2013, 11(7), 2595-2615; doi:10.3390/md11072595
Received: 3 May 2013 / Revised: 1 July 2013 / Accepted: 2 July 2013 / Published: 18 July 2013
Cited by 5 | PDF Full-text (954 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of a group of algae with anti-inflammatory, antitumor, and immunomodulatory properties. The present study evaluated the effects of treatment with Lithothamnion muelleri extract (LM) in a model of acute graft- [...] Read more.
Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of a group of algae with anti-inflammatory, antitumor, and immunomodulatory properties. The present study evaluated the effects of treatment with Lithothamnion muelleri extract (LM) in a model of acute graft-versus-host disease (GVHD), using a model of adoptive splenocyte transfer from C57BL/6 donors into B6D2F1 recipient mice. Mice treated with LM showed reduced clinical signs of disease and mortality when compared with untreated mice. LM-treated mice had reduced tissue injury, less bacterial translocation, and decreased levels of proinflammatory cytokines and chemokines (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5)). The polysaccharide-rich fraction derived from LM could inhibit leukocyte rolling and adhesion in intestinal venules, as assessed by intravital microscopy. LM treatment did not impair the beneficial effects of graft-versus-leukaemia (GVL). Altogether, our studies suggest that treatment with Lithothamnion muelleri has a potential therapeutic application in GVHD treatment. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Figures

Open AccessArticle Oxygenated Polyketides from Plakinastrella mamillaris as a New Chemotype of PXR Agonists
Mar. Drugs 2013, 11(7), 2314-2327; doi:10.3390/md11072314
Received: 24 April 2013 / Revised: 27 May 2013 / Accepted: 28 May 2013 / Published: 2 July 2013
Cited by 17 | PDF Full-text (2208 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Further purification of the apolar extracts of the sponge Plakinastrella mamillaris, afforded a new oxygenated polyketide named gracilioether K, together with the previously isolated gracilioethers E–G and gracilioethers I and J. The structure of the new compound has been elucidated by [...] Read more.
Further purification of the apolar extracts of the sponge Plakinastrella mamillaris, afforded a new oxygenated polyketide named gracilioether K, together with the previously isolated gracilioethers E–G and gracilioethers I and J. The structure of the new compound has been elucidated by extensive NMR (1H and 13C, COSY, HSQC, HMBC, and ROESY) and ESI-MS analysis. With the exception of gracilioether F, all compounds are endowed with potent pregnane-X-receptor (PXR) agonistic activity and therefore represent a new chemotype of potential anti-inflammatory leads. Docking calculations suggested theoretical binding modes of the identified compounds, compatible with an agonistic activity on hPXR, and clarified the molecular basis of their biological activities. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Figures

Open AccessArticle Perna canaliculus Lipid Complex PCSO-524™ Demonstrated Pain Relief for Osteoarthritis Patients Benchmarked against Fish Oil, a Randomized Trial, without Placebo Control
Mar. Drugs 2013, 11(6), 1920-1935; doi:10.3390/md11061920
Received: 20 March 2013 / Revised: 8 May 2013 / Accepted: 21 May 2013 / Published: 5 June 2013
Cited by 4 | PDF Full-text (400 KB) | HTML Full-text | XML Full-text
Abstract
Osteoarthritis (OA) typically generates pain, reduced mobility and reduced quality of life. Most conventional treatments for osteoarthritis, such as non-steroidal anti-inflammatory drugs (NSAIDs) and simple analgesics, have side effects. PCSO-524™, a non polar lipid extract from the New Zealand Green Lipped Mussel, [...] Read more.
Osteoarthritis (OA) typically generates pain, reduced mobility and reduced quality of life. Most conventional treatments for osteoarthritis, such as non-steroidal anti-inflammatory drugs (NSAIDs) and simple analgesics, have side effects. PCSO-524™, a non polar lipid extract from the New Zealand Green Lipped Mussel, is rich in omega-3 fatty acids and has been shown to reduce inflammation in both animal studies and patient trials. This OA trial examined pain relief changes in relation to quality of life and safety of use for OA patients who took PCSO-524™ compared with patients who took fish oil (containing an industry standard EPA-18% and DHA-12% blend). PCSO-524™ patients showed a statistically significant improvement compared with patients who took fish oil. There was an 89% decrease in their pain symptoms and 91% reported an improved quality of life. Patients treated with fish oil showed significantly less improvement and a greater level of physical discomfort during the study. These results suggest that PCSO-524™ might offer a potential alternative complementary therapy with no side effects for OA patients. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Open AccessArticle Cytotoxic and Anti-Inflammatory Metabolites from the Soft Coral Scleronephthya gracillimum
Mar. Drugs 2013, 11(6), 1853-1865; doi:10.3390/md11061853
Received: 20 March 2013 / Revised: 19 April 2013 / Accepted: 10 May 2013 / Published: 29 May 2013
Cited by 6 | PDF Full-text (948 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new pregnane-type steroids, sclerosteroids J–N (15), and a diterpenoid with a new chemotype 3-methyl-5-(10′-acetoxy-2′,6′,10′-trimethylundecyl)-2-penten-5-olide (6), have been isolated from a soft coral Scleronephthya gracillimum. The structures of the metabolites were determined by extensive spectroscopic [...] Read more.
Five new pregnane-type steroids, sclerosteroids J–N (15), and a diterpenoid with a new chemotype 3-methyl-5-(10′-acetoxy-2′,6′,10′-trimethylundecyl)-2-penten-5-olide (6), have been isolated from a soft coral Scleronephthya gracillimum. The structures of the metabolites were determined by extensive spectroscopic analysis. Compound 4 exhibited cytotoxicity against HepG2, A549, and MDA-MB-231 cancer cell lines. Furthermore, steroids 2 and 4 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein, and 1, 2, 4 and 5 could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Open AccessArticle Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells
Mar. Drugs 2013, 11(4), 1336-1350; doi:10.3390/md11041336
Received: 26 February 2013 / Revised: 22 March 2013 / Accepted: 27 March 2013 / Published: 22 April 2013
Cited by 7 | PDF Full-text (382 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dendritic cells (DCs) are antigen presenting cells, which can present antigens to T-cells and play an important role in linking innate and adaptive immunity. DC maturation can be induced by many stimuli, including pro-inflammatory cytokines and bacterial products, such as lipopolysaccharides (LPS). [...] Read more.
Dendritic cells (DCs) are antigen presenting cells, which can present antigens to T-cells and play an important role in linking innate and adaptive immunity. DC maturation can be induced by many stimuli, including pro-inflammatory cytokines and bacterial products, such as lipopolysaccharides (LPS). Here, we examined the immunomodulatory effects of marine cembrane compounds, (9E,13E)-5-acetoxy-6-hydroxy-9,13-dimethyl-3- methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (1), (9E,13E)- 5-acetoxy-6-acetyl-9,13-dimethyl-3-methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (2), lobocrassin B (3), (−)14-deoxycrassin (4), cembranolide B (5) and 13-acetoxysarcocrassolide (6) isolated from a soft coral, Lobophytum crassum, on mouse bone marrow-derived dendritic cells (BMDCs). The results revealed that cembrane-type diterpenoids, especially lobocrassin B, effectively inhibited LPS-induced BMDC activation by inhibiting the production of TNF-α. Pre-treatment of BMDCs with Lobocrassin B for 1 h is essential to prohibit the following activation induced by various toll-like receptor (TLR) agonists, such as LPS, zymosan, lipoteichoic acid (LTA) and Pam2CSK4. Inhibition of NF-κB nuclear translocation by lobocrassin B, which is a key transcription factor for cytokine production in TLR signaling, was evident as assayed by high-content image analysis. Lobocrassin B attenuated DC maturation and endocytosis as the expression levels of MHC class II and the co-stimulatory molecules were downregulated, which may affect the function of DCs to initiate the T-cell responses. Thus, lobocrassin B may have the potential in treatment of immune dysregulated diseases in the future. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Open AccessArticle Differential in Gel Electrophoresis (DIGE) Comparative Proteomic Analysis of Macrophages Cell Cultures in Response to Perthamide C Treatment
Mar. Drugs 2013, 11(4), 1288-1299; doi:10.3390/md11041288
Received: 28 February 2013 / Revised: 19 March 2013 / Accepted: 1 April 2013 / Published: 17 April 2013
Cited by 4 | PDF Full-text (617 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Secondary metabolites contained in marine organisms disclose diverse pharmacological activities, due to their intrinsic ability to recognize bio-macromolecules, which alter their expression and modulate their function. Thus, the identification of the cellular pathways affected by marine natural products is crucial to provide [...] Read more.
Secondary metabolites contained in marine organisms disclose diverse pharmacological activities, due to their intrinsic ability to recognize bio-macromolecules, which alter their expression and modulate their function. Thus, the identification of the cellular pathways affected by marine natural products is crucial to provide important functional information concerning their mechanism of action at the molecular level. Perthamide C, a marine sponge metabolite isolated from the polar extracts of Theonella swinhoei and endowed with a broad and interesting anti-inflammatory profile, was found in a previous study to specifically interact with heat shock protein-90 and glucose regulated protein-94, also disclosing the ability to reduce cisplatin-mediated apoptosis. In this paper, we evaluated the effect of this compound on the whole proteome of murine macrophages cells by two-dimensional DIGE proteomics. Thirty-three spots were found to be altered in expression by at least 1.6-fold and 29 proteins were identified by LC ESI-Q/TOF-MS. These proteins are involved in different processes, such as metabolism, structural stability, protein folding assistance and gene expression. Among them, perthamide C modulates the expression of several chaperones implicated in the folding of proteins correlated to apoptosis, such as Hsp90 and T-complexes, and in this context our data shed more light on the cellular effects and pathways altered by this marine cyclo-peptide. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)
Figures

Open AccessArticle Soft Coral-Derived Lemnalol Alleviates Monosodium Urate-Induced Gouty Arthritis in Rats by Inhibiting Leukocyte Infiltration and iNOS, COX-2 and c-Fos Protein Expression
Mar. Drugs 2013, 11(1), 99-113; doi:10.3390/md11010099
Received: 28 November 2012 / Revised: 21 December 2012 / Accepted: 26 December 2012 / Published: 10 January 2013
Cited by 8 | PDF Full-text (978 KB) | HTML Full-text | XML Full-text
Abstract
An acute gout attack manifests in the joint as dramatic inflammation. To date, the clinical use of medicinal agents has typically led to undesirable side effects. Numerous efforts have failed to create an effective and safe agent for the treatment of gout. [...] Read more.
An acute gout attack manifests in the joint as dramatic inflammation. To date, the clinical use of medicinal agents has typically led to undesirable side effects. Numerous efforts have failed to create an effective and safe agent for the treatment of gout. Lemnalol — an extract from Formosan soft coral — has documented anti-inflammatory and anti-nociceptive properties. In the present study, we attempt to examine the therapeutic effects of lemnalol on intra-articular monosodium urate (MSU)-induced gouty arthritis in rats. In the present study, we found that treatment with lemnalol (intramuscular [im]), but not colchicine (oral [po]), significantly attenuated MUS-induced mechanical allodynia, paw edema and knee swelling. Histomorphometric and immunohistochemistry analysis revealed that MSU-induced inflammatory cell infiltration, as well as the elevated expression of c-Fos and pro-inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2) observed in synovial tissue, were significantly inhibited by treatment with lemnalol. We conclude that lemnalol may be a promising candidate for the development of a new treatment for gout and other acute neutrophil-driven inflammatory diseases. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)

Review

Jump to: Research

Open AccessReview Anti-Inflammatory Activities of Natural Products Isolated from Soft Corals of Taiwan between 2008 and 2012
Mar. Drugs 2013, 11(10), 4083-4126; doi:10.3390/md11104083
Received: 30 July 2013 / Revised: 12 September 2013 / Accepted: 13 September 2013 / Published: 23 October 2013
Cited by 24 | PDF Full-text (1175 KB) | HTML Full-text | XML Full-text
Abstract
This review reports details on the natural products isolated from Taiwan soft corals during the period 2008–2012 focusing on their in vitro and/or in vivo anti-inflammatory activities. Chemical structures, names, and literature references are also reported. This review provides useful and specific [...] Read more.
This review reports details on the natural products isolated from Taiwan soft corals during the period 2008–2012 focusing on their in vitro and/or in vivo anti-inflammatory activities. Chemical structures, names, and literature references are also reported. This review provides useful and specific information on potent anti-inflammatory marine metabolites for future development of immune-modulatory therapeutics. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation)

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