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Open AccessArticle

Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia

by Tatyana A. Kuznetsova, Natalya N. Besednova, Larisa M. Somova and Natalya G. Plekhova

Mar. Drugs 2014, 12(2), 886-898; https://doi.org/10.3390/md12020886 - 31 Jan 2014

Cited by 31 | Viewed by 7622

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 [...] 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)

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1112 KiB

Open AccessArticle

Functional Metabolomics Uncovers Metabolic Alterations Associated to Severe Oxidative Stress in MCF7 Breast Cancer Cells Exposed to Ascididemin

by Daniel Morvan

Mar. Drugs 2013, 11(10), 3846-3860; https://doi.org/10.3390/md11103846 - 11 Oct 2013

Cited by 14 | Viewed by 5950

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 and [...] 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)

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503 KiB

Open AccessArticle

Anti-Inflammatory Components of the Starfish Astropecten polyacanthus

by Nguyen Phuong Thao, Nguyen Xuan Cuong, Bui Thi Thuy Luyen, Tran Hong Quang, Tran Thi Hong Hanh, Sohyun Kim, Young-Sang Koh, Nguyen Hoai Nam, Phan Van Kiem, Chau Van Minh and Young Ho Kim

Mar. Drugs 2013, 11(8), 2917-2926; https://doi.org/10.3390/md11082917 - 13 Aug 2013

Cited by 30 | Viewed by 9165

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, we [...] 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)

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506 KiB

Open AccessArticle

Krempfielins J-M, New Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

by Yan-Ning Lee, Chi-Jen Tai, Tsong-Long Hwang and Jyh-Horng Sheu

Mar. Drugs 2013, 11(8), 2741-2750; https://doi.org/10.3390/md11082741 - 02 Aug 2013

Cited by 25 | Viewed by 6256

Abstract

New four eunicellin-based diterpenoids, krempfielins J–M (1–4) 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 [...] Read more.

New four eunicellin-based diterpenoids, krempfielins J–M (1–4) 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 1–6 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)

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Open AccessArticle

Lithothamnion muelleri Controls Inflammatory Responses, Target Organ Injury and Lethality Associated with Graft-versus-Host Disease in Mice

by Barbara M. Rezende, Priscila T. T. Bernardes, Carolina B. Resende, Rosa M. E. Arantes, Danielle G. Souza, Fernão C. Braga, Marina G. M. Castor, Mauro M. Teixeira and Vanessa Pinho

Mar. Drugs 2013, 11(7), 2595-2615; https://doi.org/10.3390/md11072595 - 18 Jul 2013

Cited by 12 | Viewed by 6875

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-versus [...] 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)

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2208 KiB

Open AccessArticle

Oxygenated Polyketides from Plakinastrella mamillaris as a New Chemotype of PXR Agonists

by Carmen Festa, Claudio D'Amore, Barbara Renga, Gianluigi Lauro, Simona De Marino, Maria Valeria D'Auria, Giuseppe Bifulco, Angela Zampella and Stefano Fiorucci

Mar. Drugs 2013, 11(7), 2314-2327; https://doi.org/10.3390/md11072314 - 02 Jul 2013

Cited by 38 | Viewed by 7137

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 extensive [...] 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)

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400 KiB

Open AccessArticle

Perna canaliculus Lipid Complex PCSO-524™ Demonstrated Pain Relief for Osteoarthritis Patients Benchmarked against Fish Oil, a Randomized Trial, without Placebo Control

by Marek Zawadzki, Claudia Janosch and Jacek Szechinski

Mar. Drugs 2013, 11(6), 1920-1935; https://doi.org/10.3390/md11061920 - 05 Jun 2013

Cited by 26 | Viewed by 11910

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, is [...] 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)

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948 KiB

Open AccessArticle

Cytotoxic and Anti-Inflammatory Metabolites from the Soft Coral Scleronephthya gracillimum

by Hui-Yu Fang, Chi-Hsin Hsu, Chih-Hua Chao, Zhi-Hong Wen, Yang-Chang Wu, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2013, 11(6), 1853-1865; https://doi.org/10.3390/md11061853 - 29 May 2013

Cited by 22 | Viewed by 6458

Abstract

Five new pregnane-type steroids, sclerosteroids J–N (1–5), 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. [...] Read more.

Five new pregnane-type steroids, sclerosteroids J–N (1–5), 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)

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Open AccessArticle

Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells

by Ching-Yen Lin, Mei-Chin Lu, Jui-Hsin Su, Ching-Liang Chu, David Shiuan, Ching-Feng Weng, Ping-Jyun Sung and Kao-Jean Huang

Mar. Drugs 2013, 11(4), 1336-1350; https://doi.org/10.3390/md11041336 - 22 Apr 2013

Cited by 27 | Viewed by 6767

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). Here, [...] 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)

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617 KiB

Open AccessArticle

Differential in Gel Electrophoresis (DIGE) Comparative Proteomic Analysis of Macrophages Cell Cultures in Response to Perthamide C Treatment

by Annalisa Vilasi, Maria Chiara Monti, Alessandra Tosco, Simona De Marino, Luigi Margarucci, Raffaele Riccio and Agostino Casapullo

Mar. Drugs 2013, 11(4), 1288-1299; https://doi.org/10.3390/md11041288 - 17 Apr 2013

Cited by 7 | Viewed by 6607

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 important [...] 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)

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978 KiB

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

by Hsin-Pai Lee, Shi-Ying Huang, Yen-You Lin, Hui-Min Wang, Yen-Hsuan Jean, Shu-Fen Wu, Chang-Yih Duh and Zhi-Hong Wen

Mar. Drugs 2013, 11(1), 99-113; https://doi.org/10.3390/md11010099 - 10 Jan 2013

Cited by 30 | Viewed by 8202

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. Lemnalol [...] 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)

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Review

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1175 KiB

Open AccessReview

Anti-Inflammatory Activities of Natural Products Isolated from Soft Corals of Taiwan between 2008 and 2012

by Wen-Chi Wei, Ping-Jyun Sung, Chang-Yih Duh, Bo-Wei Chen, Jyh-Horng Sheu and Ning-Sun Yang

Mar. Drugs 2013, 11(10), 4083-4126; https://doi.org/10.3390/md11104083 - 23 Oct 2013

Cited by 93 | Viewed by 10498

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 information [...] 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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