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Marine Natural Products Modulating the Immune System

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

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 33947

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Special Issue Editor

Prof. Dr. Christos Tsatsanis

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Guest Editor

Medical School, University of Crete, Heraklion 70013, Greece
Interests: immunomodulation; inflammation; macrophages; marine natural products

Special Issue Information

Dear Colleagues,

Marine organisms have been a source for bioactive compounds and several drugs that are currently in wide use. Traditional medicine throughout the globe, spanning from the Mediterranean to the Red Sea, Gulf of Bengal, South China Sea, and more, has used extracts from marine organisms as therapeutic remedies. The availability of novel analytical methods, as well as the acknowledgement that marine organisms can provide not only therapeutic but also nutritional resources, has boosted research in the field. A major use of marine organisms and marine organism extracts is the modulating of immune responses, to suppress inflammation, boost anti-tumor immune responses, or affect metabolism and therefore immune-mediated diseases. Our understanding of the contribution of the immune system in the development of diseases has grown, and the impact of marine organism-derived extracts or marine organisms themselves as nutritional supplements on these mechanisms is currently being elucidated. The aim of this Special Issue is to promote research in the field and highlight the importance of marine organisms in health as modulators of the immune system. Work describing the selective action of compounds isolated from marine organisms on the therapy of immune-related diseases or as nutritional supplements supporting health will also be included in this Special Issue.

Prof. Dr. Christos Tsatsanis
Guest Editor

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Keywords

immunity
cancer
inflammation
cardiovascular disease
marine products
algae
fish side streams
nutrition
macrophages
T cells
neutrophils

Published Papers (10 papers)

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Research

17 pages, 1954 KiB

Open AccessArticle

A Novel Pseudoalteromonas xiamenensis Marine Isolate as a Potential Probiotic: Anti-Inflammatory and Innate Immune Modulatory Effects against Thermal and Pathogenic Stresses

by Withanage Prasadini Wasana, Amal Senevirathne, Chamilani Nikapitiya, Tae-Yang Eom, Youngdeuk Lee, Jong-Soo Lee, Do-Hyung Kang, Chulhong Oh and Mahanama De Zoysa

Mar. Drugs 2021, 19(12), 707; https://0-doi-org.brum.beds.ac.uk/10.3390/md19120707 - 15 Dec 2021

Cited by 7 | Viewed by 3043

Abstract

A marine bacterial strain was isolated from seawater and characterized for it beneficial probiotic effects using zebrafish as a model system. The strain was identified by morphological, physiological, biochemical, and phylogenetic analyses. The strain was most closely related to Pseudoalteromonas xiamenensis Y2, with 99.66% similarity; thus, we named it Pseudoalteromonas xiamenensis S1131. Improvement of host disease tolerance for the P. xiamenensis isolate was adapted in a zebrafish model using Edwardsiella piscicida challenge. The larvae were pre-exposed to P. xiamenensis prior to E. piscicida challenge, resulting in a 73.3% survival rate compared to a 46.6% survival for the control. The treated larvae tolerated elevated temperatures at 38 °C, with 85% survival, compared to 60% survival for the control. Assessment of immunomodulatory responses at the mRNA level demonstrated the suppression of pro-inflammatory markers tnfα and il6, and upregulation of heat shock protein hsp90 and mucin genes. The same effect was corroborated by immunoblot analysis, revealing significant inhibition of Tnfα and an enhanced expression of the Hsp90 protein. The antibacterial activity of P. xiamenensis may be related to mucin overexpression, which can suppress bacterial biofilm formation and enhance macrophage uptake. This phenomenon was evaluated using nonstimulated macrophage RAW264.7 cells. Further studies may be warranted to elucidate a complete profile of the probiotic effects, to expand the potential applications of the present P. xiamenensis isolate. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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18 pages, 2257 KiB

Open AccessArticle

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

by Shimaa M. Abou-Zeid, Samira H. Aljuaydi, Huda O. AbuBakr, Enas A. Tahoun, Alessandro Di Cerbo, Mahmoud Alagawany, Samah R. Khalil and Mayada R. Farag

Mar. Drugs 2021, 19(9), 525; https://0-doi-org.brum.beds.ac.uk/10.3390/md19090525 - 18 Sep 2021

Cited by 16 | Viewed by 2999

Abstract

Thiacloprid (TCP) is a widely used neonicotinoid insecticide with a probable toxic hazard to animals and human beings. This hazard has intensified the demand for natural compounds to alleviate the expected toxic insults. This study aimed at determining whether astaxanthin (ASX) could mitigate the hepatotoxic effect of TCP and diminish its suppressive effect on immune responses in rats. Animals received TCP by gavage at 62.1 mg/kg (1/10th LD₅₀) with or without ASX at 40 mg/kg for 60 days. Intoxicated rats showed modulation of serum transaminases and protein profiles. The hemagglutination antibody titer to sheep red blood cells (SRBC) and the number of plaque-forming cells in the spleen were reduced. The cell-mediated immunity and phagocytosis were suppressed, while serum interleukins IL-1β, IL-6, and IL-10 were elevated. Additionally, malondialdehyde, nitric oxide, and 8-hydroxy-2′-deoxyguanosine levels were increased in the liver, spleen, and thymus, with depletion of glutathione and suppression of superoxide dismutase and catalase activities. The expressions of inducible nitric oxide synthase and the high mobility group box protein 1 genes were upregulated with histomorphological alterations in the aforementioned organs. Cotreatment with ASX markedly ameliorated the toxic effects of TCP, and all markers showed a regression trend towards control values. Collectively, our data suggest that the protective effects of ASX on the liver and immune system of TCP-treated animals depend upon improving the antioxidant status and relieving the inflammatory response, and thus it may be used as a promising therapeutic agent to provide superior hepato- and immunoprotection. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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14 pages, 3098 KiB

Open AccessArticle

Collagen-Containing Fish Sidestream-Derived Protein Hydrolysates Support Skin Repair via Chemokine Induction

by Ioanna Lapi, Ourania Kolliniati, Tone Aspevik, Eleftherios E. Deiktakis, Konstantinos Axarlis, Maria G. Daskalaki, Eirini Dermitzaki, Maria Tzardi, Sotirios C. Kampranis, Zouhir El Marsni, Katerina C. Kousoulaki, Christos Tsatsanis and Maria Venihaki

Mar. Drugs 2021, 19(7), 396; https://0-doi-org.brum.beds.ac.uk/10.3390/md19070396 - 15 Jul 2021

Cited by 6 | Viewed by 3382

Abstract

Restoring homeostasis following tissue damage requires a dynamic and tightly orchestrated sequence of molecular and cellular events that ensure repair and healing. It is well established that nutrition directly affects skin homeostasis, while malnutrition causes impaired tissue healing. In this study, we utilized fish sidestream-derived protein hydrolysates including fish collagen as dietary supplements, and investigated their effect on the skin repair process using a murine model of cutaneous wound healing. We explored potential differences in wound closure and histological morphology between diet groups, and analyzed the expression and production of factors that participate in different stages of the repair process. Dietary supplementation with fish sidestream-derived collagen alone (Collagen), or in combination with a protein hydrolysate derived from salmon heads (HSH), resulted in accelerated healing. Chemical analysis of the tested extracts revealed that Collagen had the highest protein content and that HSH contained the great amount of zinc, known to support immune responses. Indeed, tissues from mice fed with collagen-containing supplements exhibited an increase in the expression levels of chemokines, important for the recruitment of immune cells into the damaged wound region. Moreover, expression of a potent angiogenic factor, vascular endothelial growth factor-A (VEGF-A), was elevated followed by enhanced collagen deposition. Our findings suggest that a 5%-supplemented diet with marine collagen-enriched supplements promotes tissue repair in the model of cutaneous wound healing, proposing a novel health-promoting use of fish sidestreams. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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13 pages, 3410 KiB

Open AccessArticle

Attenuating Effects of Dieckol on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Decreasing the NLRP3 Inflammasome and Pyroptosis

by Seyeon Oh, Myeongjoo Son, Kyung-A Byun, Ji Tae Jang, Chang Hu Choi, Kuk Hui Son and Kyunghee Byun

Mar. Drugs 2021, 19(6), 318; https://0-doi-org.brum.beds.ac.uk/10.3390/md19060318 - 30 May 2021

Cited by 21 | Viewed by 4015

Abstract

Nonalcoholic fatty liver disease (NAFLD), which promotes serious health problems, is related to the increase in the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis by a high-fat diet (HFD). Whether dieckol (DK), a component of Ecklonia cava extracts (ECE), attenuated NAFLD in an HFD-induced NAFLD animal model was evaluated. The expression of high mobility group box 1/Toll-like receptor 4/nuclear factor-κB, which initiated the NLRP3 inflammasome, was increased in the liver of HFD-fed animals and significantly decreased with ECE or DK administration. The expression of NLRP3/ASC/caspase-1, which are components of the NLRP3 inflammasome, and the number of pyroptotic cells were increased by HFD and decreased with ECE or DK administration. The accumulation of triglycerides and free fatty acids in the liver was increased by HFD and decreased with ECE or DK administration. The histological NAFLD score was increased by HFD and decreased with ECE or DK administration. The expression of lipogenic genes (FASN, SREBP-2, PPARγ, and FABP4) increased and that of lipolytic genes (PPARα, CPT1A, ATGL, and HSL) was decreased by HFD and attenuated with ECE or DK administration. In conclusion, ECE or DK attenuated NAFLD by decreasing the NLRP3 inflammasome and pyroptosis. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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16 pages, 4154 KiB

Open AccessArticle

Fish Sidestream-Derived Protein Hydrolysates Suppress DSS-Induced Colitis by Modulating Intestinal Inflammation in Mice

by Maria G. Daskalaki, Konstantinos Axarlis, Tone Aspevik, Michail Orfanakis, Ourania Kolliniati, Ioanna Lapi, Maria Tzardi, Eirini Dermitzaki, Maria Venihaki, Katerina Kousoulaki and Christos Tsatsanis

Mar. Drugs 2021, 19(6), 312; https://0-doi-org.brum.beds.ac.uk/10.3390/md19060312 - 28 May 2021

Cited by 10 | Viewed by 4430

Abstract

Inflammatory bowel disease is characterized by extensive intestinal inflammation, and therapies against the disease target suppression of the inflammatory cascade. Nutrition has been closely linked to the development and suppression of inflammatory bowel disease, which to a large extent is attributed to the complex immunomodulatory properties of nutrients. Diets containing fish have been suggested to promote health and suppress inflammatory diseases. Even though most of the health-promoting properties of fish-derived nutrients are attributed to fish oil, the potential health-promoting properties of fish protein have not been investigated. Fish sidestreams contain large amounts of proteins, currently unexploited, with potential anti-inflammatory properties, and may possess additional benefits through bioactive peptides and free amino acids. In this project, we utilized fish protein hydrolysates, based on mackerel and salmon heads and backbones, as well as flounder skin collagen. Mice fed with a diet supplemented with different fish sidestream-derived protein hydrolysates (5% w/w) were exposed to the model of DSS-induced colitis. The results show that dietary supplements containing protein hydrolysates from salmon heads suppressed chemically-induced colitis development as determined by colon length and pro-inflammatory cytokine production. To evaluate colitis severity, we measured the expression of different pro-inflammatory cytokines and chemokines and found that the same supplement suppressed the pro-inflammatory cytokines IL-6 and TNFα and the chemokines Cxcl1 and Ccl3. We also assessed the levels of the anti-inflammatory cytokines IL-10 and Tgfb and found that selected protein hydrolysates induced their expression. Our findings demonstrate that protein hydrolysates derived from fish sidestreams possess anti-inflammatory properties in the model of DSS-induced colitis, providing a novel underexplored source of health-promoting dietary supplements. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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14 pages, 3310 KiB

Open AccessArticle

Diet Supplementation with Fish-Derived Extracts Suppresses Diabetes and Modulates Intestinal Microbiome in a Murine Model of Diet-Induced Obesity

by Konstantinos Axarlis, Maria G. Daskalaki, Sofia Michailidou, Nikolais Androulaki, Antiopi Tsoureki, Evangelia Mouchtaropoulou, Ourania Kolliniati, Ioanna Lapi, Eirini Dermitzaki, Maria Venihaki, Katerina Kousoulaki, Anagnostis Argiriou, Zouhir El Marsni and Christos Tsatsanis

Mar. Drugs 2021, 19(5), 268; https://0-doi-org.brum.beds.ac.uk/10.3390/md19050268 - 11 May 2021

Cited by 4 | Viewed by 4240

Abstract

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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16 pages, 2865 KiB

Open AccessArticle

The Marine Natural Product Furospinulosin 1 Induces Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cell Spheroids, But Not in Cells Grown Traditionally with Longer Treatment

by Esther A. Guzmán, Tara P. Pitts, Priscilla L. Winder and Amy E. Wright

Mar. Drugs 2021, 19(5), 249; https://0-doi-org.brum.beds.ac.uk/10.3390/md19050249 - 28 Apr 2021

Cited by 6 | Viewed by 2693

Abstract

Cancer cells grown in spheroid conditions interact with each other and the extracellular matrix, providing a better representation of the in vivo environment than two-dimensional cultures and are a more clinically relevant model. A discrete screening of genetically diverse marine samples in the spheroid assay led to the identification of a novel activity for the known compound furospinulosin 1. This compound shows activity against MDA-MB-231 triple negative breast cancer cells grown as spheroids and treated for 24 or 48 h. No cytotoxicity was seen in traditional two-dimensional adherent cultures treated for a longer time (72 h). A reverse phase protein array (RPPA) confirmed the limited activity of the compound in cells grown traditionally and revealed changes in protein expression when cells are grown as spheroids that are associated with better clinical prognosis. Analysis of the RPPA data through the Broad institute’s connectivity map suggested the hypothesis that furospinulosin 1 functions as an MEK inhibitor. Analysis of the RPPA data through STRING supports the apoptosis observed. The selectivity exhibited by furospinulosin 1 for triple negative breast cancer cells only when grown as spheroids makes it an interesting compound with strong therapeutic potential that merits further study. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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13 pages, 18950 KiB

Open AccessArticle

Antitumor Effects of a Sesquiterpene Derivative from Marine Sponge in Human Breast Cancer Cells

by Li-Yuan Bai, Jui-Hsin Su, Chang-Fang Chiu, Wei-Yu Lin, Jing-Lan Hu, Chia-Hsien Feng, Chih-Wen Shu and Jing-Ru Weng

Mar. Drugs 2021, 19(5), 244; https://0-doi-org.brum.beds.ac.uk/10.3390/md19050244 - 26 Apr 2021

Cited by 12 | Viewed by 2347

Abstract

In this study, the anti-proliferative effect of ilimaquinone, a sesquiterpene derivative from the marine sponge, in breast cancer cells was investigated. Ilimaquinone inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC₅₀ values of 10.6 μM and 13.5 μM, respectively. Non-tumorigenic human breast epithelial cells were less sensitive to ilimaquinone than breast cancer cells. Flow cytometric and Western blot analysis showed that ilimaquinone induced S-phase arrest by modulating the expression of p-CDC-2 and p21. Ilimaquinone induces apoptosis, which is accompanied by multiple biological biomarkers, including the downregulation of Akt, ERK, and Bax, upregulation of p38, loss of mitochondrial membrane potential, increased reactive oxygen species generation, and induced autophagy. Collectively, these findings suggest that ilimaquinone causes cell cycle arrest as well as induces apoptosis and autophagy in breast cancer cells. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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13 pages, 3471 KiB

Open AccessArticle

Estrogenic Effects of Extracts and Isolated Compounds from Belowground and Aerial Parts of Spartina anglica

by Sullim Lee, Geum Jin Kim, Hyukbean Kwon, Joo-Won Nam, Ji Yun Baek, Sang Hee Shim, Hyukjae Choi and Ki Sung Kang

Mar. Drugs 2021, 19(4), 210; https://0-doi-org.brum.beds.ac.uk/10.3390/md19040210 - 11 Apr 2021

Cited by 6 | Viewed by 2857

Abstract

Menopause, caused by decreases in estrogen production, results in symptoms such as facial flushing, vaginal atrophy, and osteoporosis. Although hormone replacement therapy is utilized to treat menopausal symptoms, it is associated with a risk of breast cancer development. We aimed to evaluate the estrogenic activities of Spartina anglica (SA) and its compounds and identify potential candidates for the treatment of estrogen reduction without the risk of breast cancer. We evaluated the estrogenic and anti-proliferative effects of extracts of SA and its compounds in MCF-7 breast cancer cells. We performed an uterotrophic assay using an immature female rat model. Among extracts of SA, belowground part (SA-bg-E50) had potent estrogenic activity. In the immature female rat model, the administration of SA-bg-E50 increased uterine weight compared with that in the normal group. Among the compounds isolated from SA, 1,3-di-O-trans-feruloyl-(-)-quinic acid (1) had significant estrogenic activity and induced phosphorylation at serine residues of estrogen receptor (ER)α. All extracts and compounds from SA did not increase MCF-7 cell proliferation. Compound 1 is expected to act as an ERα ligand and have estrogenic effects, without side effects, such as breast cancer development. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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14 pages, 2994 KiB

Open AccessFeature PaperArticle

Disulfides from the Brown Alga Dictyopteris membranacea Suppress M1 Macrophage Activation by Inducing AKT and Suppressing MAPK/ERK Signaling Pathways

by Maria G. Daskalaki, Paraskevi Bafiti, Stefanos Kikionis, Maria Laskou, Vassilios Roussis, Efstathia Ioannou, Sotirios C. Kampranis and Christos Tsatsanis

Mar. Drugs 2020, 18(11), 527; https://0-doi-org.brum.beds.ac.uk/10.3390/md18110527 - 24 Oct 2020

Cited by 7 | Viewed by 2561

Abstract

Inflammation is part of the organism’s response to deleterious stimuli, such as pathogens, damaged cells, or irritants. Macrophages orchestrate the inflammatory response obtaining different activation phenotypes broadly defined as M1 (pro-inflammatory) or M2 (homeostatic) phenotypes, which contribute to pathogen elimination or disease pathogenesis. The type and magnitude of the response of macrophages are shaped by endogenous and exogenous factors and can be affected by nutrients or therapeutic agents. Multiple studies have shown that natural products possess immunomodulatory properties and that marine algae contain products with such action. We have previously shown that disulfides isolated from Dictyopteris membranacea suppress nitric oxide (NO) production from activated macrophages, suggesting potential anti-inflammatory actions. In this study, we investigated the anti-inflammatory mechanism of action of bis(5-methylthio-3-oxo-undecyl) disulfide (1), 5-methylthio-1-(3-oxo-undecyl) disulfanylundecan-3-one (2) and 3-hexyl-4,5-dithiocycloheptanone (3). Our results showed that all three compounds inhibited M1 activation of macrophages by down regulating the production of pro-inflammatory cytokines TNFα, IL-6 and IL-12, suppressed the expression of the NO converting enzyme iNOS, and enhanced expression of the M2 activation markers Arginase1 and MRC1. Moreover, disulfides 1 and 2 suppressed the expression of glucose transporters GLUT1 and GLUT3, suggesting that compounds 1 and 2 may affect cell metabolism. We showed that this was due to AKT/MAPK/ERK signaling pathway modulation and specifically by elevated AKT phosphorylation and MAPK/ERK signal transduction reduction. Hence, disulfides 1–3 can be considered as potent candidates for the development of novel anti-inflammatory molecules with homeostatic properties. Full article

(This article belongs to the Special Issue Marine Natural Products Modulating the Immune System)

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