Marine Drugs

13 pages, 2993 KiB

Open AccessArticle

Protective Effects of Astaxanthin against Oxidative Stress: Attenuation of TNF-α-Induced Oxidative Damage in SW480 Cells and Azoxymethane/Dextran Sulfate Sodium-Induced Colitis-Associated Cancer in C57BL/6 Mice

by Haifeng Zhang, Min Wang, Yu Zhou, Shaojie Bao, Feng Wang and Chunmei Li

Mar. Drugs 2024, 22(10), 469; https://doi.org/10.3390/md22100469 (registering DOI) - 12 Oct 2024

Abstract

Abstract: In this study, we investigated the protective effects of astaxanthin (AST) against oxidative stress induced by the combination of azoxymethane (AOM) and dextran sulfate sodium (DSS) in colitis-associated cancer (CAC) and TNF-α-induced human colorectal cancer cells (SW480), as well as the underlying [...] Read more.

Abstract: In this study, we investigated the protective effects of astaxanthin (AST) against oxidative stress induced by the combination of azoxymethane (AOM) and dextran sulfate sodium (DSS) in colitis-associated cancer (CAC) and TNF-α-induced human colorectal cancer cells (SW480), as well as the underlying mechanism. In vitro experiments revealed that astaxanthin reduced reactive oxygen species (ROS) generation and inhibited the expression of Phosphorylated JNK (P-JNK), Phosphorylated ERK (P-ERK), Phosphorylated p65 (P-p65), and the NF-κB downstream protein cyclooxygenase-2 (COX-2). In vivo experiments showed that astaxanthin ameliorated AOM/DSS-induced weight loss, shortened the colon length, and caused histomorphological changes. In addition, astaxanthin suppressed cellular inflammation by modulating the MAPK and NF-κB pathways and inhibiting the expression of the proinflammatory cytokines IL-6, IL-1β, and TNF-α. In conclusion, astaxanthin attenuates cellular inflammation and CAC through its antioxidant effects. Full article

(This article belongs to the Special Issue Application of Marine Nature Products to Reduce Oxidative Stress)

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22 pages, 1425 KiB

Open AccessArticle

Proteomic Analysis and Biochemical Characterization of the Nematocyst Extract of the Hydrozoan Velella velella

by Eleonora Tassara, Ivan Mikšík, Petr Pompach, Gian Luigi Mariottini, Liang Xiao, Marco Giovine and Marina Pozzolini

Mar. Drugs 2024, 22(10), 468; https://doi.org/10.3390/md22100468 (registering DOI) - 12 Oct 2024

Abstract

The venom contained within cnidarian nematocysts has a complex composition and holds significant potential for biotechnological applications. In this context, one of the most effective methods for studying nematocyst contents is the proteomic approach, which can detect even trace amounts of compounds while [...] Read more.

The venom contained within cnidarian nematocysts has a complex composition and holds significant potential for biotechnological applications. In this context, one of the most effective methods for studying nematocyst contents is the proteomic approach, which can detect even trace amounts of compounds while minimizing the need for large-scale animal collection, thus helping to preserve ecosystem integrity. This study aimed to provide a comprehensive proteomic and biochemical characterization of the crude nematocyst extract from the common hydrozoan Velella velella. Despite not being harmful to humans, the analysis of the crude venom extract from V. velella brought to the identification of 783 different proteins, categorized into structural components, enzymes, and potential toxins, revealing a qualitative composition of the venom similar to that of other more toxic cnidarians. Biochemical assays confirmed the presence of various active hydrolytic enzymes within the extract, including proteases, phospholipases, hyaluronidases, DNases, and chitinases. These findings pave the road for future studies involving the pharmacological applications of Velella velella venom components through recombinant production and functional testing. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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21 pages, 1301 KiB

Open AccessArticle

New Green Biorefinery Strategies to Valorize Bioactive Fractions from Palmaria palmata

by Melis Cokdinleyen, Gloria Domínguez-Rodríguez, Huseyin Kara, Elena Ibáñez and Alejandro Cifuentes

Mar. Drugs 2024, 22(10), 467; https://doi.org/10.3390/md22100467 (registering DOI) - 11 Oct 2024

Abstract

A biorefinery process was developed to isolate phycobiliproteins, sulfated polysaccharides, and phenolic compounds from Palmaria palmata. The extraction process was carried out in three stages using ultrasound-assisted extraction (UAE) and pressurized liquid extraction (PLE) integrated with different natural deep eutectic solvents (NaDESs). [...] Read more.

A biorefinery process was developed to isolate phycobiliproteins, sulfated polysaccharides, and phenolic compounds from Palmaria palmata. The extraction process was carried out in three stages using ultrasound-assisted extraction (UAE) and pressurized liquid extraction (PLE) integrated with different natural deep eutectic solvents (NaDESs). In general, PLE provided higher phycobiliprotein contents than UAE in the first step of the process. In fact, the hydrolysis product of the PLE-NaDES extracts achieved a higher antioxidant capacity than that of the UAE-NaDES extracts. Particularly, glycerol:glucose (2:1) with 50% water in combination with PLE was the most suitable NaDES to recover the highest phycobiliprotein, protein, and sulfated polysaccharide contents from Palmaria palmata in the first and second steps of the biorefinery process. Finally, a PLE-NaDES using choline chloride:glycerol (1:2) with 60% water as the NaDES was employed for the recovery of antioxidant and neuroprotective phenolic compounds from the residue of the second step, obtaining a higher total phenolic content than employing PLE with ethanol/water (70:30, v/v) as the extraction solvent. Moreover, a forced stability study revealed that the NaDESs provided a protective effect compared to the water extracts against the degradation of phycobiliproteins, preserving their color over time. This study contributes to the recovery of high-value components from an undervalued biomarine source through a sustainable biorefinery process. Full article

(This article belongs to the Special Issue The Extraction and Application of Functional Components in Algae)

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17 pages, 3897 KiB

Open AccessArticle

Blue Mussel-Derived Bioactive Peptides PIISVYWK (P1) and FSVVPSPK (P2): Promising Agents for Inhibiting Foam Cell Formation and Inflammation in Cardiovascular Diseases

by Chathuri Kaushalya Marasinghe and Jae-Young Je

Mar. Drugs 2024, 22(10), 466; https://doi.org/10.3390/md22100466 - 10 Oct 2024

Abstract

Atherosclerosis is a key etiological event in the development of cardiovascular diseases (CVDs), strongly linked to the formation of foam cells. This study explored the effects of two blue mussel-derived bioactive peptides (BAPs), PIISVYWK (P1) and FSVVPSPK (P2), on inhibiting foam cell formation [...] Read more.

Atherosclerosis is a key etiological event in the development of cardiovascular diseases (CVDs), strongly linked to the formation of foam cells. This study explored the effects of two blue mussel-derived bioactive peptides (BAPs), PIISVYWK (P1) and FSVVPSPK (P2), on inhibiting foam cell formation and mitigating inflammation in oxLDL-treated RAW264.7 macrophages. Both peptides significantly suppressed intracellular lipid accumulation and cholesterol levels while promoting cholesterol efflux by downregulating cluster of differentiation 36 (CD36) and class A1 scavenger receptors (SR-A1) and upregulating ATP binding cassette subfamily A member 1 (ABCA-1) and ATP binding cassette subfamily G member 1 (ABCG-1) expressions. The increased expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α) further validated their role in enhancing cholesterol efflux. Additionally, P1 and P2 inhibited foam cell formation in oxLDL-treated human aortic smooth muscle cells and exerted anti-inflammatory effects by reducing pro-inflammatory cytokines, nitric oxide (NO), prostaglandin E₂ (PGE₂), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), primarily through inhibiting NF-κB activation. Furthermore, P1 and P2 alleviated oxidative stress by activating the Nrf2/HO-1 pathway. Our findings demonstrate that P1 and P2 have significant potential in reducing foam cell formation and inflammation, both critical factors in atherosclerosis development. These peptides may serve as promising therapeutic agents for the prevention and treatment of CVDs associated with oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 4.0)

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19 pages, 8961 KiB

Open AccessArticle

Novel Insights into Ethanol-Soluble Oyster Peptide–Zinc-Chelating Agents: Structural Characterization, Chelation Mechanism, and Potential Protection on MEHP-Induced Leydig Cells

by Zhen Lu, Qianqian Huang, Xiaoming Qin, Fujia Chen, Enzhong Li and Haisheng Lin

Mar. Drugs 2024, 22(10), 465; https://doi.org/10.3390/md22100465 - 10 Oct 2024

Abstract

Numerous studies have reported that mono-(2-ethylhexyl) phthalate (MEHP) (bioactive metabolite of Di(2-ethylhexyl) phthalate) has inhibitory effects on Leydig cells. This study aims to prepare an oyster peptide–zinc complex (PEP-Zn) to alleviate MEHP-induced damage in Leydig cells. Zinc-binding peptides were obtained through the following [...] Read more.

Numerous studies have reported that mono-(2-ethylhexyl) phthalate (MEHP) (bioactive metabolite of Di(2-ethylhexyl) phthalate) has inhibitory effects on Leydig cells. This study aims to prepare an oyster peptide–zinc complex (PEP-Zn) to alleviate MEHP-induced damage in Leydig cells. Zinc-binding peptides were obtained through the following processes: zinc-immobilized affinity chromatography (IMAC-Zn²⁺), liquid chromatography–mass spectrometry technology (LC-MS/MS) analysis, molecular docking, molecular dynamic simulation, and structural characterization. Then, the Zn-binding peptide (PEP) named Glu—His—Ala—Pro—Asn—His—Asp—Asn—Pro—Gly—Asp—Leu (EHAPNHDNPGDL) was identified. EHAPNHDNPGDL showed the highest zinc-chelating ability of 49.74 ± 1.44%, which was higher than that of the ethanol-soluble oyster peptides (27.50 ± 0.41%). In the EHAPNHDNPGDL-Zn complex, Asn-5, Asp-7, Asn-8, His-2, and Asp-11 played an important role in binding to the zinc ion. Additionally, EHAPNHDNPGDL-Zn was found to increase the cell viability, significantly increase the relative activity of antioxidant enzymes and testosterone content, and decrease malondialdehyde (MDA) content in MEHP-induced TM3 cells. The results also indicated that EHAPNHDNPGDL-Zn could alleviate MEHP-induced apoptosis by reducing the protein level of p53, p21, and Bax, and increasing the protein level of Bcl-2. These results indicate that the zinc-chelating peptides derived from oyster peptides could be used as a potential dietary zinc supplement. Full article

(This article belongs to the Special Issue The Bioactive Potential of Marine-Derived Peptides and Proteins)

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25 pages, 3187 KiB

Open AccessArticle

Characterization of Unfractionated Polysaccharides in Brown Seaweed by Methylation-GC-MS-Based Linkage Analysis

by Barinder Bajwa, Xiaohui Xing, Spencer C. Serin, Maria Hayes, Stephanie A. Terry, Robert J. Gruninger and D. Wade Abbott

Mar. Drugs 2024, 22(10), 464; https://doi.org/10.3390/md22100464 - 9 Oct 2024

Abstract

This study introduces a novel approach to analyze glycosidic linkages in unfractionated polysaccharides from alcohol-insoluble residues (AIRs) of five brown seaweed species. GC-MS analysis of partially methylated alditol acetates (PMAAs) enables monitoring and comparison of structural variations across different species, harvest years, and [...] Read more.

This study introduces a novel approach to analyze glycosidic linkages in unfractionated polysaccharides from alcohol-insoluble residues (AIRs) of five brown seaweed species. GC-MS analysis of partially methylated alditol acetates (PMAAs) enables monitoring and comparison of structural variations across different species, harvest years, and tissues with and without blanching treatments. The method detects a wide array of fucose linkages, highlighting the structural diversity in glycosidic linkages and sulfation position in fucose-containing sulfated polysaccharides. Additionally, this technique enhances cellulose quantitation, overcoming the limitations of traditional monosaccharide composition analysis that typically underestimates cellulose abundance due to incomplete hydrolysis of crystalline cellulose. The introduction of a weak methanolysis-sodium borodeuteride reduction pretreatment allows for the detection and quantitation of uronic acid linkages in alginates. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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15 pages, 3533 KiB

Open AccessArticle

The Marine Antimicrobial Peptide AOD with Intact Disulfide Bonds Has Remarkable Antibacterial and Anti-Biofilm Activity

by Ruoyu Mao, Qingyi Zhao, Haiqiang Lu, Na Yang, Yuanyuan Li, Da Teng, Ya Hao, Xinxi Gu and Jianhua Wang

Mar. Drugs 2024, 22(10), 463; https://doi.org/10.3390/md22100463 - 8 Oct 2024

Abstract

American Oyster Defensin (AOD) is a marine peptide that is derived from North American mussels. It has been demonstrated to exhibit potent antimicrobial activity and high safety in both in vitro and in vivo models. In this study, to facilitate synthesis, mutants of [...] Read more.

American Oyster Defensin (AOD) is a marine peptide that is derived from North American mussels. It has been demonstrated to exhibit potent antimicrobial activity and high safety in both in vitro and in vivo models. In this study, to facilitate synthesis, mutants of AOD with fewer disulfide bonds were designed and subjected to structural, antimicrobial, and anti-biofilm analysis. The antimicrobial activity of AOD-derived peptides decreased after reduction in the disulfide bond, and among its three derivatives, only AOD-1 inhibited very few bacteria with a MIC value of 64 μg/mL, whereas the others had no inhibitory effect on pathogenic bacteria. The findings demonstrated that full disulfide bonds are indispensable for bactericidal activity, with the α-helix playing a pivotal role in inhibiting bacterial membranes. Furthermore, the results of the ATP, ROS, membrane potential, and membrane fluidity assays demonstrated that intracellular ATP, reactive oxygen species, and membrane fluidity were all increased, while membrane potential was reduced. This indicated that AOD resulted in the impairment of membrane fluidity and induced metabolic disorders, ultimately leading to bacterial death. The inhibitory effect of AOD on the biofilm of S. epidermidis G-81 was determined through the crystal violet and confocal microscopy. The results demonstrated that AOD exhibited a notable inhibitory impact on the biofilm of S. epidermidis G-81. The minimum biofilm inhibitory concentration of AOD on S. epidermidis G-81 was 16 μg/mL, and the minimum biofilm scavenging concentration was 32 μg/mL, which exhibited superior efficacy compared to that of lincomycin. The inhibitory effect on the primary biofilm was 90.3%, and that on the mature biofilm was 82.85%, with a dose-dependent inhibition effect. Concurrently, AOD cleared intra-biofilm organisms and reduced the number of biofilm-holding bacteria by six orders of magnitude. These data indicate that disulfide bonds are essential to the structure and activity of AOD, and AOD may potentially become an effective dual-action antimicrobial and anti-biofilm agent. Full article

(This article belongs to the Special Issue Marine Natural Products with Antifouling Activity, 3rd Edition)

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16 pages, 3607 KiB

Open AccessArticle

Modified Hemocyanins from Rapana thomasiana and Helix aspersa Exhibit Strong Antitumor Activity in the B16F10 Mouse Melanoma Model

by Emiliya Stoyanova, Nikolina Mihaylova, Nikola Ralchev, Silviya Bradyanova, Iliyan Manoylov, Yuliana Raynova, Krassimira Idakieva and Andrey Tchorbanov

Mar. Drugs 2024, 22(10), 462; https://doi.org/10.3390/md22100462 - 7 Oct 2024

Abstract

Melanoma is one of the most common tumors worldwide, and new approaches and antitumor drugs for therapy are being investigated. Among the promising biomolecules of natural origin for antitumor research are gastropodan hemocyanins—highly immunogenic multimeric glycoproteins used as antitumor agents and components of [...] Read more.

Melanoma is one of the most common tumors worldwide, and new approaches and antitumor drugs for therapy are being investigated. Among the promising biomolecules of natural origin for antitumor research are gastropodan hemocyanins—highly immunogenic multimeric glycoproteins used as antitumor agents and components of therapeutic vaccines in human and mouse cancer models. A murine melanoma model established in C57BL/6 mice of the B16F10 cell line was used to study anticancer modified oxidized hemocyanins (Ox-Hcs) that were administered to experimental animals (100 μg/mouse) under different regimens: mild, intensive, and with sensitization. The solid tumor growth, antitumor response, cell infiltration in tumors, and survival were assessed using flow cytometry, ELISA, and cytotoxicity assays. Therapy with Ox-RtH or Ox-HaH resulted in the generation of enhanced specific immune response (increased levels of tumor-infiltrated mature NK cells (CD27+CD11b+) in sensitized groups and of macrophages in the intensively immunized animals) and tumor suppression. Beneficial effects such as delayed tumor incidence and growth as well as prolonged survival of tumor-bearing animals have been observed. High levels of melanoma-specific CTLs that mediate cytotoxic effects on tumor cells; tumor-infiltrating IgM antibodies expected to enhance antibody-dependent cellular cytotoxicity; type M1 macrophages, which stimulate the Th1 response and cytotoxic cells; and proinflammatory cytokines, were also observed after Ox-Hcs administration. The modified Hcs showed strong antitumor properties in different administration regimens in a murine model of melanoma with potential for future application in humans. Full article

(This article belongs to the Special Issue Marine Proteins and Enzymes: Bioactivities and Medicinal Applications)

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12 pages, 2383 KiB

Open AccessArticle

The Antioxidant Effects of Trypsin-Hydrolysate Derived from Abalone Viscera and Fishery By-Products, and the Angiotensin-I Converting Enzyme (ACE) Inhibitory Activity of Its Purified Bioactive Peptides

by Jun-Ho Heo, Eun-A Kim, Nalae Kang, Seong-Yeong Heo, Ginnae Ahn and Soo-Jin Heo

Mar. Drugs 2024, 22(10), 461; https://doi.org/10.3390/md22100461 - 7 Oct 2024

Abstract

Abalone is a rich source of nutrition, the viscera of which are discarded as by-product during processing. This study explored the biological activities of peptides derived from abalone viscera (AV). Trypsin-hydrolysate of AV (TAV) was purified into three fractions using a Sephadex G-10 [...] Read more.

Abalone is a rich source of nutrition, the viscera of which are discarded as by-product during processing. This study explored the biological activities of peptides derived from abalone viscera (AV). Trypsin-hydrolysate of AV (TAV) was purified into three fractions using a Sephadex G-10 column. Nine bioactive peptides (VAR, NYER, LGPY, VTPGLQY, QFPVGR, LGEW, QLQFPVGR, LDW, and NLGEW) derived from TAV-F2 were sequenced. LGPY, VTPGLQY, LGEW, LDW, and NLGEW exhibited antioxidant properties, with IC₅₀ values of 0.213, 0.297, 0.289, 0.363, and 0.303 mg/mL, respectively. In vitro analysis determined that the peptides VAR, NYER, VTPGLQY, QFPVGR, LGEW, QLQFPVGR, and NLGEW inhibited ACE, with IC₅₀ values of 0.104, 0.107, 0.023, 0.023, 0.165, 0.004, and 0.146 mg/mL, respectively. The binding interactions of ACE-bioactive peptide complexes were investigated using docking analysis with the ZDCOK server. VTPGLQT interacted with HIS513 and TYR523, and QLQFPVGR interacted with HIS353, ALA354, GLU384, HIS513, and TYR523, contributing to the inhibition of ACE activity. They also interacted with amino acids that contribute to stability by binding to zinc ions. QFPVGR may form complexes with ACE surface sites, suggesting indirect inhibition. These results indicate that AV is a potential source of bioactive peptides with dual antioxidant and anti-hypertensive dual effects. Full article

(This article belongs to the Special Issue Fishery Discards, Processing Waste and Marine By-Products)

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24 pages, 2371 KiB

Open AccessReview

Microalgal Phenolics: Systematic Review with a Focus on Methodological Assessment and Meta-Analysis

by Vasilis Andriopoulos and Michael Kornaros

Mar. Drugs 2024, 22(10), 460; https://doi.org/10.3390/md22100460 - 7 Oct 2024

Abstract

A critical review and analysis of the literature relevant to the phenolic content of eucaryotic microalgae was performed. Several issues were identified and discussed. In summary, the main problems with the reporting on the phenolic content of microalgae are the following: (1) despite [...] Read more.

A critical review and analysis of the literature relevant to the phenolic content of eucaryotic microalgae was performed. Several issues were identified and discussed. In summary, the main problems with the reporting on the phenolic content of microalgae are the following: (1) despite its usefulness in the determination of phenolic content in plant samples, the Folin–Ciocalteu assay is non-suitable for microalgal research due to the high presence of interfering compounds in microalgal extracts such as chlorophyll and its derivatives in organic extracts and free aromatic amino acids or nucleotides in aqueous extracts; (2) while there is chromatographic evidence for the presence of simple phenolic acids in most microalgal clades, the lack of critical enzymes of phenolic biosynthesis in most microalgae, as well as the high variability of phenolic profiles even in the same genus, require more extensive research before conclusions are drawn; (3) the accumulation and metabolism of external phenolics by microalgae has been almost universally neglected in studies focusing on the phenolic content of microalgae, even when natural seawater or complex organic media are used in the cultivation process. Despite these issues, the literature focusing on the bioremediation of waste streams rich in phenolics through microalgae demonstrates the ability of those organisms to adsorb, internalize, and in many cases oxidize or transform a wide range of phenolic compounds, even at very high concentrations. Simple phenolics found in waste streams, such as olive mill waste, have been shown to enhance the antioxidant activity and various bioactivities of microalgal extracts, while complex biotransformation products of phenolics have also been characterized. In conclusion, the de novo biosynthesis of phenolic compounds via eucaryotic microalgae requires further investigation with better designed experiments and suitable analytical methods, while the response of microalgae to phenolic compounds in their growth medium is of great practical interest, both in terms of waste treatment and for the production of functional foods, cosmetics, and pharmaceuticals. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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18 pages, 4586 KiB

Open AccessArticle

Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer

by Ru-Yi Chen, Li-Jian Ding, Yan-Jun Liu, Jin-Jin Shi, Jing Yu, Chang-Yun Li, Jian-Fei Lu, Guan-Jun Yang and Jiong Chen

Mar. Drugs 2024, 22(10), 459; https://doi.org/10.3390/md22100459 - 5 Oct 2024

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This [...] Read more.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression. Full article

(This article belongs to the Special Issue Discovery of Marine-Derived Anticancer Agents)

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24 pages, 3380 KiB

Open AccessArticle

Investigating Non-Native Ribbon Worm Cephalothrix simula as a Potential Source of Tetrodotoxin in British Bivalve Shellfish

by Monika Dhanji-Rapkova, Robert G. Hatfield, David I. Walker, Chantelle Hooper, Sarah Alewijnse, Craig Baker-Austin, Andrew D. Turner and Jennifer M. Ritchie

Mar. Drugs 2024, 22(10), 458; https://doi.org/10.3390/md22100458 - 5 Oct 2024

Abstract

Tetrodotoxin (TTX) is a potent marine neurotoxin found in several phylogenetically diverse organisms, some of which are sought as seafood. Since 2015, TTX has been reported in bivalve shellfish from several estuarine locations along the Mediterranean and European Atlantic coasts, posing an emerging [...] Read more.

Tetrodotoxin (TTX) is a potent marine neurotoxin found in several phylogenetically diverse organisms, some of which are sought as seafood. Since 2015, TTX has been reported in bivalve shellfish from several estuarine locations along the Mediterranean and European Atlantic coasts, posing an emerging food safety concern. Although reports on spatial and temporal distribution have increased in recent years, processes leading to TTX accumulation in European bivalves are yet to be described. Here, we explored the hypothesis that the ribbon worm species Cephalothrix simula, known to contain high levels of TTX, could play a role in the trophic transfer of the toxin into shellfish. During a field study at a single location in southern England, we confirmed C. simula DNA in seawater adjacent to trestle-farmed Pacific oysters Magallana gigas (formerly Crassostrea gigas) with a history of TTX occurrence. C. simula DNA in seawater was significantly higher in June and July during the active phase of toxin accumulation compared to periods of either no or continually decreasing TTX concentrations in M. gigas. In addition, C. simula DNA was detected in oyster digestive glands collected on 15 June 2021, the day with the highest recorded C. simula DNA abundance in seawater. These findings show evidence of a relationship between C. simula and TTX occurrence, providing support for the hypothesis that bivalves may acquire TTX through filter-feeding on microscopic life forms of C. simula present in the water column at particular periods each year. Although further evidence is needed to confirm such feeding activity, this study significantly contributes to discussions about the biological source of TTX in European bivalve shellfish. Full article

(This article belongs to the Special Issue Emerging Toxins Accumulation in Shellfish)

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21 pages, 619 KiB

Open AccessReview

Investigating the Anti-Inflammatory Activity of Various Brown Algae Species

by Selin Ersoydan and Thomas Rustemeyer

Mar. Drugs 2024, 22(10), 457; https://doi.org/10.3390/md22100457 - 5 Oct 2024

Abstract

This literature review investigated the anti-inflammatory properties of brown algae, emphasizing their potential for dermatological applications. Due to the limitations and side effects associated with corticosteroids and immunomodulators, interest has been growing in harnessing therapeutic qualities from natural products as alternatives to traditional [...] Read more.

This literature review investigated the anti-inflammatory properties of brown algae, emphasizing their potential for dermatological applications. Due to the limitations and side effects associated with corticosteroids and immunomodulators, interest has been growing in harnessing therapeutic qualities from natural products as alternatives to traditional treatments for skin inflammation. This review explored the bioactive compounds in brown algae, specifically looking into two bioactive compounds, namely, fucoidans and phlorotannins, which are widely known to exhibit anti-inflammatory properties. This review synthesized the findings from various studies, highlighting how these compounds can mitigate inflammation by mechanisms such as reducing oxidative stress, inhibiting protein denaturation, modulating immune responses, and targeting inflammatory pathways, particularly in conditions like atopic dermatitis. The findings revealed species-specific variations influenced by the molecular weight and sulphate content. Challenges related to skin permeability were addressed, highlighting the potential of nanoformulations and penetration enhancers to improve delivery. While the in vivo results using animal models provided positive results, further clinical trials are necessary to confirm these outcomes in humans. This review concludes that brown algae hold substantial promise for developing new dermatological treatments and encourages further research to optimize extraction methods, understand the molecular mechanisms, and address practical challenges such as sustainability and regulatory compliance. This review contributes to the growing body of evidence supporting the integration of marine-derived compounds into therapeutic applications for inflammatory skin diseases. Full article

(This article belongs to the Special Issue From Sea to Skin: Advancements in Marine-Based Cosmeceuticals)

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18 pages, 3725 KiB

Open AccessArticle

Potential of Marine Sponge Metabolites against Prions: Bromotyrosine Derivatives, a Family of Interest

by Maha Sinane, Colin Grunberger, Lucile Gentile, Céline Moriou, Victorien Chaker, Pierre Coutrot, Alain Guenneguez, Marie-Aude Poullaouec, Solène Connan, Valérie Stiger-Pouvreau, Mayalen Zubia, Yannick Fleury, Stéphane Cérantola, Nelly Kervarec, Ali Al-Mourabit, Sylvain Petek and Cécile Voisset

Mar. Drugs 2024, 22(10), 456; https://doi.org/10.3390/md22100456 - 4 Oct 2024

Abstract

The screening of 166 extracts from tropical marine organisms (invertebrates, macroalgae) and 3 cyclolipopeptides from microorganisms against yeast prions highlighted the potential of Verongiida sponges to prevent the propagation of prions. We isolated the known compounds purealidin Q (1), aplysamine-2 ( [...] Read more.

The screening of 166 extracts from tropical marine organisms (invertebrates, macroalgae) and 3 cyclolipopeptides from microorganisms against yeast prions highlighted the potential of Verongiida sponges to prevent the propagation of prions. We isolated the known compounds purealidin Q (1), aplysamine-2 (2), pseudoceratinine A (3), aerophobin-2 (4), aplysamine-1 (5), and pseudoceratinine B (6) for the first time from the Wallisian sponge Suberea laboutei. We then tested compounds 1–6 and sixteen other bromotyrosine and bromophenol derivatives previously isolated from Verongiida sponges against yeast prions, demonstrating the potential of 1–3, 5, 6, aplyzanzine C (7), purealidin A (10), psammaplysenes D (11) and F (12), anomoian F (14), and N,N-dimethyldibromotyramine (15). Following biological tests on mammalian cells, we report here the identification of the hitherto unknown ability of the six bromotyrosine derivatives 1, 2, 5, 7, 11, and 14 of marine origin to reduce the spread of the PrP^Sc prion and the ability of compounds 1 and 2 to reduce endoplasmic reticulum stress. These two biological activities of these bromotyrosine derivatives are, to our knowledge, described here for the first time, offering a new therapeutic perspective for patients suffering from prion diseases that are presently untreatable and consequently fatal. Full article

(This article belongs to the Section Marine Pharmacology)

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25 pages, 7587 KiB

Open AccessArticle

Exploring Marine-Derived Compounds: In Silico Discovery of Selective Ketohexokinase (KHK) Inhibitors for Metabolic Disease Therapy

by Mansour S. Alturki

Mar. Drugs 2024, 22(10), 455; https://doi.org/10.3390/md22100455 - 3 Oct 2024

Abstract

The increasing prevalence of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes, poses significant global health challenges. Ketohexokinase (KHK), an enzyme crucial in fructose metabolism, is a potential therapeutic target due to its role in these conditions. This [...] Read more.

The increasing prevalence of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes, poses significant global health challenges. Ketohexokinase (KHK), an enzyme crucial in fructose metabolism, is a potential therapeutic target due to its role in these conditions. This study focused on the discovery of selective KHK inhibitors using in silico methods. We employed structure-based drug design (SBDD) and ligand-based drug design (LBDD) approaches, beginning with molecular docking to identify promising compounds, followed by induced-fit docking (IFD), molecular mechanics generalized Born and surface area continuum solvation (MM-GBSA), and molecular dynamics (MD) simulations to validate binding affinities. Additionally, shape-based screening was conducted to assess structural similarities. The findings highlight several potential inhibitors with favorable ADMET profiles, offering promising candidates for further development in the treatment of fructose-related metabolic disorders. Full article

(This article belongs to the Collection Marine Drugs in the Management of Metabolic Diseases)

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9 pages, 2040 KiB

Open AccessArticle

Total Synthesis of Talarolide A and atrop-Talarolide A: Hydroxamate H-Bond Bridge Stabilization of Cyclic Peptide Conformers Invokes Non-Canonical Atropisomerism

by Waleed M. Hussein, Yuxuan Zhu, Angela A. Salim and Robert J. Capon

Mar. Drugs 2024, 22(10), 454; https://doi.org/10.3390/md22100454 - 3 Oct 2024

Abstract

The first total synthesis of the Australian marine tunicate fungus-derived cyclic peptide talarolide A (1) has confirmed the structure previously proposed on the basis of spectroscopic and chemical analyses and re-affirmed the importance of the unique hydroxamate H-bond bridge in ring [...] Read more.

The first total synthesis of the Australian marine tunicate fungus-derived cyclic peptide talarolide A (1) has confirmed the structure previously proposed on the basis of spectroscopic and chemical analyses and re-affirmed the importance of the unique hydroxamate H-bond bridge in ring conformer stabilization. The unexpected co-synthesis of atrop-talarolide A (8) revealed, for the first time, that hydroxamate H-bond bridging in the talarolide framework invokes non-canonical atropisomerism and that talarolides A (1), C (3), and D (4) all exist naturally as atropisomers. These discoveries raise the intriguing prospect that comparable functionalisation of other cyclic peptides, including those with commercial value, could provide ready access to new “unnatural atropisomeric” chemical space, with new and/or improved chemical and biological properties. Full article

(This article belongs to the Special Issue Synthetic Chemistry in Marine Drug Discovery: Challenges and Opportunities)

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20 pages, 7887 KiB

Open AccessArticle

Degradation of Natural Undaria pinnatifida into Unsaturated Guluronic Acid Oligosaccharides by a Single Alginate Lyase

by Hui Wang, Jiaqi Wen, Nuraliya Ablimit, Kun Deng, Wenzhuo Wang and Wei Jiang

Mar. Drugs 2024, 22(10), 453; https://doi.org/10.3390/md22100453 - 2 Oct 2024

Abstract

Here, we report on a bifunctional alginate lyase (Vnalg7) expressed in Pichia pastoris, which can degrade natural Undaria pinnatifida into unsaturated guluronic acid di- and trisaccharide without pretreatment. The enzyme activity of Vnalg7 (3620.00 U/mL-culture) was 15.81-fold higher than that of the [...] Read more.

Here, we report on a bifunctional alginate lyase (Vnalg7) expressed in Pichia pastoris, which can degrade natural Undaria pinnatifida into unsaturated guluronic acid di- and trisaccharide without pretreatment. The enzyme activity of Vnalg7 (3620.00 U/mL-culture) was 15.81-fold higher than that of the original alg (228.90 U/mL-culture), following engineering modification. The degradation rate reached 52.75%, and reducing sugar reached 30.30 mg/mL after combining Vnalg7 (200.00 U/mL-culture) and 14% (w/v) U. pinnatifida for 6 h. Analysis of the action mode indicated that Vnalg7 could degrade many substrates to produce a variety of unsaturated alginate oligosaccharides (AOSs), and the minimal substrate was tetrasaccharide. Site-directed mutagenesis showed that Glu²³⁸, Glu²⁴¹, Glu³¹², Arg²³⁶, His³⁰⁷, Lys⁴¹⁴, and Tyr⁴¹⁸ are essential catalytic sites, while Glu³³⁴, Glu³⁴⁴, and Asp³¹¹ play auxiliary roles. Mechanism analysis revealed the enzymatic degradation pattern of Vnalg7, which mainly recognizes and attacks the third glycosidic linkage from the reducing end of oligosaccharide substrate. Our findings provide a novel alginate lyase tool and a sustainable and commercial production strategy for value-added biomolecules using seaweeds. Full article

(This article belongs to the Special Issue Marine Polysaccharides and Oligosaccharides: Extraction and Biological Activities)

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38 pages, 2392 KiB

Open AccessArticle

Exploring the Physicochemical Characteristics of Marine Protein Hydrolysates and the Impact of In Vitro Gastrointestinal Digestion on Their Bioactivity

by Deepanshi Sharma, Snehal Gite and Maria G. Tuohy

Mar. Drugs 2024, 22(10), 452; https://doi.org/10.3390/md22100452 - 1 Oct 2024

Abstract

Fish protein hydrolysates (FPHs) were obtained from different fish sources using a combination of microbial enzymes. The industrially produced FPHs from blue whiting (Micromesistius poutassou) and sprat (Sprattus sprattus) were compared to freeze-dried FPHs generated in-house from hake ( [...] Read more.

Fish protein hydrolysates (FPHs) were obtained from different fish sources using a combination of microbial enzymes. The industrially produced FPHs from blue whiting (Micromesistius poutassou) and sprat (Sprattus sprattus) were compared to freeze-dried FPHs generated in-house from hake (Merluccius merluccius) and mackerel (Scomber scombrus) in terms of their physicochemical composition and functionality. Significant differences (p < 0.05) were observed in the protein, moisture, and ash contents of the FPHs, with the majority having high levels of protein (73.24–89.31%). Fractions that were more extensively hydrolysed exhibited a high solubility index (74.05–98.99%) at different pHs. Blue whiting protein hydrolysate-B (BWPH-B) had the highest foaming capacity at pH 4 (146.98 ± 4.28%) and foam stability over 5 min (90–100%) at pH 4, 6, and 8. The emulsifying capacity ranged from 61.11–108.90 m²/g, while emulsion stability was 37.82–76.99% at 0.5% (w/v) concentration. In terms of peptide bioactivity, sprat protein hydrolysate (SPH) had the strongest overall reducing power. The highest Cu²⁺ chelating activity was exhibited by hake protein hydrolysate (HPH) and mackerel protein hydrolysate (MPH), with IC₅₀ values of 0.66 and 0.78 mg protein/mL, respectively, while blue whiting protein hydrolysate-A (BWPH-A) had the highest activity against Fe²⁺ (IC₅₀ = 1.89 mg protein/mL). SPH scavenged DPPH and ABTS radicals best with IC₅₀ values of 0.73 and 2.76 mg protein/mL, respectively. All FPHs displayed noteworthy scavenging activity against hydroxyl radicals, with IC₅₀ values ranging from 0.48–3.46 mg protein/mL. SPH and MPH showed the highest scavenging potential against superoxide radicals with IC₅₀ values of 1.75 and 2.53 mg protein/mL and against hydrogen peroxide with 2.22 and 3.66 mg protein/mL, respectively. While inhibition of α-glucosidase was not observed, the IC₅₀ values against α-amylase ranged from 8.81–18.42 mg protein/mL, with SPH displaying the highest activity. The stability of FPHs following simulated gastrointestinal digestion (SGID) showed an irregular trend. Overall, the findings suggest that marine-derived protein hydrolysates may serve as good sources of natural nutraceuticals with antioxidant and antidiabetic properties. Full article

(This article belongs to the Special Issue Enzymes from Marine By-Products and Wastes)

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15 pages, 3342 KiB

Open AccessArticle

Cognitive-Enhancing Effect of Marine Brown Algae-Derived Phenolics through S100B Inhibition and Antioxidant Activity in the Rat Model of Ischemic Stroke

by Jurairat Khongrum, Pratoomporn Yingthongchai, Suriya Tateing and Pratchaya Kaewkaen

Mar. Drugs 2024, 22(10), 451; https://doi.org/10.3390/md22100451 - 1 Oct 2024

Abstract

Cognitive impairments are frequently reported after ischemic strokes. Novel and effective treatments are required. This study aimed to develop a functional ingredient obtained from marine algae and to determine the effect of the extract on antioxidative stress, as well as neuroprotective effects, in [...] Read more.

Cognitive impairments are frequently reported after ischemic strokes. Novel and effective treatments are required. This study aimed to develop a functional ingredient obtained from marine algae and to determine the effect of the extract on antioxidative stress, as well as neuroprotective effects, in a rat model of MCAO-induced ischemic stroke. Among the selected marine algal extracts, Sargassum polycystum displayed the highest total phenolic content and antioxidative potential, and was subsequently used to evaluate cognitive function in rat models of ischemic stroke. The S. polycystum extract, administered at doses of 100, 300, and 500 mg/kg BW, significantly improved cognitive function by enhancing cognitive performance in the Morris water maze and novel object recognition tests. Biochemical changes revealed that providing S. polycystum increased the activities of SOD, CAT, and GSH-Px by 52.48%, 50.77%, and 66.20%, respectively, and decreased the concentrations of MDA by 51.58% and S100B by 36.64% compared to the vehicle group. These findings suggest that S. polycystum extract may mitigate cognitive impairment in ischemic stroke by reducing oxidative stress and inhibiting S100B expression, thus highlighting its potential as a functional ingredient for drugs and nutraceuticals aimed at neuroprotection. Full article

(This article belongs to the Special Issue Therapeutic Potential of Marine Algae)

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