Marine Drugs

23 pages, 3637 KB

Open AccessArticle

Screening and Assessment of Hypoglycemic Active Peptide from Natural Edible Pigment Phycobiliprotein Based on Molecular Docking, Network Pharmacology, Enzyme Inhibition Assay Analyses, and Cell Experiments

by Zhimin Zhu, Yan Zhang, Bingbing He, Limin He, Guihong Fang, Yi Ning, Pengcheng Fu and Jing Liu

Mar. Drugs 2025, 23(8), 331; https://doi.org/10.3390/md23080331 - 17 Aug 2025

Viewed by 1089

Abstract

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate [...] Read more.

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics. Full article

(This article belongs to the Special Issue Marine Nutraceuticals and Functional Foods: 2nd Edition)

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21 pages, 3929 KB

Open AccessArticle

Heterologous Expression and Antimicrobial Targets of a Novel Glycine-Rich Antimicrobial Peptide from Artemia franciscana

by Ming Tao, Aobo Sun, Huishi Shao, Huaiyuan Ye, Guangming Yu, Daigeng Chen and Wei Zhang

Mar. Drugs 2025, 23(8), 330; https://doi.org/10.3390/md23080330 - 17 Aug 2025

Viewed by 987

Abstract

The growing problem of antimicrobial resistance in aquaculture, caused by the excessive and unregulated use of antibiotics, highlights the critical necessity for developing new anti-infective solutions. Based on the characteristics of glycine-rich antimicrobial peptides (AMPs) and transcriptomic data, an antimicrobial peptide, namely Af [...] Read more.

The growing problem of antimicrobial resistance in aquaculture, caused by the excessive and unregulated use of antibiotics, highlights the critical necessity for developing new anti-infective solutions. Based on the characteristics of glycine-rich antimicrobial peptides (AMPs) and transcriptomic data, an antimicrobial peptide, namely AfRgly1, was discovered in this study. Subsequently, the peptide was obtained through heterologous expression in E. coli, and its antibacterial spectrum was determined. Molecular dynamics simulation and molecular biology experiments were conducted to explore the antibacterial target of AfRgly1. Results showed that the mRNA expression level of AfRgly1 was significantly upregulated after Vibrio alginolyticus infection. AfRgly1 has broad-spectrum antibacterial activity targeting on bacterial cell membrane, and it may also interact with bacterial DNA. AfRgly1 displayed low selectivity for fish red blood cells. These results indicate that AfRgly1 is an antimicrobial peptide with considerable potential for application in the development of therapeutic agents. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential, 5th Edition)

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11 pages, 3752 KB

Open AccessArticle

Discovery of a Hepatoprotective Trinor-Sesterterpenoid from the Marine Fungus Talaromyces sp. Against Hepatic Ischemia-Reperfusion Injury

by Wenxun Lan, Jian Cai, Liyan Yan, Xinyi Wu, Lisha Zhang, Chunmei Chen, Zhongqiu Liu, Xuefeng Zhou and Lan Tang

Mar. Drugs 2025, 23(8), 329; https://doi.org/10.3390/md23080329 - 16 Aug 2025

Viewed by 771

Abstract

A new trinor-sesterterpenoid penitalarin D (1), with a 3,6-dioxabicyclo[3.1.0]hexane moiety, as well as two known compounds, penitalarin C (2) and nafuredin A (3), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Their structures were determined [...] Read more.

A new trinor-sesterterpenoid penitalarin D (1), with a 3,6-dioxabicyclo[3.1.0]hexane moiety, as well as two known compounds, penitalarin C (2) and nafuredin A (3), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Their structures were determined by detailed NMR, MS spectroscopic analyses, and ECD calculations. Penitalarin D (1) and nafuredin A (3) showed toxicity or no toxicity against HepG2 cells at a concentration of 200 μM. The transcriptome sequencing and bioinformatics analysis revealed that 3 could be effective by regulating ferroptosis pathways in HepG2 cells, which was subsequently validated by RT-qPCR, demonstrating significant upregulation of ferroptosis-related genes. Pre-treatment with 3 could mitigate hypoxia-reoxygenation-induced damage in the oxygen glucose deprivation/reperfusion (OGD/R) cell model. Given the structural similarity of compounds 1, 2, and 3, we also screened compounds 1 and 2 in an AML12 OGD/R model. As no significant activity was observed, compound 3 was selected for subsequent in vivo studies. Subsequently, in vivo experiments demonstrated that 3 could significantly decrease pro-inflammatory cytokines and display the hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI). These findings identified nafuredin A (3) as a promising hepatoprotective agent for new drug development. Full article

(This article belongs to the Special Issue Selected Papers from the 2025 Symposium on Marine Microbiology in China)

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17 pages, 1734 KB

Open AccessArticle

The Efficacy of Daily Salmon Oil for Adult Type 2 Asthma: An Exploratory Randomized Double-Blind Trial

by Katarina Mølsæter, Kjetil Roth, Tor Åge Myklebust, Erland Hermansen, Dave Singh, Crawford Currie and Dag Arne Lihaug Hoff

Mar. Drugs 2025, 23(8), 328; https://doi.org/10.3390/md23080328 - 15 Aug 2025

Viewed by 915

Abstract

Asthma is a heterogeneous chronic respiratory condition with distinct inflammatory phenotypes, including type 2-driven eosinophilic asthma. This randomized, double-blind, placebo-controlled exploratory trial investigated the effects of OmeGO^®, on respiratory outcomes in adults with type 2 asthma. Over a 20-week period, 66 [...] Read more.

Asthma is a heterogeneous chronic respiratory condition with distinct inflammatory phenotypes, including type 2-driven eosinophilic asthma. This randomized, double-blind, placebo-controlled exploratory trial investigated the effects of OmeGO^®, on respiratory outcomes in adults with type 2 asthma. Over a 20-week period, 66 participants received 6 g per day of either OmeGO^® (≥120 mg eicosapentaenoic acid (EPA), ≥180 mg docosahexaenoic acid (DHA)), or placebo. The key outcome was a composite score of moderate and severe exacerbation events. Asthma control was assessed using the Asthma Control Questionnaire-5-item (ACQ5) and the Global Initiative for Asthma (GINA) criteria. The median time to the first composite event was 37 days (95% CI 9–47) in the OmeGO group and 15 days (95% CI 12–33) in the placebo group (p = 0.347); 73% of the participants in the OmeGO experienced at least one exacerbation compared to 82% in the placebo group (p = 0.347). The weekly frequence of composite events was 0.36 per day in the OmeGO group and 0.32 in the placebo group (p = 0.777). Even though there are no differences in the exacerbation rates between groups, the time to first composite event should be further explored. Full article

(This article belongs to the Section Marine Pharmacology)

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19 pages, 2470 KB

Open AccessArticle

New Marine-Inspired Oxadiazole Derivatives for Use Against Pancreatic Ductal Adenocarcinoma

by Camilla Pecoraro, Daniela Carbone, Fares Hezam Mohammed Al Ostoot, Mahrou Vahabi, Giulia Lencioni, Patrizia Diana, Elisa Giovannetti and Barbara Parrino

Mar. Drugs 2025, 23(8), 327; https://doi.org/10.3390/md23080327 - 14 Aug 2025

Viewed by 789

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with limited effective therapeutic options due to late diagnosis, aggressive progression, and rapid development of drug resistance. In pursuit of novel treatments, this study reports the design, synthesis, and biological evaluation of a [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with limited effective therapeutic options due to late diagnosis, aggressive progression, and rapid development of drug resistance. In pursuit of novel treatments, this study reports the design, synthesis, and biological evaluation of a new series of topsentin derivatives, featuring a 1,2,4-oxadiazole core. The newly synthesized derivatives were screened for antiproliferative activity against multiple PDAC cell lines (SUIT-2, Patu-T, and PANC-1), identifying several compounds with potent growth-inhibitory effects, particularly on SUIT-2 and Patu-T cells. Further studies demonstrated that these compounds also significantly inhibited cell migration and reduced clonogenic potential, with IC₅₀ values in the micromolar range. The results suggest that these marine-inspired 1,2,4-oxadiazole derivatives effectively target key hallmarks of PDAC, including proliferation, migration, and colony formation, supporting their further development as promising candidates for overcoming drug resistance and metastatic progression in pancreatic cancer. Full article

(This article belongs to the Section Marine Pharmacology)

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22 pages, 7562 KB

Open AccessArticle

Mannan-Containing Polymers from Hadal Bacterium Psychrobacter pulmonis: Preparation, Structural Analysis, Immunological Activity and Antitumor Effects

by Mingxing Qi, Shuqiang Yan, Yukun Cui, Yanan Huang, Yang Liu, Wenhui Wu, Xi Yu and Peipei Wang

Mar. Drugs 2025, 23(8), 326; https://doi.org/10.3390/md23080326 - 12 Aug 2025

Viewed by 857

Abstract

Microbial exopolysaccharides from extreme environments are increasingly becoming valuable candidates for drug development. In this study, four fractions named XL-1, XMRS-1, XL-1-D, and XMRS-1-D were isolated and purified from the hadal bacterium Psychrobacter pulmonis by column chromatography. The structural features of these fractions [...] Read more.

Microbial exopolysaccharides from extreme environments are increasingly becoming valuable candidates for drug development. In this study, four fractions named XL-1, XMRS-1, XL-1-D, and XMRS-1-D were isolated and purified from the hadal bacterium Psychrobacter pulmonis by column chromatography. The structural features of these fractions were characterized by molecular weight, monosaccharide composition, Fourier transform infrared (FTIR) spectrum, amino acid analysis and NMR. The results showed that XL-1 and XMRS-1 were mainly composed of mannose, glucose, and glucosamine, while XL-1-D and XMRS-1-D were mainly composed of mannose. In vitro bioactivity assays demonstrated that all four fractions significantly enhanced RAW264.7 macrophage proliferation and phagocytosis, stimulated nitric oxide (NO) and reactive oxygen species (ROS) production, and induced the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and the expression of inducible nitric oxide synthase (iNOS) mRNA. Moreover, plate cloning tests, cell scratch tests, and apoptosis assays, along with RT-qPCR analysis, demonstrated that the four fractions significantly inhibited A549 cells’ proliferation. Specifically, XMRS-1 and XMRS-1-D upregulated Bax, Caspase-3, Caspase-8, and Caspase-9, while downregulating Bcl-2, suggesting transcriptional activation of apoptosis-related pathways. These results offered a reference for the further development and utilization of this hadal bacterium in the future. Full article

(This article belongs to the Special Issue Exopolysaccharide Isolated from Marine Microorganisms)

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38 pages, 2297 KB

Open AccessReview

Marine-Derived Polymers–Polysaccharides as Promising Natural Therapeutics for Atherosclerotic Cardiovascular Disease

by Edmond Leonard Jim, Edwin Leopold Jim, Reggie Surya, Happy Kurnia Permatasari and Fahrul Nurkolis

Mar. Drugs 2025, 23(8), 325; https://doi.org/10.3390/md23080325 - 12 Aug 2025

Viewed by 1142

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, driven by dyslipidemia, chronic inflammation, oxidative stress, and endothelial dysfunction. Despite widespread use of lipid-lowering and anti-inflammatory agents such as statins, residual cardiovascular risk and adverse effects underscore the need [...] Read more.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, driven by dyslipidemia, chronic inflammation, oxidative stress, and endothelial dysfunction. Despite widespread use of lipid-lowering and anti-inflammatory agents such as statins, residual cardiovascular risk and adverse effects underscore the need for novel, safe, and multi-targeted therapies. Marine-derived polysaccharides (MDPs)—including fucoidan, alginate, laminarin, carrageenan, and chitosan—exhibit a spectrum of bioactivities relevant to ASCVD pathogenesis, such as anti-inflammatory, antioxidant, lipid-modulatory, antithrombotic, and endothelial-protective effects. In this critical review, we synthesize preclinical and emerging clinical evidence on the pharmacokinetics, mechanisms of action, and therapeutic potential of these compounds. We highlight translational challenges, including structural variability, poor oral bioavailability, and limited human data, and propose strategies to overcome these barriers, such as molecular standardization, novel delivery systems, and well-designed clinical trials. MDPs represent promising natural therapeutics for ASCVD prevention and treatment, warranting further investigation in rigorous human studies. Full article

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

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16 pages, 1679 KB

Open AccessReview

Unraveling of Seaweed Bioactive Substances and Their Nutritional Regulation Functions for Poultry

by Si-Bing Li, Qing-Hua Yao, Xue-Qing Ye, Balamuralikrishnan Balasubramanian and Wen-Chao Liu

Mar. Drugs 2025, 23(8), 324; https://doi.org/10.3390/md23080324 - 10 Aug 2025

Viewed by 913

Abstract

Seaweed is a rich and valuable marine biological resource that contains various bioactive substances, including polysaccharides, polyphenols, fatty acids, and more. These compounds exhibit a range of biological activities, such as antimicrobial, antioxidant, and immunomodulation effects. In the face of challenges related to [...] Read more.

Seaweed is a rich and valuable marine biological resource that contains various bioactive substances, including polysaccharides, polyphenols, fatty acids, and more. These compounds exhibit a range of biological activities, such as antimicrobial, antioxidant, and immunomodulation effects. In the face of challenges related to intensive farming, poultry are often exposed to multiple stressors during production, which can lead to oxidative stress, impaired intestinal barrier function, and excessive inflammatory responses. Due to their potent biological activities, seaweeds and their bioactive components have shown potential in improving poultry health and performance. This paper mainly reviews the classification of seaweeds and their extracts, their main biological functions, and the research progress on the application to poultry, with the aim of providing a reference for the research and application of seaweed active substances as functional feed additives in poultry. Full article

(This article belongs to the Special Issue Nutritional Content, Biologically Active Compounds, and Correlated Health Impacts of Seaweed as a Resource for Nutraceutical, Cosmetic, and Pharmaceutical Applications)

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26 pages, 8682 KB

Open AccessArticle

Hybrid Alginate–Graphene Composites: Biochemical Features and Biomedical Potential

by Marcin H. Kudzin, Anna Kaczmarek, Zdzisława Mrozińska, Cesar Hernandez, Klaudia Piekarska, Katarzyna Woźniak, Michał Juszczak and Paulina Król

Mar. Drugs 2025, 23(8), 323; https://doi.org/10.3390/md23080323 - 9 Aug 2025

Viewed by 936

Abstract

Alginate-based materials are widely studied for biomedical use, but their limited mechanical properties and variable biocompatibility pose challenges. In this work, hybrid composites composed of alginate, calcium, and graphene oxide were fabricated using a freeze-drying method and cross-linked with calcium ions via calcium [...] Read more.

Alginate-based materials are widely studied for biomedical use, but their limited mechanical properties and variable biocompatibility pose challenges. In this work, hybrid composites composed of alginate, calcium, and graphene oxide were fabricated using a freeze-drying method and cross-linked with calcium ions via calcium chloride at different concentrations. Structural and morphological features were assessed using SEM, EDS, ICP-MS, and BET analysis. The resulting composites exhibited a porous architecture, with calcium incorporation confirmed by elemental analysis. Surface characteristics and pore parameters were influenced by the presence of graphene oxide and the cross-linking process. The effects of the materials on haemostasis were evaluated through activated partial thromboplastin time (aPTT) and prothrombin time (PT) assays, revealing modulation of the intrinsic coagulation pathway without significant changes in the extrinsic pathway. In this study, we analysed the effect of alginate–graphene oxide composites on the viability of peripheral blood mononuclear (PBM) cells and human foreskin fibroblasts from the Hs68 cell line. We also assessed the genotoxic potential of alginate–graphene oxide composites on these cells. Our results showed no cyto- or genotoxic effects of the material on either cell type. These findings suggest the biocompatibility and safe character of alginate–graphene oxide composites for use with blood and skin cells. Full article

(This article belongs to the Section Biomaterials of Marine Origin)

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26 pages, 3575 KB

Open AccessArticle

Antioxidant Power of Brown Algae: Ascophyllum nodosum and Fucus vesiculosus Extracts Mitigate Oxidative Stress In Vitro and In Vivo

by Lea Karlsberger, Georg Sandner, Lenka Molčanová, Tomáš Rýpar, Stéphanie Ladirat and Julian Weghuber

Mar. Drugs 2025, 23(8), 322; https://doi.org/10.3390/md23080322 - 6 Aug 2025

Viewed by 1251

Abstract

Brown algae such as Ascophyllum nodosum (AN) and Fucus vesiculosus (FV) are gaining considerable attention as functional feed additives due to their health-beneficial properties. This study evaluated the antioxidant potential of AN and FV extracts in intestinal epithelial cells and the in vivo [...] Read more.

Brown algae such as Ascophyllum nodosum (AN) and Fucus vesiculosus (FV) are gaining considerable attention as functional feed additives due to their health-beneficial properties. This study evaluated the antioxidant potential of AN and FV extracts in intestinal epithelial cells and the in vivo model Caenorhabditis elegans (C. elegans). Aqueous AN and FV extracts were characterized for total phenolic content (TPC), antioxidant capacity (TEAC, FRAP), and phlorotannin composition using LC-HRMS/MS. Antioxidant effects were assessed in vitro, measuring AAPH-induced ROS production in Caco-2 and IPEC-J2 cells via H₂DCF-DA, and in vivo, evaluating the effects of paraquat-induced oxidative stress and AN or FV treatment on worm motility, GST-4::GFP reporter expression, and gene expression in C. elegans. FV exhibited higher total phenolic content, antioxidant capacity (TEAC, FRAP), and a broader phlorotannin profile (degree of polymerization [DP] 2–9) than AN (DP 2–7), as determined by LC-HRMS/MS. Both extracts attenuated AAPH-induced oxidative stress in epithelial cells, with FV showing greater efficacy. In C. elegans, pre-treatment with AN and FV significantly mitigated a paraquat-induced motility decline by 22% and 11%, respectively, compared to PQ-stressed controls. Under unstressed conditions, both extracts enhanced nematode healthspan, with significant effects observed at 400 µg/g for AN and starting at 100 µg/g for FV. Gene expression analysis indicated that both extracts modulated antioxidant pathways in unstressed worms. Under oxidative stress, pre-treatment with AN and FV significantly reduced GST-4::GFP expression. In the nematode, AN was more protective under acute stress, whereas FV better supported physiological function in the absence of stressors. These findings demonstrate that AN and FV counteract oxidative stress in intestinal epithelial cells and in C. elegans, highlighting their potential as stress-reducing agents in animal feed. Full article

(This article belongs to the Special Issue Marine Algae Benefits in Pharmaceuticals, Cosmeceuticals, and Nutraceuticals)

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38 pages, 9437 KB

Open AccessReview

Antibacterial Polysaccharides in Dental Implantology

by Lubica Hallmann and Mark Daniel Gerngroß

Mar. Drugs 2025, 23(8), 321; https://doi.org/10.3390/md23080321 - 4 Aug 2025

Viewed by 1106

Abstract

Background: The aim of this review is to summarize and evaluate the properties of antibacterial polysaccharides for application in dental implantology to identify knowledge gaps and provide new research ideas. Methods: The electronic databases PubMed, Medline, ProQuest, and Google Scholar were used [...] Read more.

Background: The aim of this review is to summarize and evaluate the properties of antibacterial polysaccharides for application in dental implantology to identify knowledge gaps and provide new research ideas. Methods: The electronic databases PubMed, Medline, ProQuest, and Google Scholar were used to search for peer-reviewed scientific publications published between 2018 and 2025 that provide insights to answer research questions on the role of antibacterial polysaccharides in combating pathogens in dental implantology without triggering immune reactions and inflammation. Further research questions relate to the efficacy against various dental pathogens and the understanding of the antibacterial mechanism, which may enable the development of functionalized polysaccharides with long-term antibacterial activity. Results: Biomedical implants have revolutionized medicine but also increased the risk of infections. Implant infections are a major problem in implantology and lead to implant failure and replacement. An antibacterial coating could be an excellent strategy to extend the lifespan of implants and improve the quality of the patient’s life. Bacterial resistance to antibiotics poses significant challenges for researchers, forcing them to search for new ways to prevent bacterial infections in implantology. Antibacterial natural polymers have recently received considerable research attention due to their long-term antibacterial activity. Polysaccharides from marine sources, such as chitosan and alginate, or pectin, xanthan, etc., from various plants, appear to be promising biopolymers for such applications in implantology due to their antibacterial activity, biocompatibility, and osteogenic properties. The antibacterial activity of these natural biopolymers depends on their chemical and physical properties. Nanopolysaccharides exhibit higher antibacterial activity than conventional polysaccharides, but their toxicity to human cells must be considered. Their antibacterial activity is based on the disruption of bacterial DNA or RNA synthesis, increased cell wall permeability, membrane disruption, and cytoplasmic leakage. Conclusions: Polysaccharides are a class of natural polymers with a broad spectrum of biological activities. They exhibit antioxidant, immunomodulatory, anticoagulant, anticancer, anti-inflammatory, antibacterial, and antiviral activity. Furthermore, polysaccharides are non-cytotoxic and exhibit good biocompatibility with osteogenic cells. Bactericidal polysaccharides are attractive new antibacterial materials against implant infections and open up new perspectives in implantology. Full article

(This article belongs to the Special Issue Marine Biomaterials for Dental Applications)

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23 pages, 2013 KB

Open AccessArticle

Seaweeds of the Israeli Mediterranean Sea: Nutritional and Biotechnological Potential Through Seasonal and Species Variation

by Doron Yehoshua Ashkenazi, Félix L. Figueroa, Julia Vega, Shoshana Ben-Valid, Guy Paz, Eitan Salomon, Avigdor Abelson and Álvaro Israel

Mar. Drugs 2025, 23(8), 320; https://doi.org/10.3390/md23080320 - 4 Aug 2025

Viewed by 1378

Abstract

Macroalgae (seaweeds) produce unique bioactive metabolites that have enabled their survival for millions of years, offering significant potential for human benefits. In the Israeli Mediterranean Sea, no comprehensive systematic surveys of seaweeds have been published since the 1990s, and their chemical composition remains [...] Read more.

Macroalgae (seaweeds) produce unique bioactive metabolites that have enabled their survival for millions of years, offering significant potential for human benefits. In the Israeli Mediterranean Sea, no comprehensive systematic surveys of seaweeds have been published since the 1990s, and their chemical composition remains largely unexplored. This study presents an extensive survey of intertidal seaweed communities along the shallow Israeli coastline, documenting their spatial, temporal, and biochemical diversity. Of the 320 specimens collected, 55 seaweed species were identified: 29 red (Rhodophyta), 14 brown (Phaeophyceae), and 12 green (Chlorophyta). A significant shift in species abundance was documented, with a single dominant annual bloom occurring during spring, unlike previously reported biannual blooms. Chemical analysis of the dominant species revealed significant seasonal variations in compound levels, with higher protein content in winter and increased antioxidant capacity during spring. Phenolic and natural sunscreen compounds (mycosporine-like amino acids, MAAs) showed no general seasonal trend. These findings highlight the optimal environmental conditions for seaweed growth and underscore their potential for aquaculture and biotechnology. We hypothesize that the ecologically unique conditions of the Israeli Mediterranean Sea may foster resilient seaweed species enriched with distinctive chemical properties, suitable for nutritional, health, pharmaceutical, and nutraceutical applications, particularly as climate-adaptive bioresources. Full article

(This article belongs to the Special Issue Marine Algae: Unveiling Their Nutritional, Health, and Nutraceutical Potential—2nd Edition)

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26 pages, 6743 KB

Open AccessReview

Nudibranchs as Sources of Marine Natural Products with Antitumor Activity: A Comprehensive Review

by Máximo Servillera, Mercedes Peña, Laura Cabeza, Héctor J. Pula, Jose Prados and Consolación Melguizo

Mar. Drugs 2025, 23(8), 319; https://doi.org/10.3390/md23080319 - 3 Aug 2025

Viewed by 2320

Abstract

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as [...] Read more.

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)

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20 pages, 9007 KB

Open AccessReview

Marine-Derived Collagen and Chitosan: Perspectives on Applications Using the Lens of UN SDGs and Blue Bioeconomy Strategies

by Mariana Almeida and Helena Vieira

Mar. Drugs 2025, 23(8), 318; https://doi.org/10.3390/md23080318 - 1 Aug 2025

Viewed by 1281

Abstract

Marine biomass, particularly from waste streams, by-products, underutilized, invasive, or potential cultivable marine species, offers a sustainable source of high-value biopolymers such as collagen and chitin. These macromolecules have gained significant attention due to their biocompatibility, biodegradability, functional versatility, and broad applicability across [...] Read more.

Marine biomass, particularly from waste streams, by-products, underutilized, invasive, or potential cultivable marine species, offers a sustainable source of high-value biopolymers such as collagen and chitin. These macromolecules have gained significant attention due to their biocompatibility, biodegradability, functional versatility, and broad applicability across health, food, wellness, and environmental fields. This review highlights recent advances in the uses of marine-derived collagen and chitin/chitosan. In alignment with the United Nations Sustainable Development Goals (SDGs), we analyze how these applications contribute to sustainability, particularly in SDGs related to responsible consumption and production, good health and well-being, and life below water. Furthermore, we contextualize the advancement of product development using marine collagen and chitin/chitosan within the European Union’s Blue bioeconomy strategies, highlighting trends in scientific research and technological innovation through bibliometric and patent data. Finally, the review addresses challenges facing the development of robust value chains for these marine biopolymers, including collaboration, regulatory hurdles, supply-chain constraints, policy and financial support, education and training, and the need for integrated marine resource management. The paper concludes with recommendations for fostering innovation and sustainability in the valorization of these marine resources. Full article

(This article belongs to the Special Issue Innovative Biotechnology Processes for Marine By-Products: From Waste Stream to Value Stream)

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24 pages, 1165 KB

Open AccessReview

Neoxanthin: A Promising Medicinal and Nutritional Carotenoid

by Jiarong Zhao, Gengjie Zhuang and Jinrong Zhang

Mar. Drugs 2025, 23(8), 317; https://doi.org/10.3390/md23080317 - 1 Aug 2025

Viewed by 991

Abstract

Neoxanthin is a xanthophyll carotenoid with high-value nutritional functions for human health due to its anti-cancer, anti-oxidative, and anti-obesity activities. In this present work, we systematically reviewed the structure, source, and biosynthetic pathways of neoxanthin, and discussed the advantages and disadvantages of the [...] Read more.

Neoxanthin is a xanthophyll carotenoid with high-value nutritional functions for human health due to its anti-cancer, anti-oxidative, and anti-obesity activities. In this present work, we systematically reviewed the structure, source, and biosynthetic pathways of neoxanthin, and discussed the advantages and disadvantages of the prevailing extraction methods of neoxanthin. Meanwhile, this review described the latest research progress on the pharmacological activities of neoxanthin. Finally, we concluded with a discussion on the main challenges of neoxanthin production from microalgae, and proposed some future development prospects and potential solutions. Full article

(This article belongs to the Special Issue Marine Carotenoids and Potential Therapeutic Benefits)

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10 pages, 726 KB

Open AccessArticle

Discovery of New Everninomicin Analogs from a Marine-Derived Micromonospora sp. by Metabolomics and Genomics Approaches

by Tae Hyun Lee, Nathan J. Brittin, Imraan Alas, Christopher D. Roberts, Shaurya Chanana, Doug R. Braun, Spencer S. Ericksen, Song Guo, Scott R. Rajski and Tim S. Bugni

Mar. Drugs 2025, 23(8), 316; https://doi.org/10.3390/md23080316 - 31 Jul 2025

Viewed by 838

Abstract

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal [...] Read more.

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal component analysis (hcapca) revealed that WMMD956 displayed an extreme degree of metabolomic and genomic novelty. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and Global Natural Product Social molecular networking platform (GNPS) analysis of WMMD956 resulted in the identification of several analogs of the previously known everninomicin. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, and the use of MS/MS data. The isolated metabolites, 1–3, were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Full article

(This article belongs to the Special Issue Bioactive Compounds from Challenging Marine Environments)

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35 pages, 1467 KB

Open AccessReview

Marine Derived Strategies Against Neurodegeneration

by Vasileios Toulis, Gemma Marfany and Serena Mirra

Mar. Drugs 2025, 23(8), 315; https://doi.org/10.3390/md23080315 - 31 Jul 2025

Viewed by 1369

Abstract

Marine ecosystems are characterized by an immense biodiversity and represent a rich source of biological compounds with promising potential for the development of novel therapeutic drugs. This review describes the most promising marine-derived neuroprotective compounds with strong potential for the treatment of neurodegenerative [...] Read more.

Marine ecosystems are characterized by an immense biodiversity and represent a rich source of biological compounds with promising potential for the development of novel therapeutic drugs. This review describes the most promising marine-derived neuroprotective compounds with strong potential for the treatment of neurodegenerative disorders. We focus specifically on the retina and brain—two key components of the central nervous system—as primary targets for therapeutic interventions against neurodegeneration. Alzheimer’s disease and retinal degeneration diseases are used here as a representative model of neurodegenerative disorders, where complex molecular processes such as protein misfolding, oxidative stress, and neuroinflammation drive disease progression. We also examine gene therapy approaches inspired by marine biology, with particular attention to their application in retinal diseases, aimed at preserving or restoring photoreceptor function and vision. Full article

(This article belongs to the Special Issue Marine-Derived Novel Drugs in the Treatment of Alzheimer’s Disease)

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21 pages, 879 KB

Open AccessArticle

Multiblock Metabolomics Responses of the Diatom Phaeodactylum tricornutum Under Benthic and Planktonic Culture Conditions

by Andrea Castaldi, Mohamed Nawfal Triba, Laurence Le Moyec, Cédric Hubas, Gaël Le Pennec and Marie-Lise Bourguet-Kondracki

Mar. Drugs 2025, 23(8), 314; https://doi.org/10.3390/md23080314 - 31 Jul 2025

Viewed by 1089

Abstract

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated [...] Read more.

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated on three laboratory substrates (glass, polystyrene, and polydimethylsiloxane) and under planktonic conditions. Our results revealed metabolic differences between adherent and planktonic cultures, particularly concerning the lipid and carbohydrate contents. Adherent cultures showed a metabolic profile with an increase in betaine lipids (DGTA/S), fatty acids (tetradecanoic and octadecenoic acids), and sugars (myo-inositol and ribose), suggesting modifications in membrane composition and lipid remodeling, which play a potential role in adhesion. In contrast, planktonic cultures displayed a higher content of cellobiose, specialized metabolites such as dihydroactinidiolide, quinic acid, catechol, and terpenes like phytol, confirming different membrane composition, energy storage capacity, osmoregulation, and stress adaptation. The adaptative strategies do not only concern adherent and planktonic states, but also different adherent culture conditions, with variations in lipid, amino acid, terpene, and carbohydrate contents depending on the physical properties of the support. Our results highlight the importance of metabolic adaptation in adhesion, which could explain the fouling process. Full article

(This article belongs to the Special Issue Marine Omics for Drug Discovery and Development, 2nd Edition)

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18 pages, 8458 KB

Open AccessArticle

Exploring the Biosynthetic Potential of Microorganisms from the South China Sea Cold Seep Using Culture-Dependent and Culture-Independent Approaches

by Gang-Ao Hu, Huai-Ying Sun, Qun-Jian Yin, He Wang, Shi-Yi Liu, Bin-Gui Wang, Hong Wang, Xin Li and Bin Wei

Mar. Drugs 2025, 23(8), 313; https://doi.org/10.3390/md23080313 - 30 Jul 2025

Viewed by 785

Abstract

Cold seep ecosystems harbor unique microbial communities with potential for producing secondary metabolites. However, the metabolic potential of cold seep microorganisms in the South China Sea remains under-recognized. This study employed both culture-dependent and culture-independent approaches, including 16S rRNA amplicon sequencing and metagenomics, [...] Read more.

Cold seep ecosystems harbor unique microbial communities with potential for producing secondary metabolites. However, the metabolic potential of cold seep microorganisms in the South China Sea remains under-recognized. This study employed both culture-dependent and culture-independent approaches, including 16S rRNA amplicon sequencing and metagenomics, to investigate microbial communities and their potential for secondary metabolite production in the South China Sea cold seep. The results indicate microbial composition varied little between two non-reductive sediments but differed significantly from the reductive sediment, primarily due to Planctomycetes and Actinobacteria. Predicting the Secondary Metabolism Potential using Amplicon (PSMPA) predictions revealed 115 strains encoding more than 10 biosynthetic gene clusters (BGCs), with lower BGC abundance in reductive sediment. Culture-dependent studies showed Firmicutes as the dominant cultivable phylum, with strains from shallow samples encoding fewer BGCs. Metagenomic data confirmed distinct microbial compositions and BGC distributions across sediment types, with cold seep type having a stronger influence than geographic location. Certain BGCs showed strong correlations with sediment depth, reflecting microbial adaptation to nutrient-limited environments. This study provides a comprehensive analysis of the metabolic capabilities of South China Sea cold seep microorganisms and reveals key factors influencing their secondary metabolic potential, offering valuable insights for the efficient exploration of cold seep biological resources. Full article

(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)

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12 pages, 1849 KB

Open AccessArticle

Dolabellane Diterpenoids from Soft Coral Clavularia viridis with Anti-Inflammatory Activities

by Chufan Gu, Hongli Jia, Kang Zhou, Bin Wang, Wenhan Lin and Wei Cheng

Mar. Drugs 2025, 23(8), 312; https://doi.org/10.3390/md23080312 - 30 Jul 2025

Viewed by 689

Abstract

A chemical investigation of the EtOAc fraction from soft coral Clavularia viridis resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely clavirolides W–Z (1–4), clavularols A–H (5–12), and three known analogs (13– [...] Read more.

A chemical investigation of the EtOAc fraction from soft coral Clavularia viridis resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely clavirolides W–Z (1–4), clavularols A–H (5–12), and three known analogs (13–15). Their structures were characterized by an extensive analysis of spectroscopic data, including X-ray diffraction and ECD calculations for the assignment of absolute configurations. The structures of 2 and 4–6 are feathered as peroxyl-substituted derivatives, while compounds 7–12 possess additional oxidative cyclization, including epoxide or furan that are rare in the dolabellane family. All these compounds were evaluated for activities on cytotoxic and anti-inflammatory models. Compound 10 exhibited most potential against NO production in the BV2 cell induced by LPS with an IC₅₀ value of 18.3 μM. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

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21 pages, 2015 KB

Open AccessArticle

Enhancing Fucoxanthin Pickering Emulsion Stability and Encapsulation with Seaweed Cellulose Nanofibrils Using High-Pressure Homogenization

by Ying Tuo, Mingrui Wang, Yiwei Yu, Yixiao Li, Xingyuan Hu, Long Wu, Zongpei Zhang, Hui Zhou and Xiang Li

Mar. Drugs 2025, 23(8), 311; https://doi.org/10.3390/md23080311 - 30 Jul 2025

Viewed by 827

Abstract

Poor solubility and bioavailability have limited the application of fucoxanthin in drug and functional food processing. In order to encapsulate fucoxanthin in delivery systems, in this study, cellulose was isolated from industrial brown algae residues and high-pressure homogenized into cellulose nanofibrils (CNFs). Then, [...] Read more.

Poor solubility and bioavailability have limited the application of fucoxanthin in drug and functional food processing. In order to encapsulate fucoxanthin in delivery systems, in this study, cellulose was isolated from industrial brown algae residues and high-pressure homogenized into cellulose nanofibrils (CNFs). Then, fucoxanthin was encapsulated into the Pickering emulsion stabilized by the CNFs. The effect of high-pressure homogenization on the characteristics of cellulose and the stability of fucoxanthin emulsion was evaluated. The results indicated that CNFs prepared at 105 MPa had a diameter of 87 nm and exhibited high zeta potential and thermal stability. Encapsulation efficiency peaked at 70.8% with 1.0 mg/mL fucoxanthin, and after three freeze–thaw cycles the encapsulation efficiency was higher than 60%. The DPPH scavenging activity after 12 days’ storage at 4 °C was still 42%. Furthermore, the Pickering emulsion with 1.0 mg/mL fucoxanthin showed high stability and antioxidant activity under different pH values, salinity, temperature, and UV light exposure duration. The CNFs effectively protected fucoxanthin from degradation, offering a novel delivery system for marine bioactive compounds. To the best of our knowledge, this is the first study on the fucoxanthin delivery system of Pickering emulsion stabilized by the CNFs. Such emulsion might benefit the encapsulation and release of bioactive components in marine drugs. Full article

(This article belongs to the Special Issue Marine Carotenoids: Properties, Health Benefits, and Applications)

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42 pages, 2457 KB

Open AccessReview

Therapeutic Potential of Sea Cucumber-Derived Bioactives in the Prevention and Management of Brain-Related Disorders: A Comprehensive Review

by Purnima Rani Debi, Hrishika Barua, Mirja Kaizer Ahmmed and Shuva Bhowmik

Mar. Drugs 2025, 23(8), 310; https://doi.org/10.3390/md23080310 - 30 Jul 2025

Viewed by 2018

Abstract

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being [...] Read more.

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being studied intensively for their efficacy in assessing the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors, among others. Positive results have been observed in the upregulation in the content of p-CREB, p-PL3K, BDNF, SOD, and MDA. Furthermore, the neuroprotective mechanism of the compounds against Alzheimer’s disease revealed that suppressing the phosphorylation of tau protein by the PI3K/Akt/GSK3β pathway leads to improved synaptic plasticity and reduced nerve fiber tangles. This comprehensive review explores recent findings on the therapeutic potential of sea cucumber bioactives in the treatment of brain-related disorders. Full article

(This article belongs to the Special Issue Effects of Marine Natural Products in Brain Health and Metabolic Diseases)

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18 pages, 4455 KB

Open AccessArticle

Spermine Promotes the Formation of Conchosporangia in Pyropia haitanensis Through Superoxide Anions

by Tingting Niu, Haike Qian, Lufan Cheng, Qijun Luo, Juanjuan Chen, Rui Yang, Peng Zhang, Tiegan Wang and Haimin Chen

Mar. Drugs 2025, 23(8), 309; https://doi.org/10.3390/md23080309 - 30 Jul 2025

Viewed by 1227

Abstract

The transition from conchocelis to conchosporangia in Pyropia haitanensis represents a pivotal stage in its life cycle. As a commercially vital red alga, P. haitanensis plays a dominant role in global nori production. The transition governing its sporulation efficiency is pivotal for aquaculture [...] Read more.

The transition from conchocelis to conchosporangia in Pyropia haitanensis represents a pivotal stage in its life cycle. As a commercially vital red alga, P. haitanensis plays a dominant role in global nori production. The transition governing its sporulation efficiency is pivotal for aquaculture success, yet the underlying regulatory mechanisms, especially their integration with metabolic cues such as polyamines, remain poorly understood. This study uncovered a critical role for the polyamine spermine (SPM) in promoting conchosporangial formation, mediated through the signaling activity of superoxide anions (O₂·⁻). Treatment with SPM markedly elevated O₂·⁻ levels, an effect that was effectively inhibited by the NADPH oxidase inhibitor diphenyliodonium chloride (DPI), underscoring the role of O₂·⁻ as a key signaling molecule. Transcriptomic analysis revealed that SPM enhanced photosynthesis, carbon assimilation, and respiratory metabolism, while simultaneously activating antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), to regulate hydrogen peroxide (H₂O₂) levels and maintain redox homeostasis. Furthermore, SPM upregulated genes associated with photosynthetic carbon fixation and the C₂ oxidative photorespiration pathway, supplying the energy and metabolic resources necessary for this developmental transition. These findings suggested that SPM orchestrated O₂·⁻ signaling, photosynthetic activity, and antioxidant defenses to facilitate the transition from conchocelis to conchosporangia in P. haitanensis. Full article

(This article belongs to the Section Marine Chemoecology for Drug Discovery)

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15 pages, 1527 KB

Open AccessArticle

Marine-Inspired Ovothiol Analogs Inhibit Membrane-Bound Gamma-Glutamyl-Transpeptidase and Modulate Reactive Oxygen Species and Glutathione Levels in Human Leukemic Cells

by Annalisa Zuccarotto, Maria Russo, Annamaria Di Giacomo, Alessandra Casale, Aleksandra Mitrić, Serena Leone, Gian Luigi Russo and Immacolata Castellano

Mar. Drugs 2025, 23(8), 308; https://doi.org/10.3390/md23080308 - 30 Jul 2025

Viewed by 737

Abstract

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance [...] Read more.

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors’ chemoresistance. Full article

(This article belongs to the Special Issue Marine-Derived Novel Antioxidants)

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15 pages, 3436 KB

Open AccessArticle

Mohangic Acid H and Mohangiol: New p-Aminoacetophenone Derivatives from a Mudflat-Derived Streptomyces sp.

by Juwan Son, Ju Heon Lee, Yong-Joon Cho, Kyuho Moon and Munhyung Bae

Mar. Drugs 2025, 23(8), 307; https://doi.org/10.3390/md23080307 - 30 Jul 2025

Viewed by 910

Abstract

Streptomyces sp. AWH31-250, isolated from a tidal mudflat in the Nakdong River estuary in Busan, Republic of Korea, was found to produce two novel p-aminoacetophenone derivatives, mohangic acid H (1) and mohangiol (2). Their planar structures were established [...] Read more.

Streptomyces sp. AWH31-250, isolated from a tidal mudflat in the Nakdong River estuary in Busan, Republic of Korea, was found to produce two novel p-aminoacetophenone derivatives, mohangic acid H (1) and mohangiol (2). Their planar structures were established by comprehensive 1D and 2D NMR spectroscopy, mass spectrometry, and UV analysis, possessing a shorter carbon-chain with a diene moiety, whereas known mohangic acids A–F bear a longer carbon-chain with a triene moiety. The absolute configurations of the key stereogenic centers were determined via computational DP4+ calculations and bioinformatic analysis of the ketoreductase domain sequence from the biosynthetic gene cluster. Based on the careful gene analysis along with whole-genome sequencing, the first plausible biosynthetic pathway of mohangic acids A–G and mohangiol was proposed. Mohangic acid H (1) and mohangiol (2) displayed moderate inhibitory activity against Candida albicans isocitrate lyase with IC₅₀ values of 21.37 and 21.12 µg/mL, respectively. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

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11 pages, 2255 KB

Open AccessArticle

Potential Inhibitors of Human–Naegleria fowleri Interactions: An In Vitro Extracellular Matrix-Based Model

by Javier Chao-Pellicer, Iñigo Arberas-Jiménez, Ines Sifaoui, Ana R. Díaz-Marrero, José J. Fernández, Melissa Jamerson, José E. Piñero and Jacob Lorenzo-Morales

Mar. Drugs 2025, 23(8), 306; https://doi.org/10.3390/md23080306 - 30 Jul 2025

Viewed by 850

Abstract

Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and fulminant disease that affects the central nervous system caused by the free-living amoeba Naegleria fowleri. The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success [...] Read more.

Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and fulminant disease that affects the central nervous system caused by the free-living amoeba Naegleria fowleri. The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success of the infection and could represent an interesting target to be explored in the prevention and treatment of the disease. In this work, the effect of two sesquiterpenes with proven anti-Naegleria activity on the adhesion of the parasite was evaluated using an in vitro ECM-based model, compared with the reference drugs amphotericin B and staurosporine. Both laurinterol and (+)-elatol inhibited the adhesion of the N. fowleri trophozoites to the main proteins of the ECM when treating them at different concentrations and exposure times. This work not only reinforces the therapeutic potential of laurinterol and (+)-elatol against N. fowleri infection but also introduces the application of ECM-based adhesion assays as a novel and valuable tool for screening candidate compounds that disrupt host–pathogen interactions critical to PAM pathogenesis. Full article

(This article belongs to the Special Issue Marine Antiparasitic Agents, 2nd Edition)

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13 pages, 570 KB

Open AccessReview

Examples of Underexploited Marine Organisms in Cosmeceutical Applications

by Céline Couteau and Laurence Coiffard

Mar. Drugs 2025, 23(8), 305; https://doi.org/10.3390/md23080305 - 30 Jul 2025

Viewed by 842

Abstract

A number of marine resources have been exploited for a long time. Examples include Fucus and Laminaria, from which gelling agents are extracted. Only a few hundred thousand marine species are currently known, representing a tiny fraction of the estimated total of [...] Read more.

A number of marine resources have been exploited for a long time. Examples include Fucus and Laminaria, from which gelling agents are extracted. Only a few hundred thousand marine species are currently known, representing a tiny fraction of the estimated total of between 700,000 and one million species. This opens up numerous possibilities for innovation in the cosmetics industry. In this study, we present various species that are currently under-exploited, but which could have applications in hydration and photoprotection, for example. Algae and microalgae are worthy of interest because they can be used for hydration and anti-ageing purposes. Collagen can be extracted from animal sources and used as a substitute for collagen of bovine origin. From a marketing perspective, it is possible to market it as ‘marine collagen’. However, it is imperative to emphasize the significance of ensuring the sustainability of the resource. In accordance with this imperative, algae that are capable of being cultivated are distinguished by their enhanced qualities. Full article

(This article belongs to the Section Marine-Derived Ingredients for Drugs, Cosmeceuticals and Nutraceuticals)

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19 pages, 4058 KB

Open AccessArticle

Antitumor Activity of Ruditapes philippinarum Polysaccharides Through Mitochondrial Apoptosis in Cellular and Zebrafish Models

by Mengyue Liu, Weixia Wang, Haoran Wang, Shuang Zhao, Dongli Yin, Haijun Zhang, Chunze Zou, Shengcan Zou, Jia Yu and Yuxi Wei

Mar. Drugs 2025, 23(8), 304; https://doi.org/10.3390/md23080304 - 29 Jul 2025

Viewed by 794

Abstract

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this [...] Read more.

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management. Full article

(This article belongs to the Special Issue Isolation, Identification and Applications of Marine Source Polysaccharides and Peptides—2nd Edition)

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21 pages, 576 KB

Open AccessReview

Role of Enzyme Technologies and Applied Enzymology in Valorising Seaweed Bioproducts

by Blessing Mabate, Lithalethu Mkabayi, Deandra Rochelle Goddard, Coleen Elizabeth Grobler and Brett Ivan Pletschke

Mar. Drugs 2025, 23(8), 303; https://doi.org/10.3390/md23080303 - 29 Jul 2025

Viewed by 1189

Abstract

Seaweeds, classified as non-vascular plants, have definite advantages over terrestrial plants as they grow rapidly, can be cultivated in coastal environments, and are dependable and non-endangered sources of biomass. Algal bioproducts, which include a wide range of bioactive compounds, have drawn much interest [...] Read more.

Seaweeds, classified as non-vascular plants, have definite advantages over terrestrial plants as they grow rapidly, can be cultivated in coastal environments, and are dependable and non-endangered sources of biomass. Algal bioproducts, which include a wide range of bioactive compounds, have drawn much interest because of their applications in nutraceuticals, pharmaceuticals, agriculture, and cosmetics. Particularly in the pharmaceutical and nutraceutical fields, algal bioproducts have shown tremendous activity in regulating enzymes involved in human diseases. However, the drawbacks of conventional extraction methods impede the complete exploitation of seaweed biomass. These include low efficiency, high cost, and potential harm to the environment. Enzyme technology developments in recent years present a viable way to overcome these challenges. Enzymatic processes improve product yields and reduce the environmental impact of processing, while facilitating the more effective extraction of valuable bioactive compounds as part of an integrated biorefinery approach. Enzyme-assisted biorefinery techniques can greatly advance the creation of a circular bioeconomy and increase the yield of extracted seaweed bioproducts, thus improving their value. With the potential to scale up to industrial levels, these biotechnological developments in enzymatic extraction are developing rapidly and can advance the sustainable exploitation of seaweed resources. This review emphasises the increasing importance of enzyme technologies in the seaweed biorefinery and their contribution to developing more environmentally friendly, economically feasible, and sustainable methods for valorising products derived from seaweed. In the biorefinery industry, enzyme-assisted methods have enormous potential for large-scale industrial applications with further development, opening the door to a more sustainable, circular bioeconomy. Full article

(This article belongs to the Special Issue Research on Seaweed-Degrading Enzymes)

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18 pages, 2342 KB

Open AccessArticle

Simplified, High Yielding Extraction of Xylan/Xylo-Oligosaccharides from Palmaria palmata: The Importance of the Algae Preservation Treatment

by Diogo Coelho, Diogo Félix Costa, Mário Barroca, Sara Alexandra Cunha, Maria Manuela Pintado, Helena Abreu, Margarida Martins and Tony Collins

Mar. Drugs 2025, 23(8), 302; https://doi.org/10.3390/md23080302 - 29 Jul 2025

Viewed by 663

Abstract

The complex plant cell wall heteropolysaccharide xylan, and its breakdown products xylo-oligosaccharides and xylose, are value-added compounds with a plethora of potential applications in diverse areas. They are nonetheless currently poorly exploited, with a major bottleneck being the unavailability of efficient, low-cost, high-yield [...] Read more.

The complex plant cell wall heteropolysaccharide xylan, and its breakdown products xylo-oligosaccharides and xylose, are value-added compounds with a plethora of potential applications in diverse areas. They are nonetheless currently poorly exploited, with a major bottleneck being the unavailability of efficient, low-cost, high-yield production processes. The major objective of the present study is to identify and characterise a high-yield process for the preparation of highly pure xylan/XOS products from the macroalga Palmaria palmata. Currently, most xylan is extracted from land-sourced lignocellulosic feedstocks, but we take advantage of the high xylan content, xylan aqueous solubility, lignin-free nature, weakly linked cell wall matrix, and sustainability of the macroalga to identify a simple, sustainable, high-yield, novel-xylan-structure extraction process. This is composed of five steps: alga oven drying, milling, aqueous extraction, centrifugation, and dialysis, and we show that the alga preservation step plays a critical role in component extractability, with oven drying at high temperatures, ~100 °C, enhancing the subsequent aqueous extraction process, and providing for xylan yields as high as 80% of a highly pure (~90%) xylan product. The process developed herein and the insights gained will promote a greater availability of these bioactive compounds and open up their application potential. Full article

(This article belongs to the Special Issue Eco-Friendly Extraction and Applications of Bioactive Compounds from Marine Algae)

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Mar. Drugs, Volume 23, Issue 8 (August 2025) – 38 articles

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