Marine Drugs

38 pages, 2297 KiB

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

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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18 pages, 1679 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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, 2353 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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 Staphalococcus aureus (MRSA). Full article

(This article belongs to the Special Issue Bioactive Compounds from Extreme Marine Ecosystems)

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35 pages, 1467 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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 KiB

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

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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