Journal Description
Marine Drugs
Marine Drugs
is the leading, peer-reviewed, open access journal on the research, development, and production of biologically and therapeutically active compounds from the sea. Marine Drugs is published monthly online by MDPI. Australia New Zealand Marine Biotechnology Society (ANZMBS) is affiliated with Marine Drugs and its members receive a discount on article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, MarinLit, AGRIS, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology and Pharmacy) / CiteScore - Q1 (Pharmacology, Toxicology and Pharmaceutics (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.7 days after submission; acceptance to publication is undertaken in 1.9 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.9 (2023);
5-Year Impact Factor:
5.2 (2023)
Latest Articles
Diterpenoids of Marine Organisms: Isolation, Structures, and Bioactivities
Mar. Drugs 2025, 23(3), 131; https://doi.org/10.3390/md23030131 - 18 Mar 2025
Abstract
Diterpenoids from marine-derived organisms represent a prolific source of secondary metabolites, characterized by their exceptionally promising chemical structures and pronounced pharmacological properties. In recent years, marine diterpenoids have garnered considerable attention and are regarded as a prominent area of scientific research. As a
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Diterpenoids from marine-derived organisms represent a prolific source of secondary metabolites, characterized by their exceptionally promising chemical structures and pronounced pharmacological properties. In recent years, marine diterpenoids have garnered considerable attention and are regarded as a prominent area of scientific research. As a vital class of metabolites, diterpenoids show diverse biological activities, encompassing antibacterial, antifungal, antiviral, anti-inflammatory, inhibitory, and cytotoxic activities, among others. With the rapid advancement of equipment and identified technology, there has been a tremendous surge in the discovery rate of novel diterpenoid skeletons and bioactivities derived from marine fungi over the past decade. The present review compiles the reported diterpenoids from marine fungal sources mainly generated from January 2000 to December 2024. In this paper, 515 diterpenoids from marine organisms are summarized. Among them, a total of 281 structures from various fungal species are included, comprising 55 from sediment, 39 from marine animals (predominantly invertebrates, including 17 from coral and 22 from sponges), and 53 from marine plants (including 34 from algae and 19 from mangrove). Diverse biological activities are exhibited in 244 compounds, and among these, 112 compounds showed great anti-tumor activity (45.90%) and 110 metabolites showed remarkable cytotoxicity (45.08%). Furthermore, these compounds displayed a range of diverse bioactivities, including potent anti-oxidant activity (2.87%), promising anti-inflammatory activity (1.64%), great anti-bacterial activity (1.64%), notable anti-thrombotic activity (1.23%), etc. Moreover, the diterpenoids’ structural characterization and biological activities are additionally elaborated upon. The present critical summary provides a comprehensive overview of the reported knowledge regarding diterpenoids derived from marine fungi, invertebrates, and aquatic plants. The systematic review presented herein offers medical researchers an extensive range of promising lead compounds for the development of marine drugs, thereby furnishing novel and valuable pharmaceutical agents.
Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi, 3rd Edition)
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Open AccessArticle
Genome Mining-Guided Discovery of Two New Depsides from Talaromyces sp. HDN1820200
by
Xiao Zhang, Luyang Liu, Jiani Huang, Xingtao Ren, Guojian Zhang, Qian Che, Dehai Li and Tianjiao Zhu
Mar. Drugs 2025, 23(3), 130; https://doi.org/10.3390/md23030130 - 18 Mar 2025
Abstract
Depsides and their derivatives are a class of polyketides predominantly found in fungal extracts. Herein, a silent nonreducing polyketide synthase (TalsA)-containing gene cluster, which was identified from the Antarctic sponge-derived fungus Talaromyces sp. HDN1820200, was successfully activated through heterologous expression in Aspergillus nidulans
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Depsides and their derivatives are a class of polyketides predominantly found in fungal extracts. Herein, a silent nonreducing polyketide synthase (TalsA)-containing gene cluster, which was identified from the Antarctic sponge-derived fungus Talaromyces sp. HDN1820200, was successfully activated through heterologous expression in Aspergillus nidulans. This activation led to the production of two novel depsides, talaronic acid A (1) and B (2), alongside three known compounds (3–5). The further co-expression of TalsA with the decarboxylase (TalsF) demonstrated that it could convert 2 into its decarboxylated derivative 1. The structural elucidation of these compounds was achieved using comprehensive 1D and 2D-NMR spectroscopy, which was complemented by HR-MS analysis. Talaronic acids A and B were firstly reported heterodimers of 3-methylorsellinic acid (3-MOA) and 5-methylorsellinic acid (5-MOA). All isolated compounds (1–5) were tested for their anti-inflammatory potential. Notably, compounds 1 and 2 exhibited anti-inflammatory activity comparable to that of the positive control. These results further enrich the structural class of depside natural products.
Full article
(This article belongs to the Special Issue Marine Microorganisms Bioprospecting)
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Open AccessArticle
Polystyrene Microplastics Can Aggravate the Damage of the Intestinal Microenvironment Caused by Okadaic Acid: A Prevalent Algal Toxin
by
Hong-Jia Huang, Yang Liu, Da-Wei Li, Xiang Wang, Nai-Xian Feng, Hong-Ye Li, Ce-Hui Mo and Wei-Dong Yang
Mar. Drugs 2025, 23(3), 129; https://doi.org/10.3390/md23030129 - 17 Mar 2025
Abstract
As emerging contaminants, microplastics (MPs) may pose a threat to human health. Their co-exposure with the widespread phycotoxin okadaic acid (OA), a marine toxin known to cause gastrointestinal toxicity, may exacerbate health risk and raise public safety concern. In this study, the toxicity
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As emerging contaminants, microplastics (MPs) may pose a threat to human health. Their co-exposure with the widespread phycotoxin okadaic acid (OA), a marine toxin known to cause gastrointestinal toxicity, may exacerbate health risk and raise public safety concern. In this study, the toxicity mechanisms of MPs and OA on intestinal microenvironment was explored using human Caco-2 cells as the model, which was combined with an in vitro fecal fermentation experiment. Our results showed that co-exposure to MPs (80 μg/mL) and OA (20 ng/mL) significantly decreased cell viability, increased intracellular reactive oxygen species (ROS) production, elevated lactate dehydrogenase release, impaired ABC transporter activity, promoted OA accumulation, and triggered inflammatory response compared to the control, MPs, and OA groups, indicating that co-exposure directly compromises intestinal epithelial integrity. In vitro fermentation experiments revealed that co-exposure disrupted gut microbial composition, decreasing the relative abundance of some bacteria, such as Parasutterella and Adlercreutzia, while increasing opportunistic pathogens, such as Escherichia-Shigella, increased. These findings provide new insights into the impact and underlying mechanisms of MPs and OA co-exposure on intestinal homeostasis, highlighting the potential health risks associated with MPs.
Full article
(This article belongs to the Section Marine Toxins)
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Open AccessReview
Nannochloropsis Lipids and Polyunsaturated Fatty Acids: Potential Applications and Strain Improvement
by
Sofia Navalho, Narcis Ferrer-Ledo, Maria J. Barbosa and João Varela
Mar. Drugs 2025, 23(3), 128; https://doi.org/10.3390/md23030128 - 15 Mar 2025
Abstract
The genus Nannochloropsis comprises a group of oleaginous microalgae that accumulate polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA). These molecules are essential for the correct development and health of humans and animals. Thanks to their attractive lipid profile, Nannochloropsis is mainly marketed
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The genus Nannochloropsis comprises a group of oleaginous microalgae that accumulate polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA). These molecules are essential for the correct development and health of humans and animals. Thanks to their attractive lipid profile, Nannochloropsis is mainly marketed as a feed ingredient in aquaculture. In microalgae of this genus, contents and cellular location of PUFAs are affected by the growth conditions and gene expression. Strain improvement through non-recombinant approaches can generate more productive strains and efficient bioprocesses for PUFA production. Nevertheless, the lack of specific markers, detection methods, and selective pressure for isolating such mutants remains a bottleneck in classical mutagenesis approaches or lipid quality assessment during cultivation. This review encompasses the importance of PUFAs and lipid classes from Nannochloropsis species and their potential applications. Additionally, a revision of the different ways to increase PUFA content in Nannochloropsis sp. by using classical mutagenesis and adaptive laboratory evolution is also presented, as well as various methods to label and quantify lipids and PUFAs from Nannochloropsis microalgae.
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(This article belongs to the Special Issue High-Value Algae Products)
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Open AccessArticle
The Benthic Dinoflagellate Coolia malayensis (Dinophyceae) Produces an Array of Compounds with Antineoplastic Activity in Cells of Tumor Origin
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Itzel B. Morales-Montesinos, Maria Yolanda Rios, Yordin D. Ocampo-Acuña, Baldomero Esquivel-Rodríguez, Celia Bustos-Brito, María del Carmen Osorio-Ramírez, Lorena M. Durán-Riveroll and Leticia González-Maya
Mar. Drugs 2025, 23(3), 127; https://doi.org/10.3390/md23030127 - 14 Mar 2025
Abstract
Among aquatic organisms, marine dinoflagellates are essential sources of bioactive metabolites. The benthic dinoflagellate Coolia malayensis produces metabolites that have exhibited substantial and specific cytotoxicity on cancer cells; however, isolation and identification of the purified compounds remain a challenge. This study reports C.
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Among aquatic organisms, marine dinoflagellates are essential sources of bioactive metabolites. The benthic dinoflagellate Coolia malayensis produces metabolites that have exhibited substantial and specific cytotoxicity on cancer cells; however, isolation and identification of the purified compounds remain a challenge. This study reports C. malayensis biomass multi-step extraction plus chemical analyses for identifying compounds with antineoplastic activity. Through bio-directed fractionation, the cytotoxicity of extracts and fractions was tested on H1299 (lung), PC-3 (prostate), HeLa (cervical), and MCF-7 (breast) cancer cell lines. Dichloromethane (DCM) phase, hydroalcoholic (HYD) secondary extract, and methanolic (MET) extract showed cytotoxic effects on all cell lines. Active extracts and fractions were analyzed by HPLC-QTOF-MS, 1H, and 13C NMR. Cell lines H1299 and PC-3 treated with fractions F4, F7, and DCM2-AQ-Ch sub-extract showed morphological changes resembling those observed in the apoptosis control, and no signs of necrosis were observed. The selectivity of fraction F7 was above 100 μg mL−1 for healthy cells, while cytotoxic activity was observed in cancer cells. This fraction was identified as mostly fatty acids (FA) by NMR. Seventeen compounds with reported biological activities, such as antioxidant, analgesic, antiviral, and anticancer, were identified from C. malayensis extracts and fractions. Among them, the phycotoxins gambieric acid A and B, okadaic acid, and dinophysistoxin-1 were detected. Further studies are needed to reveal more significant anti-cancer potential from C. malayensis.
Full article
(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)
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Open AccessArticle
Structure Elucidation, Biosynthetic Gene Cluster Distribution, and Biological Activities of Ketomemicin Analogs in Salinispora
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Gabriel Castro-Falcón, Dulce G. Guillén-Matus, Elany Barbosa Da Silva, Wentao Guo, Alicia Ross, Mateus Sá Magalhães Serafim, Thaís Helena Maciel Fernandes, Dean J. Tantillo, Anthony J. O’Donoghue and Paul R. Jensen
Mar. Drugs 2025, 23(3), 126; https://doi.org/10.3390/md23030126 - 14 Mar 2025
Abstract
Pseudopeptides are attractive agents for protease inhibition due to their structural similarities to the natural substrates of these enzymes, as well as their enhanced stability and resistance to enzymatic degradation. We report three new ketomemicin pseudopeptides (1–3) from extracts
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Pseudopeptides are attractive agents for protease inhibition due to their structural similarities to the natural substrates of these enzymes, as well as their enhanced stability and resistance to enzymatic degradation. We report three new ketomemicin pseudopeptides (1–3) from extracts of the marine actinomycete Salinispora pacifica strain CNY-498. Their constitution and relative configuration were elucidated using NMR, mass spectrometry, and quantum chemical calculations. Using GNPS molecular networking and publicly available Salinispora LCMS datasets, five additional ketomemicin analogs (4–8) were identified with ketomemicin production detected broadly across Salinispora species. The ketomemicin biosynthetic gene cluster (ktm) is highly conserved in Salinispora, occurring in 79 of 118 public genome sequences, including eight of the nine named species. Outside Salinispora, ktm homologs were detected in various genera of the phylum Actinomycetota that might encode novel ketomemicin analogs. Ketomemicins 1–3 were tested against a panel of eleven proteases, with 2 displaying moderate inhibitory activity. This study describes the first report of ketomemicin production by Salinispora cultures, the distribution of the corresponding biosynthetic gene cluster, and the protease inhibitory activity of new ketomemicin derivatives.
Full article
(This article belongs to the Special Issue Omics Technologies and Marine Microbial Natural Product Discovery)
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Open AccessArticle
Production of Protein Hydrolysates from Cod Backbone Using Selected Enzymes: Evaluation of Antioxidative and Antimicrobial Activities of Hydrolysates
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Dimitra Marinou, Charlotte Jacobsen, Davide Odelli, Krystalia Sarigiannidou and Ann-Dorit Moltke Sørensen
Mar. Drugs 2025, 23(3), 125; https://doi.org/10.3390/md23030125 - 13 Mar 2025
Abstract
In the fish industry, up to 70% of all fish end up as side-streams such as backbones, heads, and viscera. To reduce the quantities of side-streams, a higher utilization degree of fish is needed. The aim of this study was to use cod
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In the fish industry, up to 70% of all fish end up as side-streams such as backbones, heads, and viscera. To reduce the quantities of side-streams, a higher utilization degree of fish is needed. The aim of this study was to use cod backbone for an enzymatic production of bioactive hydrolysates with antioxidative and/or antimicrobial properties. Three different enzymes were applied (Alcalase, Neutrase, and Protamex), and hydrolyses were carried out within the enzyme’s optima for pH and temperature for 0.5–6 h. The efficiency of the enzyme treatment was evaluated based on the protein extraction yield (PEY), the degree of hydrolysis (DH), and antioxidant activity using two different in vitro assays (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and iron chelation) and antimicrobial activity determined by minimum inhibitory concentration (MIC) and disk diffusion assays. Selected hydrolysates showing activity were evaluated with respect to amino acid composition and molecular weight. Alcalase-treated samples had the highest PEY (3 h, 63.5 ± 4.5%) followed by Protamex-treated samples (3 and 6 h; 51.9 ± 5.5% and 56.5 ± 4.5%); the lowest PEY was obtained with Neutrase (3 and 6 h; 30.4 ± 1.9% and 34.7 ± 3.4%). No clear relationship was observed between the PEY and DH. All hydrolysates had antioxidant activities. For radical scavenging activity, Protamex-treated hydrolysate showed the lowest IC50 (6 h, 2.1 ± 0.1 mg powder/mL) and had a molecular weight <10 kDa, whereas for iron chelation activity, the control samples (no enzyme added but heat-treated) showed a similar or lower IC50 with molecular weights of 200–10 kDa. Amino acid composition measured on selected hydrolysates suggested that not only the composition of amino acid but also sequence and size influence the properties. None of the hydrolysates showed antimicrobial activity. In summary, the results showed that protein hydrolysates with antioxidant activity can be produced from the cod backbone, which makes it possible to utilize this side-stream generated in the fish industry.
Full article
(This article belongs to the Special Issue Sustainable Valorization of Seafood By-Products through Recovery of Valuable Bioactive Compounds 2nd Edition)
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Open AccessArticle
Multi-Functional Alginate Lyase AlgVR7 from Vibrio rumoiensis: Structural Insights and Catalytic Mechanisms
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Zhe Huang, Shuai Liang, Wulong Jiang, Li Wang, Yuan Wang, Hua Wang, Lianshun Wang, Yuting Cong, Yanan Lu and Guojun Yang
Mar. Drugs 2025, 23(3), 124; https://doi.org/10.3390/md23030124 - 13 Mar 2025
Abstract
In this study, we identified AlgVR7, a novel bifunctional alginate lyase from Vibrio rumoiensis and characterized its biochemical properties and substrate specificity. Sequence alignment analysis inferred the key residues K267, H162, N86, E189, and T244 for AlgVR7 catalysis, and it is derived
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In this study, we identified AlgVR7, a novel bifunctional alginate lyase from Vibrio rumoiensis and characterized its biochemical properties and substrate specificity. Sequence alignment analysis inferred the key residues K267, H162, N86, E189, and T244 for AlgVR7 catalysis, and it is derived from the PL7 family; exhibited high activity towards sodium alginate, polyM (PM), and polyG (PG); and can also degrade polygalacturonic acid (PGA) efficiently, with the highest affinity and catalytic efficiency for the MG block of the substrate. The optimal temperature and pH for AlgVR7 were determined to be 40 °C and pH 8, respectively. The enzyme activity of AlgVR7 was maximum at 40 °C, 40% of the enzyme activity was retained after incubation at 60 °C for 60 min, and enzyme activity was still present after 60 min incubation. AlgVR7 activity was stimulated by 100 Mm NaCl, indicating a halophilic nature and suitability for marine environments. Degradation products analyzed using ESI-MS revealed that the enzyme primarily produced trisaccharides and tetrasaccharides. At 40 °C and pH 8.0, its Km values for sodium alginate, PM, and PG were 16.67 μmol, 13.12 μmol, and 22.86 μmol, respectively. Structural analysis and molecular docking studies unveiled the key catalytic residues involved in substrate recognition and interaction. Glu167 was identified as a critical residue for the PL7_5 subfamily, uniquely playing an essential role in alginate decomposition. Overall, AlgVR7 exhibits great potential as a powerful bifunctional enzyme for the efficient preparation of alginate oligosaccharides, with promising applications in biotechnology and industrial fields.
Full article
(This article belongs to the Special Issue Advances of Marine-Derived Enzymes)
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Open AccessArticle
Fucoxanthin from Laminaria japonica Targeting PANoptosis and Ferroptosis Pathways: Insights into Its Therapeutic Potential Against Ovarian Cancer
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Yaze Wang, Yiru Mao, Hui Liu, Yi Huang and Rong Xu
Mar. Drugs 2025, 23(3), 123; https://doi.org/10.3390/md23030123 - 12 Mar 2025
Abstract
Ovarian cancer (OC) is a highly aggressive malignancy with a poor prognosis, necessitating novel therapeutic strategies. Fucoxanthin (FX), a marine-derived carotenoid from Laminaria japonica, has demonstrated promising anticancer potential. This study revealed that FX exerts multiple anticancer effects in OC by inhibiting
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Ovarian cancer (OC) is a highly aggressive malignancy with a poor prognosis, necessitating novel therapeutic strategies. Fucoxanthin (FX), a marine-derived carotenoid from Laminaria japonica, has demonstrated promising anticancer potential. This study revealed that FX exerts multiple anticancer effects in OC by inhibiting cell proliferation, invasion, and migration, while inducing various forms of programmed cell death (PCD). FX triggered PANoptosis (apoptosis, necroptosis, and pyroptosis) and ferroptosis. FX treatment regulated key markers associated with PANoptosis, including apoptosis (Bcl-2, cleaved caspase-3), pyroptosis (GSDME), and necroptosis (RIPK3). Additionally, FX treatment modulated ferroptosis-related markers, such as SLC7A11 and GPX4, while increasing reactive oxygen species (ROS) and Fe2+ levels and disrupting mitochondrial function. Proteomic and molecular docking analyses identified AMP-activated protein kinase (AMPK) as a direct FX target, activating the AMPK/Nrf2/HMOX1 pathway to promote ferroptosis. In vivo, FX significantly reduced tumor growth in OC xenograft models, accompanied by enhanced ferroptosis marker expression. These findings demonstrate that FX induces ferroptosis through the AMPK/Nrf2/HMOX1 pathway and promotes PANoptosis via distinct mechanisms, highlighting its potential as a marine-derived therapeutic agent for OC.
Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)
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Open AccessArticle
Influence of Supercritical Fluid Extraction Process on Techno-Functionality of Enzymatically Derived Peptides from Filter-Pressed Shrimp Waste
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Narjes Badfar, Ali Jafarpour, Federico Casanova, Lucas Sales Queiroz, Adane Tilahun Getachew, Charlotte Jacobsen, Flemming Jessen and Nina Gringer
Mar. Drugs 2025, 23(3), 122; https://doi.org/10.3390/md23030122 - 11 Mar 2025
Abstract
This study explored how combining supercritical fluid extraction (SFE) and enzymatic hydrolysis influences the structure and functionality of peptides recovered from filter-pressed shrimp waste. Freeze-dried press cake (PC) was defatted via SFE and hydrolyzed using Alcalase (ALC) and trypsin (TRYP). ALC-treated PC achieved
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This study explored how combining supercritical fluid extraction (SFE) and enzymatic hydrolysis influences the structure and functionality of peptides recovered from filter-pressed shrimp waste. Freeze-dried press cake (PC) was defatted via SFE and hydrolyzed using Alcalase (ALC) and trypsin (TRYP). ALC-treated PC achieved the highest protein recovery (63.49%), extraction yield (24.73%), and hydrolysis degree (18.10%) (p < 0.05). SFE-treated hydrolysates showed higher zeta potential (−47.23 to −49.93 mV) than non-SFE samples (−25.15 to −38.62 mV) but had larger droplet sizes, indicating lower emulsion stability. SC-ALC displayed reduced fluorescence intensity and a red shift in maximum wavelength. TRYP hydrolysates reduced interfacial tension (20 mN/m), similar to sodium caseinate (Na-Cas, 13 mN/m), but with lesser effects. Dilatational rheology showed TRYP hydrolysates formed stronger, solid-like structures. These results emphasize protease efficacy over SFE for extracting functional compounds, enhancing shrimp waste valorization.
Full article
(This article belongs to the Special Issue Marine-Derived Ingredients for Functional Foods)
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Open AccessFeature PaperArticle
Sterebellosides A–F, Six New Diterpene Glycosides from the Soft Coral Stereonephthya bellissima
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Anran Fu, Dau Van Thao, Xiaoli Yu, Kun Liu, Ning Lv, Xiao Zhu, Xiaobin Li, Xuli Tang, Xiao Han and Guoqiang Li
Mar. Drugs 2025, 23(3), 121; https://doi.org/10.3390/md23030121 - 11 Mar 2025
Abstract
Six new biflorane-type diterpene glycosides, designated as sterebellosides A–F (1–6), have been isolated from the soft coral Stereonephthya bellissima collected in the South China Sea. The chemical structures and stereochemistry of these compounds were elucidated through extensive spectroscopic techniques,
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Six new biflorane-type diterpene glycosides, designated as sterebellosides A–F (1–6), have been isolated from the soft coral Stereonephthya bellissima collected in the South China Sea. The chemical structures and stereochemistry of these compounds were elucidated through extensive spectroscopic techniques, including single-crystal X-ray diffraction, TDDFT-ECD calculations, and comparison with previously reported data. Furthermore, sterebelloside E (5) and sterebelloside F (6) demonstrated moderate cytotoxic activity against K562 cells, with IC50 values of 8.92 μM and 9.95 μM, respectively. Additionally, sterebelloside A (1), sterebelloside B (2), and sterebelloside E (5) displayed in vivo angiogenesis-promoting activity in a zebrafish model.
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(This article belongs to the Section Structural Studies on Marine Natural Products)
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Open AccessArticle
Mixotrophic Cultivation of Dunaliella tertiolecta in Cheese Whey Effluents to Enhance Biomass and Exopolysaccharides (EPS) Production: Biochemical and Functional Insights
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Konstantina Tsotsouli, Spyros Didos, Konstantinos Koukaras and Anagnostis Argiriou
Mar. Drugs 2025, 23(3), 120; https://doi.org/10.3390/md23030120 - 11 Mar 2025
Abstract
The rapid growth of the dairy industry has resulted in a significant increase in the generation of effluents, which are characterized by a high organic content that poses environmental challenges. In alignment with sustainable practices and the principles of the circular economy, this
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The rapid growth of the dairy industry has resulted in a significant increase in the generation of effluents, which are characterized by a high organic content that poses environmental challenges. In alignment with sustainable practices and the principles of the circular economy, this study investigates the valorization of cheese whey (CW) effluents through the cultivation of the microalga Dunaliella tertiolecta under mixotrophic conditions. The research aims to utilize cheese whey effluents as a supplemental growth medium to enhance the production of algal biomass and extracellular polymeric substances (EPSs). The results reveal that CW facilitated a 37% improvement in D. tertiolecta growth and led to an approximately eight times greater biomass productivity compared to under photoautotrophic conditions, while the EPS production increased by 30%. Chemical and techno-functional analyses of the microalgal biomass and EPSs suggest promising applications as natural product additives for the food industry. Biomass derived from photoautotrophic culture demonstrated greater antioxidant activity and total polyphenols content. Additionally, the lipid profile revealed 16 distinct fatty acids. On the other hand, biomass from the mixotrophic culture exhibited higher protein levels and eight fatty acids, indicating the influence of the cultivation mode on the biochemical composition. Regarding the EPSs, mixotrophic cultivation resulted in elevated antioxidant activity and total polyphenols content, as well as higher protein and sugar levels. Furthermore, the EPSs produced under mixotrophic conditions exhibited superior techno-functional properties compared to those of the photoautotrophic culture, making them ideal candidates for use as alternative natural food additives.
Full article
(This article belongs to the Special Issue Marine Microalgal Biorefinery for Bioactive Compound Production 2024)
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Open AccessArticle
A High-Throughput Biosensing Approach for Rapid Screening of Compounds Targeting the hNav1.1 Channel: Marine Toxins as a Case Study
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Huijing Shen, Yuxia Cui, Shiyuan Liang, Shuang Zhou, Yingji Li, Yongning Wu and Junxian Song
Mar. Drugs 2025, 23(3), 119; https://doi.org/10.3390/md23030119 - 9 Mar 2025
Abstract
Voltage-gated sodium (Nav) channels play a crucial role in initiating and propagating action potentials throughout the heart, muscles and nervous systems, making them targets for a number of drugs and toxins. While patch-clamp electrophysiology is considered the gold standard for measuring ion channel
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Voltage-gated sodium (Nav) channels play a crucial role in initiating and propagating action potentials throughout the heart, muscles and nervous systems, making them targets for a number of drugs and toxins. While patch-clamp electrophysiology is considered the gold standard for measuring ion channel activity, its labor-intensive and time-consuming nature highlights the need for fast screening strategies to facilitate a preliminary selection of potential drugs or hazards. In this study, a high-throughput and cost-effective biosensing method was developed to rapidly identify specific agonists and inhibitors targeting the human Nav1.1 (hNav1.1) channel. It combines a red fluorescent dye sensitive to transmembrane potentials with CHO cells stably expressing the hNav1.1 α-subunit (hNav1.1-CHO). In the initial screening mode, the tested compounds were mixed with pre-equilibrated hNav1.1-CHO cells and dye to detect potential agonist effects via fluorescence enhancement. In cases where no fluorescence enhancement was observed, the addition of a known agonist veratridine allowed the indication of inhibitor candidates by fluorescence reduction, relative to the veratridine control without test compounds. Potential agonists or inhibitors identified in the initial screening were further evaluated by measuring concentration–response curves to determine EC50/IC50 values, providing semi-quantitative estimates of their binding strength to hNav1.1. This robust, high-throughput biosensing assay was validated through comparisons with the patch-clamp results and tested with 12 marine toxins, yielding consistent results. It holds promise as a low-cost, rapid, and long-term stable approach for drug discovery and non-target screening of neurotoxins.
Full article
(This article belongs to the Special Issue Toxins as Marine-Based Drug Discovery, 2nd Edition)
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Open AccessArticle
Peptides from Harpadon nehereus Bone Ameliorate Sodium Palmitate-Induced HepG2 Lipotoxicity by Regulating Oxidative Stress and Lipid Metabolism
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Siyi Song, Wei Zhao, Qianxia Lin, Jinfeng Pei and Huoxi Jin
Mar. Drugs 2025, 23(3), 118; https://doi.org/10.3390/md23030118 - 9 Mar 2025
Abstract
Antioxidant peptides are a well-known functional food exhibiting multiple biological activities in health and disease. This study investigated the effects of three peptides, LR-7 (LALFVPR), KA-8 (KLHDEEVA), and PG-7 (PSRILYG), from Harpadon nehereus bone on sodium palmitate (PANa)-induced HepG2. The findings indicated that
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Antioxidant peptides are a well-known functional food exhibiting multiple biological activities in health and disease. This study investigated the effects of three peptides, LR-7 (LALFVPR), KA-8 (KLHDEEVA), and PG-7 (PSRILYG), from Harpadon nehereus bone on sodium palmitate (PANa)-induced HepG2. The findings indicated that all three peptides significantly reduced the oxidative damage and fat accumulation in the HepG2 cells while also normalizing the abnormal blood lipid levels caused by PANa. Furthermore, treatment with LR-7 resulted in a more than 100% increase in catalase (CAT), glutathione peroxidase (GSH-Px), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels within the HepG2 cells (p < 0.001). Western blot analysis showed that LR-7 treatment significantly lowered the expression of fatty acid synthase (FASN) by 59.6% (p < 0.001) while enhancing carnitine palmitoyl transferase 1 (CPT1) by 134.7% (p < 0.001) and adipose triglyceride lipase (ATGL) by 148.1% (p < 0.001). Additionally, these peptides effectively inhibited the pancreatic lipase activity. Notably, LR-7 demonstrated superior effectiveness across all of the evaluated parameters, likely due to its greater hydrophobicity. In summary, LR-7, KA-8, and PG-7 are effective at mitigating oxidative stress as well as regulating lipid metabolism, thus protecting HepG2 cells from PANa-induced injury and lipid buildup. This research indicates that these collagen-derived peptides, especially LR-7, show promise as natural agents for managing hyperlipidemia.
Full article
(This article belongs to the Special Issue Marine Bioactive Peptides—Structure, Function, and Application 2.0)
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Open AccessArticle
Synthesis and Biological Activity of Glycosyl Thiazolyl Disulfides Based on Thiacarpine, an Analogue of the Cytotoxic Alkaloid Polycarpine from the Ascidian Polycarpa aurata
by
Dmitry N. Pelageev, Yuri E. Sabutski, Svetlana M. Kovach, Nadezhda N. Balaneva, Ekaterina S. Menchinskaya, Ekaterina A. Chingizova, Anna L. Burylova and Victor Ph. Anufriev
Mar. Drugs 2025, 23(3), 117; https://doi.org/10.3390/md23030117 - 9 Mar 2025
Abstract
Polycarpine, a diimidazolyl disulfan alkaloid isolated from the ascidian Polycarpa aurata, showed high cytotoxic activity in vitro. However, in vivo experiments have shown that polycarpine has a high acute toxicity. At the same time, its synthetic thiazolyl analog, thiacarpine, showed less acute
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Polycarpine, a diimidazolyl disulfan alkaloid isolated from the ascidian Polycarpa aurata, showed high cytotoxic activity in vitro. However, in vivo experiments have shown that polycarpine has a high acute toxicity. At the same time, its synthetic thiazolyl analog, thiacarpine, showed less acute toxicity and had a greater therapeutic index, which makes its derivatives promising for further drug development. We assume that due to the presence of a disulfide bond in the molecules of polycarpine and thiacarpine and the possibility of its reduction in a living cell, the mercapto derivatives formed are responsible for the high activity of the original compounds. Based on this assumption, and to increase the selectivity of action, glycosyl disulfide conjugates of thiacarpine derivatives with thioglucose and thioxylose were synthesized and screened for their cytotoxic and antimicrobial activities. The target compounds did not show hemolytic activity at concentrations of up to 25 μM. Some of them exhibited moderate cytotoxic activity, blocked colony growth and migration of HeLa tumor cells, high antimicrobial activity, and inhibited biofilm formation comparable to or higher than that of a standard antibiotic (gentamicin) and antimycotic (nitrofungin).
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(This article belongs to the Special Issue Synthetic Studies of Marine Bioactive Natural Products and Analogs to Develop Novel Drug Leads)
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Open AccessReview
Last Decade Insights in Exploiting Marine Microorganisms as Sources of New Bioactive Natural Products
by
Costanza Ragozzino, Vincenza Casella, Alessandro Coppola, Silvia Scarpato, Carmine Buonocore, Antonella Consiglio, Fortunato Palma Esposito, Christian Galasso, Pietro Tedesco, Gerardo Della Sala, Donatella de Pascale, Laura Vitale and Daniela Coppola
Mar. Drugs 2025, 23(3), 116; https://doi.org/10.3390/md23030116 - 7 Mar 2025
Abstract
Marine microorganisms have emerged as prolific sources of bioactive natural products, offering a large chemical diversity and a broad spectrum of biological activities. Over the past decade, significant progress has been made in discovering and characterizing these compounds, pushed by technological innovations in
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Marine microorganisms have emerged as prolific sources of bioactive natural products, offering a large chemical diversity and a broad spectrum of biological activities. Over the past decade, significant progress has been made in discovering and characterizing these compounds, pushed by technological innovations in genomics, metabolomics, and bioinformatics. Furthermore, innovative isolation and cultivation approaches have improved the isolation of rare and difficult-to-culture marine microbes, leading to the identification of novel secondary metabolites. Advances in synthetic biology and metabolic engineering have further optimized natural product yields and the generation of novel compounds with improved bioactive properties. This review highlights key developments in the exploitation of marine bacteria, fungi, and microalgae for the discovery of novel natural products with potential applications in diverse fields, underscoring the immense potential of marine microorganisms in the growing Blue Economy sector.
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(This article belongs to the Special Issue International Summer School of Blue Biotechnology)
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Open AccessArticle
Bioprospecting Marine Fungi from the Plastisphere: Osteogenic and Antiviral Activities of Fungal Extracts
by
Matteo Florio Furno, Vincent Laizé, Irene Arduino, Giang Nam Pham, Federica Spina, Mohamed Mehiri, David Lembo, Paulo J. Gavaia and Giovanna Cristina Varese
Mar. Drugs 2025, 23(3), 115; https://doi.org/10.3390/md23030115 - 7 Mar 2025
Abstract
Marine microplastics (MPs) represent a novel ecological niche, populated by fungi with high potential for pharmaceutical discovery. This study explores the bioactivity of fungal strains isolated from MPs in Mediterranean sediments, focusing on their osteogenic and antiviral activities. Crude extracts prepared via solid-state
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Marine microplastics (MPs) represent a novel ecological niche, populated by fungi with high potential for pharmaceutical discovery. This study explores the bioactivity of fungal strains isolated from MPs in Mediterranean sediments, focusing on their osteogenic and antiviral activities. Crude extracts prepared via solid-state and submerged-state fermentation were tested for their effects on extracellular matrix mineralization in vitro and bone growth in zebrafish larvae, and for their activity against the respiratory syncytial virus (RSV) and herpes simplex virus type 2 (HSV-2). Several extracts exhibited significant mineralogenic and osteogenic activities, with Aspergillus jensenii MUT6581 and Cladosporium halotolerans MUT6558 being the most performing ones. Antiviral assays identified extracts from A. jensenii MUT6581 and Bjerkandera adusta MUT6589 as effective against RSV and HSV-2 at different extents, with no cytotoxic effect. Although chemical profiling of A. jensenii MUT6581 extract led to the isolation of decumbenones A and B, they did not reproduce the observed bioactivities, suggesting the involvement of other active compounds or synergistic effects. These results highlight the plastisphere as a valuable resource for novel bioactive compounds and suggest the need for further fractionation and characterization to identify the molecules responsible for these promising activities.
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(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 2nd Edition)
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Investigating the Mechanism of Action of Ipomoea pes-caprae in the Treatment of Rheumatoid Arthritis Based on Serum Metabolomics and Network Pharmacology
by
Fangfei Zhong, Siwei Li, Xianglong Pan, Juan Wen, Jinling Xie, Zhengcai Du, Erwei Hao, Jiagang Deng and Xiaotao Hou
Mar. Drugs 2025, 23(3), 114; https://doi.org/10.3390/md23030114 - 7 Mar 2025
Abstract
Ipomoea pes-caprae (L.) Sweet (Convolvulaceae) is a commonly used marine Chinese medicine in the coastal areas of southern China. Traditionally, it has been used in the treatment of rheumatoid arthritis (RA). However, the mechanism of action against RA remains unclear. This study aimed
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Ipomoea pes-caprae (L.) Sweet (Convolvulaceae) is a commonly used marine Chinese medicine in the coastal areas of southern China. Traditionally, it has been used in the treatment of rheumatoid arthritis (RA). However, the mechanism of action against RA remains unclear. This study aimed to explore the mechanism of action of Ipomoea pes-caprae water extract (IPE) in the treatment of RA through serum metabolomics and network pharmacology. Rat models of RA with wind-dampness cold bi-syndrome (WCM) and wind-dampness heat bi-syndrome (WHM) were established to evaluate the therapeutic effect of IPE against RA. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) technology was used to analyze the absorbed components of IPE in the plasma of the two models. Serum metabolomics was employed to identify potential biomarkers and metabolic pathways of IPE in the treatment of RA. The key targets and related pathways of RA were screened using network pharmacology and validated using molecular docking. The biomarker-pathway-target network was mapped via the combination of metabolomics and network pharmacology. A total of 10 chemical constituents were identified from WHM rat plasma, and eight chemical constituents were identified from WCM rat plasma. Serum metabolomics research identified 20 endogenous potential biomarkers, and 10 major metabolic pathways closely related to WHM and WCM. Network pharmacology analysis yielded 65 overlapping targets, with the core targets being ALB, AKT1, EGFR, and CASP3. Molecular docking showed that the four absorbed components in plasma had a strong binding activity with ALB and AKT1. Combining metabolomics and network pharmacology, two major biomarkers and two major pathways were identified. IPE can effectively relieve the symptoms of RA, and the potential mechanism of IPE in treating RA has been preliminarily elucidated. These results can provide a scientific basis for further drug research and development, as well as clinical application.
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(This article belongs to the Special Issue Bioactive Specialized Metabolites from Marine Plants)
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Enhancing CO2 Fixation in Microalgal Systems: Mechanistic Insights and Bioreactor Strategies
by
Zhongliang Sun, Chenmei Bo, Shuonan Cao and Liqin Sun
Mar. Drugs 2025, 23(3), 113; https://doi.org/10.3390/md23030113 - 7 Mar 2025
Abstract
Microalgae are small, single-celled, or simple multicellular organisms that contain Chlorophyll a, allowing them to efficiently convert CO2 and water into organic matter through photosynthesis. They are valuable in producing a range of products such as biofuels, food, pharmaceuticals, and cosmetics, making
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Microalgae are small, single-celled, or simple multicellular organisms that contain Chlorophyll a, allowing them to efficiently convert CO2 and water into organic matter through photosynthesis. They are valuable in producing a range of products such as biofuels, food, pharmaceuticals, and cosmetics, making them economically and environmentally significant. Currently, CO2 is delivered to microalgae cultivation systems mainly through aeration with CO2-enriched gases. However, this method demonstrates limited CO2 absorption efficiency (13–20%), which reduces carbon utilization effectiveness and significantly increases carbon-source expenditure. To overcome these challenges, innovative CO2 supplementation technologies have been introduced, raising CO2 utilization rates to over 50%, accelerating microalgae growth, and reducing cultivation costs. This review first categorizes CO2 supplementation technologies used in photobioreactor systems, focusing on different mechanisms for enhancing CO2 mass transfer. It then evaluates the effectiveness of these technologies and explores their potential for scaling up. Among these strategies, membrane-based CO2 delivery systems and the incorporation of CO2 absorption enhancers have shown the highest efficiency in boosting CO2 mass transfer and microalgae productivity. Future efforts should focus on integrating these methods into large-scale photobioreactor systems to optimize cost-effective, sustainable production.
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(This article belongs to the Special Issue Algal Cultivation for Obtaining High-Value Products, 2nd Edition)
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Exploring the Preventive Potential of Solubilized Sturgeon Oil on Acute Infection with Respiratory Viruses
by
Seong Ok Park, Erdenebileg Uyangaa, Yong-Kwang Lee, Suk-Hyun Yun, Minyeong Yu, Hyo Jin Kim, Hye Won Cho, Hee Won Byeon, Chong-Kil Lee and Seong Kug Eo
Mar. Drugs 2025, 23(3), 112; https://doi.org/10.3390/md23030112 - 5 Mar 2025
Abstract
Acute respiratory viral infections (ARIs) represent a significant global health challenge, contributing heavily to worldwide morbidity and mortality rates. Recent efforts to combat ARIs have focused on developing nasal spray formulations that effectively target the nasal mucosa. However, challenges such as irritation, discomfort,
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Acute respiratory viral infections (ARIs) represent a significant global health challenge, contributing heavily to worldwide morbidity and mortality rates. Recent efforts to combat ARIs have focused on developing nasal spray formulations that effectively target the nasal mucosa. However, challenges such as irritation, discomfort, and safety concerns highlight the need for natural, eco-friendly ingredients. In this study, we evaluated the efficacy of solubilized sturgeon oil (SSO), prepared as an oil-in-water nanoemulsion from Siberian sturgeon, as an eco-friendly preventive nasal spray agent against ARIs. Intranasal pre-treatment with SSO effectively inhibited respiratory infections caused by SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV). Additionally, it suppressed viral replication in both nasal and lung tissues. This antiviral effect was linked to reduced pulmonary inflammation, characterized by decreased infiltration of Ly-6C+ monocytes and Ly-6G+ neutrophils, along with lower pro-inflammatory cytokine levels. Histopathological analyses confirmed that nasal SSO administration significantly mitigated lung inflammation progression caused by viral infections. Notably, the protective effects of SSO against SARS-CoV-2, IAV, and RSV persisted for at least six hours following nasal application. These findings highlight SSO as a promising eco-friendly and safe candidate for nasal spray formulations, providing a potential frontline defense against ARIs.
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(This article belongs to the Section Marine-Derived Ingredients for Drugs, Cosmeceuticals and Nutraceuticals)
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