Marine Drugs

13 pages, 30755 KB

Open AccessArticle

Isolation, Structural Elucidation, and Biological Evaluation of Pyrrole-Based Alkaloids from Sea Anemone-Associated Streptomyces sp. S1502

by Xin Zhang, Qihong Yang, Le Zhou, Yingying Chen, Jianhua Ju and Junying Ma

Mar. Drugs 2026, 24(1), 51; https://doi.org/10.3390/md24010051 - 21 Jan 2026

Abstract

Three new pyrrole alkaloids, streptopyrroles D–F (1–3), along with four known analogs (4–7) were isolated from Sea Anemone-Associated Streptomyces sp. S1502 via an OSMAC (One Strain Many Compounds)-based strategy. Their structures were elucidated through comprehensive [...] Read more.

Three new pyrrole alkaloids, streptopyrroles D–F (1–3), along with four known analogs (4–7) were isolated from Sea Anemone-Associated Streptomyces sp. S1502 via an OSMAC (One Strain Many Compounds)-based strategy. Their structures were elucidated through comprehensive spectroscopic analyses, including HRESIMS and 1D/2D NMR experiments (COSY, HSQC, and HMBC), and further confirmed by X-ray crystallography. Biological evaluation identified streptopyrrole (4) as an anti-MRSA (methicillin-resistant Staphylococcus aureus) agent, while 4 and 6 displayed broad-spectrum cytotoxicity and good selectivity against a panel of human cancer cell lines. Notably, 4 and 6 showed particularly potent activity against the lung cancer cell lines H1299, SW1573, and A549, with IC₅₀ values ranging from 5.43 to 16.24 μM. Further mechanistic investigation revealed that both compounds suppress the proliferation of lung cancer cells by inducing cell cycle arrest at the G0/G1 phase and impair metastatic potential by inhibiting migration and invasion. These findings not only expand the structural diversity of marine-derived pyrrole alkaloids but also reveal the anticancer mechanisms of 4 and 6, highlighting their promise as active candidates for further antitumor drug development, particularly in lung cancer. Full article

(This article belongs to the Section Marine Pharmacology)

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12 pages, 8765 KB

Open AccessFeature PaperArticle

Aptamer-Based Dual-Cascade Signal Amplification System Lights up G-Quadruplex Dimers for Ultrasensitive Detection of Domoic Acid

by Jiansen Li, Zhenfei Xu, Zexuan Zhang, Rui Liu, Yuping Zhu, Xiaoling Lu, Huiying Xu, Xiaoyu Liu, Zhe Ning, Xinyuan Wang, Haobing Yu and Bo Hu

Mar. Drugs 2026, 24(1), 50; https://doi.org/10.3390/md24010050 - 21 Jan 2026

Abstract

In recent years, harmful algal blooms have led to frequent occurrences of shellfish toxin contamination, posing a significant threat to the safety of aquatic products and public health. As a potent neurotoxin, domoic acid (DA) can accumulate in shellfish, highlighting the urgent need [...] Read more.

In recent years, harmful algal blooms have led to frequent occurrences of shellfish toxin contamination, posing a significant threat to the safety of aquatic products and public health. As a potent neurotoxin, domoic acid (DA) can accumulate in shellfish, highlighting the urgent need for rapid and highly sensitive detection methods. In this study, we developed a fluorescent aptasensor based on a dual-signal amplification system by combining G-quadruplex (G4) dimers with multi-walled carbon nanotubes (CNTs). The sensor is designed with a hairpin-structured aptamer as the recognition probe, where short multi-walled CNTs serve as both a fluorescence quencher and platform, and G4 dimers are incorporated into the sensing interface to enhance signal output. In the absence of the target, the hairpin-structured aptamer remains closed, keeping the fluorescence signal “off”. Upon binding to DA, the aptamer undergoes a specific conformational change that exposes the G4-dimer sequence. The exposed sequence then binds to thioflavin T (ThT), which in turn generates a greatly enhanced fluorescence signal, leading to a substantial fluorescence enhancement and completing the second stage of the cascade amplification. Under optimal conditions, the constructed sensor achieves rapid detection of DA within 5 min, with a low detection limit of 1.1 ng/mL. This work presents a valuable tool for the rapid and sensitive detection of DA in shellfish, with promising applications in marine environmental monitoring and food safety regulation. Full article

(This article belongs to the Special Issue Marine Biotoxins, 4th Edition)

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14 pages, 1008 KB

Open AccessArticle

Acute Intravenous Astaxanthin Administration Modulates Hyperexcitability in Rat Nociceptive Secondary Sensory Neurons Induced by Inflammation

by Risako Chida and Mamoru Takeda

Mar. Drugs 2026, 24(1), 49; https://doi.org/10.3390/md24010049 - 21 Jan 2026

Abstract

Previous in vivo studies have clearly demonstrated that the intravenous administration of the carotenoid astaxanthin (AST) suppresses the excitability of rat trigeminal spinal nucleus caudalis (SpVc) neurons. This action is hypothesized to be mediated through the inhibition of both voltage-gated Ca²⁺ (Cav) [...] Read more.

Previous in vivo studies have clearly demonstrated that the intravenous administration of the carotenoid astaxanthin (AST) suppresses the excitability of rat trigeminal spinal nucleus caudalis (SpVc) neurons. This action is hypothesized to be mediated through the inhibition of both voltage-gated Ca²⁺ (Cav) channels and excitatory glutamate receptor transmission. The objective of this study was to determine whether acute intravenous administration of AST alleviates the hyperexcitability of SpVc wide dynamic range (WDR) neurons in a rat model of inflammation. Neuronal responses to both nociceptive and non-nociceptive mechanical stimulation were evaluated using an in vivo electrophysiological model. One day following inflammation induced by Complete Freund’s Adjuvant (CFA), the mechanical escape threshold was significantly reduced compared to pre-injection baseline values. Subsequently, extracellular single-unit recordings were performed on SpVc WDR neurons in anesthetized, inflamed rats. The neuronal responses to both non-noxious and noxious orofacial mechanical stimuli were then analyzed. Acute intravenous administration of AST at 1 and 5 mM elicited a dose-dependent reduction in the mean firing frequency of SpVc WDR neurons in response to noxious mechanical stimuli. This inhibition peaked within 10 min and was fully reversed after approximately 25 min. Importantly, AST preferentially inhibited the discharge frequency of SpVc WDR neurons in response to noxious stimulation, exhibiting a significantly greater effect than on the response evoked by non-noxious stimulation (41.5 ± 3.0% vs. 20.7 ± 4.2%, p < 0.05). Collectively, these findings demonstrate that acute intravenous administration of AST effectively suppresses noxious synaptic transmission within the SpVc during inflammation. We propose that this suppressive effect is mediated by the inhibition of upregulated Cav channels and glutamate receptors. Consequently, AST is implicated as a promising therapeutic candidate for the management of trigeminal inflammatory pain, given its potential for a favorable safety profile compared to conventional treatments. Full article

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

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12 pages, 2466 KB

Open AccessArticle

Design and Synthesis of Marine Sarocladione Derivatives with Potential Anticancer Activity

by Xiao-Mei Liu, Wen-Xuan Li, Ling-Xiu Kong, Guan-Ying Han, Jinghan Gui and Xu-Wen Li

Mar. Drugs 2026, 24(1), 48; https://doi.org/10.3390/md24010048 - 20 Jan 2026

Abstract

The discovery of structurally novel anti-tumor agents remains a crucial objective in cancer drug research. In this study, we systematically explored the bioactivity potential of sarocladione (5), a structurally unique marine-derived 14-membered ring diketone steroid. Guided by a function-oriented strategy, seven [...] Read more.

The discovery of structurally novel anti-tumor agents remains a crucial objective in cancer drug research. In this study, we systematically explored the bioactivity potential of sarocladione (5), a structurally unique marine-derived 14-membered ring diketone steroid. Guided by a function-oriented strategy, seven new derivatives (6–13) were synthesized based on an efficient biomimetic synthesis of sarocladione. Evaluation of their antiproliferative activities against human cancer cell lines demonstrated that the intact macrocyclic scaffold is indispensable for activity. Extension of the conjugated π-system led to the identification of compound 8, which exhibited approximately four-fold enhanced potency against HCT116 cells (IC₅₀ = 1.86 µM) compared with the parent natural product. Stereochemical analysis further revealed the critical role of the (5R)-configuration at C-5. Phenotypic investigations indicated that compound 8 induces concentration-dependent G2/M phase cell cycle arrest, followed by apoptosis, suggesting a cell cycle-dependent antiproliferative effect. Overall, this study highlights sarocladione as a promising marine-derived scaffold for further antiproliferative optimization. Full article

(This article belongs to the Special Issue Synthesis, Optimization and Biological Activity of Marine Natural Product)

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15 pages, 3126 KB

Open AccessArticle

A Novel Bis-Spiroketal Scaffold and Other Secondary Metabolites from the Marine-Derived Fungus Talaromyces stipitatus HF05001: Structural Diversity and Bioactivities

by Longhe Yang, Yan Qiu, Ying Liu, Xiaoyu Wei, Xiwen He, Yiling Wang, Yajun Yan, Kaikai Bai, Zhaokai Wang and Jie Ren

Mar. Drugs 2026, 24(1), 47; https://doi.org/10.3390/md24010047 - 19 Jan 2026

Abstract

Marine-derived fungi have become a vital resource for the discovery of novel secondary metabolites with diverse structures and significant biological activities. This study focuses on a systematic chemical investigation of the sponge-associated fungus Talaromyces stipitatus HF05001, leading to the isolation and identification of [...] Read more.

Marine-derived fungi have become a vital resource for the discovery of novel secondary metabolites with diverse structures and significant biological activities. This study focuses on a systematic chemical investigation of the sponge-associated fungus Talaromyces stipitatus HF05001, leading to the isolation and identification of 20 compounds, including one new marine ketal natural product (Compound 17, Talarobispiral A). These compounds were structurally elucidated using comprehensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS. All isolates were screened for their anti-inflammatory and anti-adipogenic properties. Among them, compound 4 (Secalonic acid D, SAD), 7 (Sch 725680) and 16 (bacillisporins C) demonstrated significant anti-inflammatory potential by markedly suppressing nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Notably, compound 4 showed superior inhibitory effect, with an IC₅₀ value of 0.22 μM. Additionally, compound 4 exhibited the strongest dose-dependent inhibition of lipid droplet accumulation in 3T3-L1 preadipocytes. These findings highlight the dual therapeutic potential of metabolites from Talaromyces stipitatus, identifying promising lead compounds for the development of novel treatments for inflammatory and metabolic disorders. Full article

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

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17 pages, 2179 KB

Open AccessArticle

Truncated Equinine B Variants Reveal the Sequence Determinants of Antimicrobial Selectivity

by Mariele Staropoli, Theresa Schwaiger, Jasmina Tuzlak, Renata Biba, Lukas Petrowitsch, Johannes Fessler, Marin Roje, Matteo Cammarata, Nermina Malanović and Andreja Jakas

Mar. Drugs 2026, 24(1), 46; https://doi.org/10.3390/md24010046 - 17 Jan 2026

Abstract

Equinin B (GQCQRKCLGHCSKKCPKHPQCRKRCIRRCFGYCL), a marine peptide from Actinia equina exhibits antibacterial activity against both Gram-positive and Gram-negative bacteria. To identify a smaller active region and explore tunable properties, three peptide fragments were synthesized: GQCQRKCLGHCS (EB1), KKCPKHPQCRK (EB2), and RCIRRCFGYCL [...] Read more.

Equinin B (GQCQRKCLGHCSKKCPKHPQCRKRCIRRCFGYCL), a marine peptide from Actinia equina exhibits antibacterial activity against both Gram-positive and Gram-negative bacteria. To identify a smaller active region and explore tunable properties, three peptide fragments were synthesized: GQCQRKCLGHCS (EB1), KKCPKHPQCRK (EB2), and RCIRRCFGYCL (EB3), yielding peptides with key AMP-like properties, including the most positively charged and most hydrophobic regions. Only the 11-residue C-terminal fragment showed selective activity against Gram-positive bacteria, including Staphylococcus epidermidis, Bacillus subtilis, and Enterococcus hirae, while remaining inactive against Escherichia coli. Peptide modifications, achieved by replacing cysteine residues with arginine, generally did not enhance activity, but in the C-terminal fragment EB3 they reduced hemolytic activity and increased bacterial specificity. Membrane depolarization assays confirmed that the unmodified fragment EB3 strongly disrupts bacterial membranes, whereas the modified variant showed minimal depolarization, highlighting its markedly reduced membrane-disruptive potential. In silico modelling revealed that the EB3 can adopt multiple membrane-disruption modes, from transient shallow pores to carpet-like mechanisms, while the cysteine-to-arginine variant interacts mainly via partial insertion anchored by arginine residues. Phenylalanine appears to interact with the membrane, and reducing hydrophobicity by its removal abolished antibacterial activity. These findings highlight the 11-residue C-terminal fragment as a tunable, membrane-targeting motif with mechanistic novelty, offering a blueprint for developing safer, selective antimicrobial peptides with reduced cytotoxicity. Full article

(This article belongs to the Section Marine Pharmacology)

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24 pages, 5640 KB

Open AccessArticle

Recombinant Expression and Antimicrobial Mechanism of Cysteine-Rich Antimicrobial Peptides from Tigriopus japonicus Genome

by Dan Pu, Hongwei Tao, Jingwei Pang, Huishao Shi, Junjian Wang and Wei Zhang

Mar. Drugs 2026, 24(1), 45; https://doi.org/10.3390/md24010045 - 16 Jan 2026

Abstract

The misuse of antibacterial agents has contributed to the growing prevalence of antibiotic resistance, highlighting an urgent need to explore alternative anti-infection therapeutic strategies. Antimicrobial peptides (AMPs) are naturally occurring molecules. They exhibit broad-spectrum antimicrobial activity and represent promising candidates for the development [...] Read more.

The misuse of antibacterial agents has contributed to the growing prevalence of antibiotic resistance, highlighting an urgent need to explore alternative anti-infection therapeutic strategies. Antimicrobial peptides (AMPs) are naturally occurring molecules. They exhibit broad-spectrum antimicrobial activity and represent promising candidates for the development of novel therapeutics. A cysteine-rich antimicrobial peptide was identified and characterized from the genome of Tigriopus japonicus and designated “TjRcys1”. The precursor form of TjRcys1 comprises 96 amino acids. Structural analyses of TjRcys1 revealed random coils, two α-helices, and two β-strands. Recombinant TjRcys1 had inhibitory effects upon Staphylococcus aureus and Bacillus sp. T2, with a minimum inhibitory concentration of 64 μM for both. TjRcys1 did not show complete inhibition against Vibrio alginolyticus, Klebsiella pneumoniae, or Aeromonas hydrophila at 64 μM, but it did slow their growth rate. TjRcys1 could disrupt the permeability of the cell membrane of S. aureus. Transcriptomic analyses indicated that TjRcys1 could interfere with the ribosome biosynthesis and nucleotide metabolism of K. pneumoniae. Our results provide a valuable reference for the development of new AMPs and optimization of their design. Full article

(This article belongs to the Special Issue Marine Antimicrobial Peptides and Antibiotic Resistance: From Oceanic Defense Systems to Translational Applications)

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39 pages, 2612 KB

Open AccessReview

Marine Bacteria as a Source of Antibiotics Against Staphylococcus aureus: Natural Compounds, Mechanisms of Action, and Discovery Strategies

by Céphas Xuma, Alexandre Bourles, Julien Colot, Linda Guentas and Mariko Matsui

Mar. Drugs 2026, 24(1), 44; https://doi.org/10.3390/md24010044 - 15 Jan 2026

Abstract

Staphylococcus aureus is a major opportunistic pathogen responsible for a wide spectrum of human infections, including severe and difficult-to-treat cases. The emergence of multidrug-resistant strains limits the efficacy of conventional antibiotic therapies and poses a significant global public health challenge. In this context, [...] Read more.

Staphylococcus aureus is a major opportunistic pathogen responsible for a wide spectrum of human infections, including severe and difficult-to-treat cases. The emergence of multidrug-resistant strains limits the efficacy of conventional antibiotic therapies and poses a significant global public health challenge. In this context, the search for novel antibiotics has intensified, with increasing interest in marine resources, an ecosystem still largely underexplored. Marine bacteria produce a vast array of secondary metabolites with unique structures and potentially novel modes of antibacterial action. Several compounds isolated from marine bacterial strains have demonstrated promising activity against multidrug-resistant S. aureus, including antivirulence effects such as biofilm formation and Quorum-Sensing inhibition. This review explores the potential of marine bacteria as a source of new antibiotics against S. aureus, discusses both classical and advanced strategies for the discovery of bioactive molecules, and highlights the scientific and technological challenges involved in translating these findings into clinical applications. Full article

(This article belongs to the Section Marine Pharmacology)

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18 pages, 2594 KB

Open AccessArticle

Hippocampal Metabolomics Reveal the Mechanism of α-Conotoxin [S9K]TxID Attenuating Nicotine Addiction

by Meiting Wang, Weifeng Xu, Huanbai Wang, Cheng Cui, Rongyan He, Xiaodan Li, Jinpeng Yu, J. Michael McIntosh, Dongting Zhangsun and Sulan Luo

Mar. Drugs 2026, 24(1), 43; https://doi.org/10.3390/md24010043 - 15 Jan 2026

Abstract

Nicotine is the main substance responsible for the development of tobacco addiction. The α3β4 nicotinic acetylcholine receptors (nAChRs) are a potential key target for mitigating nicotine reward. Preliminary studies in our laboratory suggest that α-conotoxin [S9K]TxID serves as a selective and potent antagonist [...] Read more.

Nicotine is the main substance responsible for the development of tobacco addiction. The α3β4 nicotinic acetylcholine receptors (nAChRs) are a potential key target for mitigating nicotine reward. Preliminary studies in our laboratory suggest that α-conotoxin [S9K]TxID serves as a selective and potent antagonist targeting α3β4 nAChRs, which may be beneficial in addressing nicotine addiction. However, the mechanisms of [S9K]TxID treatment in nicotine addiction are still to be determined. This study aimed to identify the differential metabolic profiles of [S9K]TxID treatment in nicotine addiction using an untargeted metabolomic profiling method. As demonstrated by behavioral experiments, [S9K]TxID effectively attenuated nicotine-induced conditioned place preference (CPP) expression without exerting inhibitory effects on the central nervous system (CNS). The results of untargeted metabolomics revealed that eight metabolites were significantly altered after [S9K]TxID treatment, particularly phenylalanine. [S9K]TxID also attenuated nicotine-induced metabolic disorders by regulating phenylalanine, tyrosine and tryptophan biosynthesis. In conclusion, our findings suggest that [S9K]TxID could be a potential therapeutic compound for nicotine addiction. Full article

(This article belongs to the Section Marine Toxins)

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16 pages, 4420 KB

Open AccessArticle

Fucoidan Extracted from Fucus vesiculosus Ameliorates Colitis-Associated Neuroinflammation and Anxiety-like Behavior in Adult C57BL/6 Mice

by Xiaoyu Song, Na Li, Xiujie Li, Bo Yuan, Xuan Zhang, Sheng Li, Xiaojing Yang, Bing Qi, Shixuan Yin, Chunxue Li, Yangting Huang, Ben Zhang, Yanjie Guo, Jie Zhao and Xuefei Wu

Mar. Drugs 2026, 24(1), 42; https://doi.org/10.3390/md24010042 - 14 Jan 2026

Abstract

Fucoidan, a complex sulfated polysaccharide derived from marine brown seaweeds, exhibits broad biological activities, including anticoagulant, antitumor, antiviral, anti-inflammatory and lipid-lowering effects. Fucoidan confers neuroprotection in animal models of a broad spectrum of brain disorders such as Parkinson’s disease (PD) and depression. However, [...] Read more.

Fucoidan, a complex sulfated polysaccharide derived from marine brown seaweeds, exhibits broad biological activities, including anticoagulant, antitumor, antiviral, anti-inflammatory and lipid-lowering effects. Fucoidan confers neuroprotection in animal models of a broad spectrum of brain disorders such as Parkinson’s disease (PD) and depression. However, the effect of fucoidan on gut-derived neuroinflammation and associated behavioral changes has been scarcely investigated. In comparison to fucoidan from other brown seaweeds, that from Fucus vesiculosus exhibited a better neuroprotective effect in vivo and more potent radical scavenging activity in vitro. Fucoidan from Laminaria japonica ameliorates behavioral disorders related to acute ulcerative colitis (UC) in aged mice. It is of interest to assess the effects of fucoidan administration on intestinal and brain inflammation in the acute colitis mouse model. Fucoidan treatment ameliorated DSS-induced intestinal pathology, reduced the inflammatory mediator expression in the gut and brain, and activated intestinal macrophages and cortical microglia in the UC mice. It also protected the intestinal mucosal barrier and blood–brain barrier as well as prevented neuronal damage, while alleviating anxiety-like behavior in UC mice. These results suggest fucoidan supplementation may help prevent brain disorders, such as depression and PD, potentially involving gut–brain axis-related mechanisms, as fucoidan suppresses gut-derived neuroinflammation. Full article

(This article belongs to the Special Issue Advances in Research on Fucoidan: Potential as Drug and Functional Food)

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27 pages, 3030 KB

Open AccessArticle

Structural Characterization and Anti-Inflammatory Properties of an Alginate Extracted from the Brown Seaweed Ericaria amentacea

by Maha Moussa, Serena Mirata, Lisa Moni, Valentina Asnaghi, Marina Alloisio, Simone Pettineo, Maila Castellano, Silvia Vicini, Mariachiara Chiantore and Sonia Scarfì

Mar. Drugs 2026, 24(1), 41; https://doi.org/10.3390/md24010041 - 13 Jan 2026

Abstract

Brown algae of the Cystoseira genus are recognized as valuable sources of bioactive compounds, including polysaccharides. Within the framework of current restoration efforts regarding damaged Ericaria amentacea populations in the Mediterranean Sea, the valorization of apices derived from ex situ cultivation waste represents [...] Read more.

Brown algae of the Cystoseira genus are recognized as valuable sources of bioactive compounds, including polysaccharides. Within the framework of current restoration efforts regarding damaged Ericaria amentacea populations in the Mediterranean Sea, the valorization of apices derived from ex situ cultivation waste represents a sustainable opportunity for industrial and biomedical applications. In this study, sodium alginate (SA) was extracted from E. amentacea apex by-products using a hydrothermal–alkaline method and subsequently chemically characterized. FTIR analysis showed O-H, C-H, and COO- stretching compatible with commercial alginates, while 1H-NMR spectroscopy indicated high β-D-mannuronic acid content, with an M/G ratio of 2.33. The extracted SA displayed a molecular weight of 1 × 10⁴ g/mol and a polydispersity index of 3.5. The bioactive properties of the SA extract were investigated in chemico and in vitro. SA exhibited remarkable antioxidant activity, showing significant DPPH and nitric oxide-radical-scavenging capacity. Furthermore, SA demonstrated a strong anti-inflammatory effect in LPS-stimulated macrophages through modulation of several inflammatory mediators (i.e., IL-6, IL-8/CXCL5, MCP-1, and TNF-α). In particular, SA promoted a striking iNOS gene expression inhibition, which, paired with its direct NO-scavenging ability, paves the way for future pharmacological use of E. amentacea derivatives, particularly if sustainably obtained from restoration activity waste. Full article

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

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28 pages, 2998 KB

Open AccessArticle

Transcriptomic Insights into Metabolic Reprogramming and Exopolysaccharide Synthesis in Porphyridium purpureum Under Gradual Nitrogen Deprivation

by Maurean Guerreiro, Coline Emmanuel, Céline Dupuits, Christine Gardarin, Said Mouzeyar, João Varela, Jane Roche and Céline Laroche

Mar. Drugs 2026, 24(1), 40; https://doi.org/10.3390/md24010040 - 13 Jan 2026

Abstract

Porphyridium species are known red microalgae for producing valuable bioactive compounds such as sulfated exopolysaccharides (EPS) with diverse industrial biomedical applications due to their functional and rheological properties. Recent studies have investigated how abiotic stresses, particularly nitrogen deprivation, affect Porphyridium’s metabolic regulation [...] Read more.

Porphyridium species are known red microalgae for producing valuable bioactive compounds such as sulfated exopolysaccharides (EPS) with diverse industrial biomedical applications due to their functional and rheological properties. Recent studies have investigated how abiotic stresses, particularly nitrogen deprivation, affect Porphyridium’s metabolic regulation and EPS production through transcriptomic analysis. Still, the mechanisms governing EPS biosynthesis and the involvement of carbohydrate-activated enzymes (CAZymes) remain poorly understood. This study investigated the progressive effects of nitrate consumption on the unicellular red alga, P. purpureum, by integrating physiological, biochemical, and transcriptomic analyses through RNA-Seq, further validated by RT-qPCR. P. purpureum displayed a gradual, phase-dependent metabolic response to progressive nitrogen stress. EPS release coincided with the decline in nitrate uptake, linking nitrogen availability to carbon redirection towards polysaccharide secretion. Transcriptomic data revealed global metabolic downregulation with targeted upregulation of stress-responsive, carbohydrate catabolic, and nucleotide–sugar synthesis pathways, including the upregulation of CAZyme families GT4, GT8, and GT77. Our results give insights into the coordinated nitrogen and carbon metabolic regulation underlying polysaccharide biosynthesis, while opening future perspectives on enzyme compartmentalization and regulatory flux distribution under nitrogen stress in P. purpureum. Full article

(This article belongs to the Special Issue Polysaccharides from Marine Environment)

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20 pages, 3202 KB

Open AccessArticle

Discovery of a Marine Beauveria bassiana Polysaccharide with Antiviral Activity Against Tobacco Mosaic Virus

by Xu Qiu, Lihang Jiao, Jingjing Xue, Guangxin Xu and Xixiang Tang

Mar. Drugs 2026, 24(1), 39; https://doi.org/10.3390/md24010039 - 13 Jan 2026

Abstract

Tobacco mosaic virus (TMV) threatens crop yield and quality, while chemical antivirals offer limited efficacy and potential environmental hazards. Marine fungal polysaccharides are promising eco-friendly alternatives due to their biocompatibility and biodegradability. Here, extracellular polysaccharides (EPSs) from the deep-sea fungus Beauveria bassiana T2-2 [...] Read more.

Tobacco mosaic virus (TMV) threatens crop yield and quality, while chemical antivirals offer limited efficacy and potential environmental hazards. Marine fungal polysaccharides are promising eco-friendly alternatives due to their biocompatibility and biodegradability. Here, extracellular polysaccharides (EPSs) from the deep-sea fungus Beauveria bassiana T2-2 was isolated, characterized, and produced under optimized conditions (28 °C, 200 rpm, 9 days, pH 8, inoculum 4%) using an L9 (3⁴) orthogonal medium, yielding 3.42 g/L, which is a 48% increase over unoptimized culture. EPSs were glucose-rich, with a molecular weight of 3.56 × 10⁴ Da, containing 90.05% total sugar, 0.28% protein, 1.15% uronic acid, and 1.18% sulfate. In a Nicotiana benthamiana–TMV model, EPSs alleviated viral symptoms, maintained chlorophyll content, enhanced antioxidant enzymes (SOD, POD, CAT), reduced malondialdehyde, and upregulated defense genes in SA, ET, ROS, and phenylpropanoid pathways. EPSs, alone or combined with Ribavirin, activated multi-pathway antiviral immunity, highlighting its potential as a sustainable plant-protective agent. Full article

(This article belongs to the Special Issue Polysaccharides from Marine Environment)

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16 pages, 2301 KB

Open AccessArticle

Anti-Neuroinflammatory Effects of a Representative Low-Molecular-Weight Component Isolated from Codium fragile Through Inhibition of the NF-κB Pathway in Microglia and Macrophage Cells

by Gyoyoung Lee, Yezhi Jin, Seul Ah Lee, Sook-Young Lee, Hwan Lee, Zisheng Nan, Chi-Su Yoon and Dong-Sung Lee

Mar. Drugs 2026, 24(1), 38; https://doi.org/10.3390/md24010038 - 13 Jan 2026

Abstract

The worldwide incidence of neurodegenerative diseases (ND), such as dementia, has increased, and neuroinflammation is considered a crucial factor in the development of ND. Codium fragile is considered ocean waste in many countries; however, some countries, including Korea, consume it as a food [...] Read more.

The worldwide incidence of neurodegenerative diseases (ND), such as dementia, has increased, and neuroinflammation is considered a crucial factor in the development of ND. Codium fragile is considered ocean waste in many countries; however, some countries, including Korea, consume it as a food resource. In this study, a major low-molecular-weight component and chemical marker, uracil, was isolated from the aqueous extracts of C. fragile (AECF); additionally, its content was measured through HPLC quantitative analysis. AECF and uracil were examined for their anti-inflammatory activities against lipopolysaccharide (LPS)-stimulated BV2 microglia and RAW264.7 macrophage cell lines under inflammation conditions. The results showed that AECF and uracil inhibited the production of pro-inflammatory cytokines by suppressing the NF-κB pathway. Full article

(This article belongs to the Special Issue Research on Marine Compounds and Inflammation)

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16 pages, 2407 KB

Open AccessArticle

Discovery of RUVBL1 as a Target of the Marine Alkaloid Caulerpin via MS-Based Functional Proteomics

by Alessandra Capuano, Gilda D’Urso, Lucia Capasso, Emilio Brancaccio, Erica Gazzillo, Marianna Carbone, Ernesto Mollo, Gianluigi Lauro, Maria Giovanna Chini, Giuseppe Bifulco, Angela Nebbioso and Agostino Casapullo

Mar. Drugs 2026, 24(1), 37; https://doi.org/10.3390/md24010037 - 10 Jan 2026

Abstract

Marine flora is a significant source of bioactive metabolites. These compounds have been demonstrated to have outstanding bioactivity and biocompatibility, enabling their use in various therapeutic applications. Therefore, examining the biological potential of marine natural compounds remains important, with particular emphasis on their [...] Read more.

Marine flora is a significant source of bioactive metabolites. These compounds have been demonstrated to have outstanding bioactivity and biocompatibility, enabling their use in various therapeutic applications. Therefore, examining the biological potential of marine natural compounds remains important, with particular emphasis on their interaction profiles to identify the macromolecular partners they can modulate. This study focused on the interactome profiling of the marine alkaloid caulerpin (CAU), isolated from the alga Caulerpa cylindracea. Along with the discovery of its antitumor properties, this metabolite has garnered attention for its potential therapeutic applications, including modulation of MAO-B and PPARs involved in inflammatory responses, as well as the discovery of its antitumor properties. Two complementary MS-based proteomic approaches were used to identify CAU target proteins in cancer cells: DARTS, which enabled proteome-wide screening to identify proteins interacting with the compound, and t-LIP-MRM-MS, which pinpointed the target protein regions involved in ligand binding. RUVB-like 1 (RUVBL1), a protein that regulates the essential mechanism of carcinogenesis, including chromatin remodeling, DNA repair, and transcriptional control, was discovered as an intriguing CAU target. These results were corroborated via in silico and biological investigations that elucidated CAU role in the regulation of RUVBL1 activity, highlighting its promising therapeutic relevance. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 5th Edition)

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16 pages, 1035 KB

Open AccessArticle

Proteomic and Functional Characterization of Antimicrobial Peptides Derived from Fisheries Bycatch via Enzymatic Hydrolysis

by Vicky Balesteros S. Blumen Galendi, Guilherme Rabelo Coelho, Letícia Murback, Wagner C. Valenti, Tavani Rocha Camargo, Marcia Regina Franzolin, Daniel Carvalho Pimenta and Rui Seabra Ferreira, Jr.

Mar. Drugs 2026, 24(1), 36; https://doi.org/10.3390/md24010036 - 10 Jan 2026

Abstract

Fisheries bycatch, while representing a major ecological concern due to the incidental capture of non-target species, also constitutes an underexplored source of marine biomass with biotechnological potential. This study aimed to generate and characterize bioactive peptides from the muscle tissue of three common [...] Read more.

Fisheries bycatch, while representing a major ecological concern due to the incidental capture of non-target species, also constitutes an underexplored source of marine biomass with biotechnological potential. This study aimed to generate and characterize bioactive peptides from the muscle tissue of three common bycatch species from the Brazilian coast: Paralonchurus brasiliensis, Micropogonias furnieri, and Hepatus pudibundus. Muscle homogenates were hydrolyzed using either Alcalase or Protamex to produce peptide-rich hydrolysates, which were analyzed through SDS-PAGE, HPLC-UV, MALDI-TOF, and LC-MS/MS. De novo sequencing and bioinformatic analyses predicted bioactivities that were subsequently validated by in vitro assays. The results demonstrated that enzyme selection strongly influenced both peptide profiles and bioactivity. The Protamex hydrolysate of P. brasiliensis (PBP) exhibited potent antifungal activity, inhibiting Candida albicans growth by 81%, whereas the Alcalase hydrolysate (PBA) showed moderate inhibition of Staphylococcus aureus (29%). No significant effect was observed against Escherichia coli. Overall, this study highlights a sustainable strategy for the valorization of fisheries bycatch through the production of bioactive marine peptides and identifies P. brasiliensis hydrolyzed with Protamex as a promising source of anti-Candida peptides for pharmaceutical and nutraceutical applications. Full article

(This article belongs to the Special Issue Marine Antimicrobial Peptides and Antibiotic Resistance: From Oceanic Defense Systems to Translational Applications)

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22 pages, 5055 KB

Open AccessArticle

Structural and Mechanistic Insights into Dual Cholinesterase Inhibition by Marine Phytohormones

by Kumju Youn, Legie Mae Soriano and Mira Jun

Mar. Drugs 2026, 24(1), 35; https://doi.org/10.3390/md24010035 - 9 Jan 2026

Abstract

Cholinergic dysfunction is a hallmark of Alzheimer’s disease (AD), driven by elevated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity that depletes acetylcholine and contributes to amyloid pathology. Current AD treatments face major challenges, including poor brain penetration, short effect duration and safety concerns, highlighting [...] Read more.

Cholinergic dysfunction is a hallmark of Alzheimer’s disease (AD), driven by elevated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity that depletes acetylcholine and contributes to amyloid pathology. Current AD treatments face major challenges, including poor brain penetration, short effect duration and safety concerns, highlighting the need for compounds suitable for preventive or earlier-stage intervention. This study investigated marine phytohormones as modulators of cholinergic imbalance, using an integrative strategy encompassing enzymatic assays, QSAR and DFT calculations, molecular docking, molecular dynamics (MD) simulations, and ADMET profiling. Among them, isopentenyl adenine (IPA) and abscisic acid (ABA) showed inhibitory activity against cholinesterases. IPA inhibited both AChE and BChE through distinct mechanisms with noncompetitive inhibition of AChE and competitive inhibition of BChE, while ABA showed selective noncompetitive inhibition of AChE. DFT-based analysis revealed distinct electronic properties supporting differential reactivity. Moreover, IPA interacted with both catalytic and peripheral residues in AChE, and aligned with BChE’s active site, while ABA was bound more peripherally. MD simulations confirmed complex-specific conformational stability based on RMSD, RMSF, Rg, and hydrogen bonding analysis. Both compounds showed low off-target potential against serine proteases and favorable predicted ADMET profiles. These results support the potential of marine phytohormones as preventive modulators of cholinergic dysfunction in AD. Full article

(This article belongs to the Special Issue Marine Natural Products as Enzyme Inhibitors)

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12 pages, 1903 KB

Open AccessArticle

Chemical Investigation of the Global Regulator veA-Overexpressed Mutant of an Arctic Strain Aspergillus sydowii MNP-2

by Qing Gong, Wei Wang, Yujie Zhao, Xiaoying Wang, Xuelian Bai and Huawei Zhang

Mar. Drugs 2026, 24(1), 34; https://doi.org/10.3390/md24010034 - 9 Jan 2026

Abstract

A growing body of evidence indicates that artificial manipulation of transcriptional regulation is a powerful approach to activate cryptic biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) in fungi. In this study, one mutant strain MNP-2-OE::veA was constructed by overexpressing the global [...] Read more.

A growing body of evidence indicates that artificial manipulation of transcriptional regulation is a powerful approach to activate cryptic biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) in fungi. In this study, one mutant strain MNP-2-OE::veA was constructed by overexpressing the global transcription regulator veA in an Arctic-derived strain Aspergillus sydowii MNP-2. Chemical investigation of the mutant OE::veA resulted in the isolation of one novel polyhydroxy anthraquinone (1) together with nine known metabolites (2–10), which were unambiguously characterized by various spectroscopic methods including 1D and 2D NMR and HR-ESI-MS as well as via comparison with literature data. Biosynthetically, compounds 1 and 10 as new arising chemicals were, respectively, formed by type II polyketide synthase (T2PK) and non-ribosomal peptide synthetase (NRPS), which were silent in the wild-type (WT) strain MNP-2. A bioassay showed that only compound 3 had weak inhibitory effect on human pathogen Candida albicans, with a MIC value of 64 ug/mL, and 4 displayed in vitro weak cytotoxic activity against HCT116 cells (IC₅₀ = 44.47 μM). These results indicate that overexpression of veA effectively awakened the cryptic BGCs in fungal strains and enhanced their structural diversity in natural products. Full article

(This article belongs to the Special Issue Structural Diversity in Marine Natural Products)

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12 pages, 2310 KB

Open AccessArticle

Isolation of Phycobiliproteins from Thermosynechococcus PCC 6715 by Foam Fractionation in Batch and Continuous Modes

by Anna Antecka, Rafał Szeląg and Stanisław Ledakowicz

Mar. Drugs 2026, 24(1), 33; https://doi.org/10.3390/md24010033 - 9 Jan 2026

Abstract

Phycobiliproteins are recognized as potential bioactive compounds and described as highly valued natural products for industrial and biotechnological applications. Moreover, they have been observed to possess antioxidant, anticancer/antineoplastic, and anti-inflammatory activities. Therefore, the search for new methods of their extraction and isolation is [...] Read more.

Phycobiliproteins are recognized as potential bioactive compounds and described as highly valued natural products for industrial and biotechnological applications. Moreover, they have been observed to possess antioxidant, anticancer/antineoplastic, and anti-inflammatory activities. Therefore, the search for new methods of their extraction and isolation is still ongoing. Foam fractionation, a bubble separation technique that allows amphiphilic molecules to be separated from their aqueous solutions, is a promising but understudied method. The process may be carried out both under mild conditions that are suitable for proteins and also for diluted solutions. This paper presents the results of applying the foam fractionation process to concentrate and separate phycobiliproteins. Allo- and C-phycocyanin from a thermophilic Synechococcus PCC 6715 strain were used in extract form after biomass cultivation and disintegration. Two ways of running the process were investigated: batch mode and continuous mode, the latter of which has not been reported in the literature previously. The results indicate that the method can be applied on a larger scale, as the outcomes of the continuous mode processes were comparable to those of the batch mode. Moreover, the results indicate that the process provides, to a certain extent, the opportunity of separating phycobiliproteins from each other. Full article

(This article belongs to the Special Issue New Methods in Extraction and Isolation of Marine Natural Products)

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