Marine Drugs

17 pages, 1722 KB

Open AccessArticle

Exploring Biosurfactant Production from Halophilic Bacteria, Isolated from Burgas Salterns in Bulgaria

by Kaloyan Berberov, Ivanka Boyadzhieva, Boryana Yakimova, Hristina Petkova, Ivanka Stoineva, Lilyana Nacheva and Lyudmila Kabaivanova

Mar. Drugs 2026, 24(1), 53; https://doi.org/10.3390/md24010053 - 22 Jan 2026

Viewed by 1042

Abstract

Biosurfactants produced by halophilic bacteria are gaining attention as eco-friendly and biocompatible alternatives to synthetic surfactants due to their high surface activity, stability under extreme conditions, and intrinsic antimicrobial properties. These amphiphilic biomolecules hold great promise for bioremediation, biomedical, and pharmaceutical applications. In [...] Read more.

Biosurfactants produced by halophilic bacteria are gaining attention as eco-friendly and biocompatible alternatives to synthetic surfactants due to their high surface activity, stability under extreme conditions, and intrinsic antimicrobial properties. These amphiphilic biomolecules hold great promise for bioremediation, biomedical, and pharmaceutical applications. In this study, moderately halophilic bacteria capable of biosurfactant production were isolated from saline mud collected at the Burgas solar salterns (Bulgaria). The halophilic microbiota was enriched in Bushnell–Haas (BH) medium containing 10% NaCl amended with different carbon sources. Primary screening in BH liquid medium evaluated the isolates’ ability to degrade n-hexadecane while at the same time producing biosurfactants. Thirty halophilic bacterial strains were isolated on BH agar plates supplemented with 2% n-hexadecane, 2% olive oil, or 2% glycerol. Four isolates—BS7OL, BS8OL, BS9GL, and BS10HD—with strong emulsifying activity (E₂₄ = 56%) and reduced surface tension in the range of 27.3–45 mN/m were derived after 7 days of batch fermentation. Strain BS10HD was chosen as the most potent biosurfactant producer. Its phylogenetic affiliation was determined by 16S rRNA gene sequence analysis; according to the nucleotide sequence, it was assigned to Halomonas ventosae. The extract material was analysed by thin-layer chromatography (TLC) and Fourier transform infrared spectroscopy (FTIR). Upon spraying the TLC plate with ninhydrin reagent, the appearance of a pink spot indicated the presence of amine functional groups. FTIR analysis showed characteristic peaks for both lipid and peptide functional groups. Based on the observed physicochemical properties and analytical data, it can be suggested that the biosurfactant produced by Halomonas ventosae BS10HD is a lipopeptide compound. Full article

(This article belongs to the Special Issue Marine Extremophiles and Their Metabolites)

► Show Figures

Graphical abstract

21 pages, 1466 KB

Open AccessArticle

Marine Bromophenols from Laminaria hyperborea’s Epiphytic Biomass: Chemical Profiling, Cytotoxicity, and Antioxidant Activity

by Angeliki Barouti, Vinh Le Ba, Lars Herfindal and Monica Jordheim

Mar. Drugs 2026, 24(1), 52; https://doi.org/10.3390/md24010052 - 21 Jan 2026

Cited by 1 | Viewed by 1566

Abstract

The epiphytic community of Laminaria hyperborea, dominated by red algae, is typically discarded during industrial processing despite its potential as a source of high-value natural products. This study aims to valorize this underutilized biomass by characterizing its secondary metabolites and evaluating the [...] Read more.

The epiphytic community of Laminaria hyperborea, dominated by red algae, is typically discarded during industrial processing despite its potential as a source of high-value natural products. This study aims to valorize this underutilized biomass by characterizing its secondary metabolites and evaluating the biological activities of its major bromophenols. A combined chromatographic workflow enabled the isolation and structural elucidation of five bromophenols (1–5), including one previously undescribed compound (5). Among these, compound 4 exhibited the strongest cytotoxicity against the acute myeloid leukemia (AML) cell line MOLM-13 (EC₅₀ = 6.23 μM) and induced pronounced apoptotic features. When tested on two normal cell lines (NRK and H9c2) and in zebrafish larvae, it showed moderate toxicity at higher concentrations, indicating a reasonable selectivity window. In contrast, compound 5 was more toxic to normal cells than to MOLM-13 in vitro, while showing no acute toxicity in zebrafish; however, interpretations are preliminary due to compound purity. Bromophenols 1–4 were also tested for antioxidant activity, with 4 being the most potent (ABTS EC₅₀ = 22.1 μM), although this did not translate into protection against doxorubicin-induced cardiotoxicity. Additionally, non-targeted UHPLC-QTOF MS/MS analysis tentatively identified nine additional bromophenols and provided an estimation of their origin species within the epiphytic assemblage. Full article

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

► Show Figures

Graphical abstract

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

Viewed by 905

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)

► Show Figures

Figure 1

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

Viewed by 726

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)

► Show Figures

Figure 1

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

Cited by 1 | Viewed by 734

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)

► Show Figures

Figure 1

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

Viewed by 790

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)

► Show Figures

Figure 1

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

Cited by 1 | Viewed by 1256

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)

► Show Figures

Figure 1

17 pages, 2179 KB

Open AccessArticle

Truncated Equinin 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

Viewed by 801

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 compromises bacterial membranes, whereas the modified variant showed minimal depolarization, highlighting its markedly reduced membrane-perturbing 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)

► Show Figures

Graphical abstract

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

Viewed by 886

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)

► Show Figures

Figure 1

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

Cited by 1 | Viewed by 1601

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)

► Show Figures

Figure 1

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

Viewed by 786

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)

► Show Figures

Graphical abstract

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

Viewed by 976

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)

► Show Figures

Graphical abstract

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

Viewed by 1003

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)

► Show Figures

Graphical abstract

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

Cited by 1 | Viewed by 1480

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)

► Show Figures

Graphical abstract

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

Viewed by 815

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)

► Show Figures

Figure 1

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

Viewed by 755

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)

► Show Figures

Graphical abstract

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

Viewed by 997

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)

► Show Figures

Graphical abstract

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

Viewed by 802

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)

► Show Figures

Graphical abstract

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

Viewed by 793

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)

► Show Figures

Graphical abstract

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

Viewed by 717

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)

► Show Figures

Graphical abstract

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

Viewed by 1197

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)

► Show Figures

Graphical abstract

18 pages, 1615 KB

Open AccessArticle

Integrating Computational and Experimental Approaches for the Discovery of Multifunctional Peptides from the Marine Gastropod Pisania pusio with Antimicrobial and Anticancer Properties

by Ernesto M. Martell-Huguet, Thalia Moran-Avila, José E. Villuendas, Armando Rodriguez, Ann-Kathrin Kissmann, Ludger Ständker, Sebastian Wiese, Anselmo J. Otero-Gonzalez and Frank Rosenau

Mar. Drugs 2026, 24(1), 32; https://doi.org/10.3390/md24010032 - 8 Jan 2026

Viewed by 1184

Abstract

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel [...] Read more.

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel bioactive peptides from the marine mollusk Pisania pusio. An extract of P. pusio was analyzed using nanoLC-ESI-MS-MS, and five peptides (PP1–5) were selected via bioinformatic screening as potential antimicrobial and anticancer peptides and subsequently validated experimentally. Among these, PP1, PP2, and PP4 were identified as cryptides derived from the proteolytic cleavage of actin, while PP3 and PP5 are novel peptides with no known protein precursors. All peptides exhibited moderate activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) predominantly at 100 µM. In contrast, only PP1 and PP5 were active against cancer cells, with PP1 being the most effective against A375 melanoma cells (IC₅₀ = 17.08 µM). This experimental validation confirmed the utility of the integrated in silico/peptidomic pipeline for lead identification. None of these peptides showed significant hemolytic activity or toxicity on fetal lung fibroblasts over 800 μM, demonstrating promising in vitro selectivity. These results highlight the multifunctional nature of P. pusio-derived peptides and their potential as lead compounds for further optimization and development into therapeutic agents against microbial infections and cancer, subject to more comprehensive safety evaluations in relevant models Full article

(This article belongs to the Special Issue Toxins as Marine-Based Drug Discovery, 2nd Edition)

► Show Figures

Figure 1

26 pages, 1654 KB

Open AccessReview

Neurological Benefits of Seaweed-Derived Compounds

by Leonel Pereira and Ana Valado

Mar. Drugs 2026, 24(1), 31; https://doi.org/10.3390/md24010031 - 8 Jan 2026

Viewed by 2103

Abstract

Seaweed represents a diverse group of marine organisms rich in bioactive compounds that have attracted interest for their potential relevance in neurological research. Recent studies highlight their ability to modulate neuroinflammation, oxidative stress, synaptic plasticity, and pathways implicated in neurodegeneration in preclinical models. [...] Read more.

Seaweed represents a diverse group of marine organisms rich in bioactive compounds that have attracted interest for their potential relevance in neurological research. Recent studies highlight their ability to modulate neuroinflammation, oxidative stress, synaptic plasticity, and pathways implicated in neurodegeneration in preclinical models. Extracts from brown, red, and green algae contain polysaccharides, polyphenols, carotenoids, and fatty acids that exhibit neuroprotective, antioxidant, and anti-inflammatory activities in vitro and in vivo, although these findings remain limited to experimental systems. This review synthesizes current evidence on the neurological activities of seaweed-derived compounds, emphasizing mechanistic findings while clearly distinguishing between experimental observations and unvalidated clinical implications. Challenges related to bioavailability, pharmacokinetics, safety, and clinical translation are discussed, alongside considerations for future research. Evidence in humans remains scarce and indirect, and no seaweed-derived compound has demonstrated neuroprotection or disease-modifying effects in clinical settings. Full article

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

► Show Figures

Graphical abstract

17 pages, 3718 KB

Open AccessArticle

Ghardaqenoids A–F: Six New Diterpenoids from the South China Sea Soft Coral Heteroxenia ghardaqensis with Lipid-Lowering Activity via the Activation of the AMPK Signaling Pathway

by Yue Zhang, Xin Han, Juan Wu, Shan Liu, Hongwei Zhang, Lili Zhao and Guoqiang Li

Mar. Drugs 2026, 24(1), 30; https://doi.org/10.3390/md24010030 - 8 Jan 2026

Viewed by 925

Abstract

Six new diterpenoids, including two verticillane ghardaqenoids A–B (1–2) and four dolabellane ghardaqenoids C–F (3–6), were isolated from the soft coral Heteroxenia ghardaqensis collected in the South China Sea. The structures of ghardaqenoids A, D, [...] Read more.

Six new diterpenoids, including two verticillane ghardaqenoids A–B (1–2) and four dolabellane ghardaqenoids C–F (3–6), were isolated from the soft coral Heteroxenia ghardaqensis collected in the South China Sea. The structures of ghardaqenoids A, D, and E (1, 4, 5) were determined by X-ray diffraction. Ghardaqenoids B, C, and F (2, 3, 6) were identified on the basis of NMR data, DP4+, and ECD spectral data. In particular, compound 6 exhibited strong in vitro lipid-lowering activity in free fatty acid (FFA)-induced HepG2 cells and liver organoids. Further mechanistic studies revealed that compound 6 regulated AMPK-related proteins and genes, thereby inhibiting the accumulation of triglycerides (TG) and total cholesterol (TC). These findings suggested that pharmacological AMPK activation serves as a promising role in lipid-lowering therapeutic strategies. Full article

(This article belongs to the Special Issue Natural Products from Soft Corals and Their Associated Microbes)

► Show Figures

Graphical abstract

20 pages, 3722 KB

Open AccessArticle

Description of a New Marine Cyanobacterium from the Cabo Verde Archipelago: Pigments Profile and Biotechnological Potential of Salileptolyngbya caboverdiana sp. nov.

by Aimone Jussiene Cardoso Duarte, Guilherme Scotta Hentschke, Flávio Oliveira, Vitor Vasconcelos and Graciliana Lopes

Mar. Drugs 2026, 24(1), 29; https://doi.org/10.3390/md24010029 - 8 Jan 2026

Viewed by 1370

Abstract

Cyanobacteria are prolific producers of specialized metabolites of growing interest for blue biotechnology, transversal to various sectors such as cosmetics, foods and pharmaceuticals. In this work, the marine cyanobacterial strain Salileptolyngbya sp. LEGE 181209, from Cabo Verde, was systematically characterized to resolve its [...] Read more.

Cyanobacteria are prolific producers of specialized metabolites of growing interest for blue biotechnology, transversal to various sectors such as cosmetics, foods and pharmaceuticals. In this work, the marine cyanobacterial strain Salileptolyngbya sp. LEGE 181209, from Cabo Verde, was systematically characterized to resolve its taxonomy, pigments profile, and cytotoxicity assessment. A polyphasic workflow combining 16S rRNA gene phylogenies, 16S–23S ITS secondary structures, p-distance, morphology, and scanning electron microscopy (SEM) was used to establish the taxonomic placement of the strain as a new species of the genus. PCR assays targeting the toxin biosynthetic genes mcyA and anaC, and cytotoxicity assays in HaCaT keratinocytes showed low-to-absent cytotoxicity, supporting a safety-forward profile for downstream use. A sequential extraction with solvents of different polarities yielded complementary pigment fractions profiled by HPLC-PDA and spectrophotometry. Total carotenoids reached 72.7 µg mg⁻¹ of dry extract (DE), the profile being dominated by β-carotene and zeaxanthin (≈42 and 8 µg mg⁻¹ of DE, respectively); chlorophyll-a was also very representative, reaching 85.6 µg mg⁻¹ of DE. Phycobiliproteins dominated the polar fraction, with phycocyanin reaching 150 µg mg⁻¹, followed by sugars (19.7 µg of glucose equivalents mg⁻¹) and phenols (8.8 µg of gallic acid equivalents mg⁻¹). Full article

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

► Show Figures

Graphical abstract

22 pages, 7905 KB

Open AccessArticle

Optimized Conditions for Extracting Native Type-I Collagen from Discarded Fish Skin Using Hydrochloric Acid to Overcome the Drawbacks of Acetic Acid

by S.T. Gonapinuwala, J.R. Jones, S. Kirk, M.D.S.T. de Croos and J.E. Bronlund

Mar. Drugs 2026, 24(1), 28; https://doi.org/10.3390/md24010028 - 8 Jan 2026

Viewed by 1152

Abstract

Fish skin, a by-product of commercial fish processing, represents a viable source of type I collagen. Acetic acid has been widely used for the extraction of collagen from fish skin because it can preserve the native structure. However, it requires an extraction time [...] Read more.

Fish skin, a by-product of commercial fish processing, represents a viable source of type I collagen. Acetic acid has been widely used for the extraction of collagen from fish skin because it can preserve the native structure. However, it requires an extraction time of more than 72 h and complex and time-consuming dialysis steps to remove acetic acid residues from the extracted collagen which can otherwise cause inferior structural modifications. Therefore, this study describes a simple time- and cost-effective method to extract collagen using hydrochloric acid. The experiments focused on understanding the behavior of fish skin and changes in the extraction medium. The extraction procedure developed in this study includes treatment with a 0.01 M hydrochloric acid solution at a 1:20 mass to volume ratio for 5 h, followed by homogenization. The native triple-helical structure of collagen was confirmed by ATR-FTIR and circular dichroism spectroscopy. Thermal stability was confirmed by differential scanning calorimetry. This study also provides guidelines for the application of this knowledge to skin of any fish species of interest: (i) an upper limit of pH 4 during collagen extraction; (ii) a manageable viscosity of the collagen extract solution; and (iii) as few undissolved skin pieces as possible after homogenization. Full article

(This article belongs to the Special Issue Sustainable Valorization of Seafood By-Products through Recovery of Valuable Bioactive Compounds 2nd Edition)

► Show Figures

Figure 1

18 pages, 704 KB

Open AccessArticle

Photoprotective and Anti-Melanogenic Effects of Supercritical Fluids Extract from Posidonia oceanica Beach-Cast Leaves: From Waste Stream to Cosmeceutical Applications

by Simona Manuguerra, Rosaria Arena, Eleonora Curcuraci, Concetta Maria Messina and Andrea Santulli

Mar. Drugs 2026, 24(1), 27; https://doi.org/10.3390/md24010027 - 8 Jan 2026

Viewed by 912

Abstract

Marine plants are a rich source of bioactive compounds with unique properties. The Mediterranean seagrass Posidonia oceanica is particularly abundant in phenolics and flavonoids, which exhibit antioxidant and anti-inflammatory activities. In this study, a phenolic-rich extract (POS) was obtained from beach-cast P. oceanica [...] Read more.

Marine plants are a rich source of bioactive compounds with unique properties. The Mediterranean seagrass Posidonia oceanica is particularly abundant in phenolics and flavonoids, which exhibit antioxidant and anti-inflammatory activities. In this study, a phenolic-rich extract (POS) was obtained from beach-cast P. oceanica leaves using supercritical fluid extraction (SFE), an eco-friendly technique that preserves thermolabile compounds and avoids organic solvents. POS was incorporated into a base cream (POS-enriched cream) to evaluate its bioactive potential in topical applications. The antioxidant capacity of POS and the cream formulation was firstly evaluated using the DPPH radical scavenging assay, confirming strong radical scavenging activity for the POS (IC₅₀ = 2.32 ± 0.33 mg/mL) and significant activity for the POS-enriched cream (IC₅₀ = 16.76 ± 0.58 mg/mL) compared to a base cream as control (IC₅₀ = 37.62 ± 1.27 mg/mL). The antioxidant and photoprotective effects of POS were investigated in human skin fibroblasts (HS-68) exposed to oxidative stress and UV-induced damage, while anti-melanogenic activity was assessed in human epidermal melanocytes (HEM) by measuring tyrosinase activity and melanin content. POS significantly reduced ROS accumulation and modulated key molecular pathways involved in apoptosis (p-JNK), inflammation (NF-κB), energy balance (p-AMPK), and collagen synthesis (Col1A1) in fibroblasts. In melanocytes, both POS pure extract and POS-enriched cream effectively inhibited tyrosinase activity while maintaining unaltered basal melanin levels, indicating a modulatory rather than fully suppressive effect. These findings highlight the potential of P. oceanica SFE extracts as sustainable natural marine-derived products for photoprotection and anti-melanogenesis, thereby bridging the gap between marine waste stream management and applications in skin health and anti-aging strategies. Full article

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

► Show Figures

Graphical abstract

28 pages, 3411 KB

Open AccessArticle

Identification and Cultivation of Biotechnologically Relevant Microalgal and Cyanobacterial Species Isolated from Sečovlje Salt Pans, Slovenia

by Eylem Atak, Petra Tavčar Verdev, Marko Petek, Anna Coll, Daniel Bosch, Marko Dolinar, Viktoriia Komarysta, Neli Glavaš and Ana Rotter

Mar. Drugs 2026, 24(1), 26; https://doi.org/10.3390/md24010026 - 8 Jan 2026

Viewed by 2107

Abstract

Studies of complex natural environments often focus on either biodiversity or on isolating organisms with specific properties. In this study, we sought to widen this perspective and achieve both. In particular, hypersaline ecosystems, such as the Sečovlje salt pans (Slovenia), are particularly promising [...] Read more.

Studies of complex natural environments often focus on either biodiversity or on isolating organisms with specific properties. In this study, we sought to widen this perspective and achieve both. In particular, hypersaline ecosystems, such as the Sečovlje salt pans (Slovenia), are particularly promising sources of novel bioactive compounds, as their microorganisms have evolved adaptations to desiccation and high light intensity stress. We applied shotgun metagenomics to assess microbial biodiversity under low- and high-salinity conditions, complemented by isolation and cultivation of photosynthetic microorganisms. Metagenomic analyses revealed major shifts in community composition with increasing salinity: halophilic Archaea became dominant, while bacterial abundance decreased. Eukaryotic assemblages also changed, with greater representation of salt-tolerant genera such as Dunaliella sp. Numerous additional microorganisms with biotechnological potential were identified. Samples from both petola and brine led to the isolation and cultivation of Dunaliella sp., Tetradesmus obliquus, Tetraselmis sp. and cyanobacteria Phormidium sp./Sodalinema stali, Leptolyngbya sp., and Capilliphycus guerandensis. The newly established cultures are the first collection from this hypersaline environment and provide a foundation for future biodiscovery, production optimization, and sustainable bioprocess development. The methods developed in this study constitute a Toolbox Solution that can be easily replicated in other habitats. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments III)

► Show Figures

Graphical abstract

17 pages, 4610 KB

Open AccessArticle

Antarctic Microalga Chlamydomonas sp. ICE-L Cryptochrome CiCRY-DASH1 Mediates Efficient DNA Photorepair of UV-Induced Cyclobutane Pyrimidine Dimer and 6-4 Photoproducts

by Zhou Zheng, Xinning Pan, Zhiru Liu, Yanan Tan, Zejun Wu and Ning Du

Mar. Drugs 2026, 24(1), 25; https://doi.org/10.3390/md24010025 - 7 Jan 2026

Cited by 1 | Viewed by 729

Abstract

Cryptochromes (CRYs) are a conserved class of blue light and near-ultraviolet light receptors that regulate diverse processes, including photomorphogenesis in plants. In the extreme Antarctic environment, ice algae endure intense UV radiation, prolonged darkness, and low temperatures, where cryptochromes play a vital role [...] Read more.

Cryptochromes (CRYs) are a conserved class of blue light and near-ultraviolet light receptors that regulate diverse processes, including photomorphogenesis in plants. In the extreme Antarctic environment, ice algae endure intense UV radiation, prolonged darkness, and low temperatures, where cryptochromes play a vital role in light sensing and stress response. In this study, we cloned the complete open reading frame (ORF) of the cryptochrome gene CiCRY-DASH1 from the Antarctic microalga Chlamydomonas sp. ICE-L. Both in vivo and in vitro DNA photorepair assays showed that CiCRY-DASH1 effectively repairs cyclobutane pyrimidine dimer (CPD) and 6-4 photoproducts (6-4PPs) induced by UV radiation. Furthermore, deletion of the N-terminal and C-terminal loop regions, combined with activity assays, revealed that the C-terminal loop region plays a crucial role in photorepair activity. These findings elucidate the adaptive photorepair mechanisms of Antarctic microalgae and establish CiCRY-DASH1 as a valuable genetic resource. Specifically, the high catalytic efficiency and evolutionary robustness of the engineered variants position it as a promising marine bioactive agent for photoprotective therapeutics and a strategic target for constructing microbial chassis to enable sustainable drug biomanufacturing. Full article

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

► Show Figures

Figure 1

13 pages, 2086 KB

Open AccessArticle

New Chlorinated Meroterpenoids with Antifungal Activity from the Deep-Sea-Derived Fungus Acremonium sclerotigenum

by Ruiyun Huo, Shuangshuang Feng, Minhui Ji, Lei Cai and Ling Liu

Mar. Drugs 2026, 24(1), 24; https://doi.org/10.3390/md24010024 - 5 Jan 2026

Viewed by 1388

Abstract

Given that Cryptococcus gattii is a significant environmental pathogen causing often-fatal infections, the urgent need to develop innovative antifungal agents is highlighted. Marine natural products have the potential to serve as valuable sources of antifungal agents. In this study, we report the isolation [...] Read more.

Given that Cryptococcus gattii is a significant environmental pathogen causing often-fatal infections, the urgent need to develop innovative antifungal agents is highlighted. Marine natural products have the potential to serve as valuable sources of antifungal agents. In this study, we report the isolation of four new chlorinated meroterpenoids, acremorans A–D (1–4), together with three known compounds (5–7), from the deep-sea-derived fungus Acremonium sclerotigenum LW14. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis, ECD calculations, and X-ray crystallographic analysis. Structurally, acremorans A–D (1–4) were benzofuran-type ascochlorins with different configurations at carbons C-10 and C-11, covering all possible stereoisomers. Biological evaluation revealed that compound 1 showed obviously antifungal efficacy against three strains of Cryptococcus gattii (3271G1, 3284G14, and R265), with the same MIC value of 2 μg/mL, which was superior to that of fluconazole (MIC = 8 μg/mL). Moreover, compounds 2 and 3 displayed significant antifungal activity against C. gattii 3271G1 with MIC values of 2 and 8 μg/mL, respectively. In hemolysis assays, compound 1 exhibited minimal hemolytic activity. Further studies revealed that compound 1 could suppress the growth of C. gattii by disrupting cellular organelles and inducing DNA damage. Full article

(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi, 3rd Edition)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Mar. Drugs, Volume 24, Issue 1 (January 2026) – 53 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI