Marine Drugs

16 pages, 662 KB

Open AccessArticle

Bioactivity and in Silico Insights of Collagen-Derived Peptides from Jellyfish (Stomolophus sp. 2) Mesoglea

by Blanca del Sol Villalba-Urquidy, Wilfrido Torres-Arreola, Isabel Medina, Laura Estefany Hernández-Aguirre, Jesús Enrique Chan-Higuera and Josafat Marina Ezquerra-Brauer

Mar. Drugs 2025, 23(11), 427; https://doi.org/10.3390/md23110427 - 5 Nov 2025

Abstract

Jellyfish, a promising source of bioactive compounds, has attracted the attention of the biotechnology sector. This research explored the antioxidant and antimutagenic properties and the genotoxicity of peptides derived from blue cannonball jellyfish (Stomolophus sp. 2) collagen hydrolysates (JCH) as potential food [...] Read more.

Jellyfish, a promising source of bioactive compounds, has attracted the attention of the biotechnology sector. This research explored the antioxidant and antimutagenic properties and the genotoxicity of peptides derived from blue cannonball jellyfish (Stomolophus sp. 2) collagen hydrolysates (JCH) as potential food supplements. Firstly, JCH was fractionated into three parts based on molecular weight. Notably, the low-molecular-weight hydrolyzed fraction (<3 kDa) exhibited the highest bioactivity, with ABTS scavenging activity of 8993 ± 5.2 μmol TE/g and an antimutagenic inhibition rate against AFB₁ of 88%. This fraction remained non-genotoxic at 100 ppm, suggesting its suitability for potential applications without evidence of genotoxic damage. In addition, in silico analysis revealed 15 unique peptides in Stomolophus sp. 2 collagen hydrolysates, ten of which showed particularly promising bioactive potential. Peptides from Stomolophus sp. 2 with molecular weights under 3 kDa exhibit remarkable bioactivity and hold great promise for future research on molecular characterization and bioactive food supplements. Full article

(This article belongs to the Special Issue Marine Bioactive Substances: From By-Products to Innovative Applications)

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20 pages, 3658 KB

Open AccessArticle

Structural Comparison and Therapeutic Effects on Ulcerative Colitis of Fucoidan and Its Derivative from Saccharina japonica

by Yanlei Yu, Xiaoshu Jin, Yunjie Zhao, Ningning Wang, Yi Hua, Youmin Ying, Bin Wei and Hong Wang

Mar. Drugs 2025, 23(11), 426; https://doi.org/10.3390/md23110426 - 3 Nov 2025

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that can lead to intestinal complications and systemic risks, significantly increasing the likelihood of colorectal cancer in individuals with long-term illness. Fucoidan has shown potential in alleviating UC; however, the structure–activity relationship remains [...] Read more.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that can lead to intestinal complications and systemic risks, significantly increasing the likelihood of colorectal cancer in individuals with long-term illness. Fucoidan has shown potential in alleviating UC; however, the structure–activity relationship remains challenging. The present study aims to compare fucoidan (CF) and its degraded derivatives (DF) in the prevention and treatment of UC. Structural analysis demonstrated that CF and DF possess similar monosaccharide compositions and sulfation content; however, they differ significantly in molecular weight, with CF measuring 582 kDa and DF 2.3 kDa. Additionally, DF display a lower degree of branching compared to CF. Results from the mouse model demonstrated that both CF and DF can effectively alleviate clinical symptoms of UC; however, the underlying mechanisms of action are likely to differ. Both CF and DF produced comparable improvements in the disease activity index. CF demonstrated superior efficacy in alleviating weight loss and maintaining colon length, whereas DF showed greater benefits in protecting the colonic mucosa and reducing inflammatory infiltration. The gut microbiota analysis indicated that DF was more effective in restoring microbial diversity in UC mice. Both CF and DF were capable of modulating microbial imbalances at the phylum and genus levels, although the specific taxa exhibited differences. Full article

(This article belongs to the Section Marine Pharmacology)

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17 pages, 2598 KB

Open AccessReview

Integrated Regulation of Immunity and Nutritional Symbiosis in Deep-Sea Mussels

by Akihiro Tame

Mar. Drugs 2025, 23(11), 425; https://doi.org/10.3390/md23110425 - 31 Oct 2025

Abstract

Deep-sea mussels of the genus Bathymodiolus exhibit adaptability to nutrient-poor deep-sea environments by establishing nutritional intracellular symbiosis with chemosynthetic bacteria harbored within the gill epithelial cells. However, this poses a conflict for the innate immune system of the host, which must balance the [...] Read more.

Deep-sea mussels of the genus Bathymodiolus exhibit adaptability to nutrient-poor deep-sea environments by establishing nutritional intracellular symbiosis with chemosynthetic bacteria harbored within the gill epithelial cells. However, this poses a conflict for the innate immune system of the host, which must balance the tolerance of beneficial symbiotic bacteria with the need to eliminate exogenous microbes. This review synthesizes existing knowledge and recent findings on Bathymodiolus japonicus to outline the cellular and molecular mechanisms governing this symbiotic relationship. In the host immune system, hemocytes are responsible for systemic defense, whereas gill cells are involved in local symbiotic acceptance. Central to the establishment of symbiosis is the host’s phagocytic system, which non-selectively engulfs bacteria but selectively retains symbionts. We highlight a series of cellular events in gill cells involving the engulfment, selection, retention and/or digestion of symbionts, and the regulatory mechanism of phagocytosis through mechanistic target of rapamycin complex 1, which connects bacterial nutrient supply with host immune and metabolic responses. This integrated model of symbiosis regulation, which links immunity, metabolism, and symbiosis, provides a fundamental framework for understanding how hosts establish and maintain a stable coexistence with microbes, offering a new perspective on symbiotic strategies in diverse organisms. Full article

(This article belongs to the Special Issue Defying the Odds: Innate Immunity in Invertebrates Living in Deep-Sea Extreme Environments)

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17 pages, 1905 KB

Open AccessArticle

Lipidomic Screening of Marine Diatoms Reveals Release of Dissolved Oxylipins Associated with Silicon Limitation and Growth Phase

by Imanol Ulloa, Jiwoon Hwang, Matthew D. Johnson and Bethanie R. Edwards

Mar. Drugs 2025, 23(11), 424; https://doi.org/10.3390/md23110424 - 31 Oct 2025

Abstract

Marine diatoms are an important group of phytoplankton that can shape marine ecosystems and global carbon cycling. When stressed, either physiologically or by grazing, diatoms release oxidized, lipid-derived signals known as oxylipins. Diatom-derived oxylipins are proposed to serve as defense and signaling chemicals [...] Read more.

Marine diatoms are an important group of phytoplankton that can shape marine ecosystems and global carbon cycling. When stressed, either physiologically or by grazing, diatoms release oxidized, lipid-derived signals known as oxylipins. Diatom-derived oxylipins are proposed to serve as defense and signaling chemicals that affect multiple components of marine ecosystems. Therefore, to elucidate the diversity of diatom-derived oxylipins produced during stress, we profiled the spectrum of dissolved lipids of five diatom species in culture under silicon limitation and across growth phases using ultra-high performance liquid chromatography coupled with high-resolution accurate mass spectrometry. In this study, we present evidence that physiological changes associated with Si-limitation elicit the extracellular release of linear oxygenated fatty acids (LOFAs) across five diatom species. For diatoms like Skeletonema japonicum and Pseudo-nitzschia multiseries, silicon limitation induced a distinct lipidomic signature driven by oxylipins known to be allelopathic. While their lipoxygenases were found to be different, S. japonicum and P. multiseries had the most similar dissolved lipidomes, suggesting alternative controls on oxylipin biosynthesis. Consequently, elevated oxylipin concentrations with silicon stress, estimated up to 5.91 µM, pose implications for diatoms at sea, potentially affecting ecosystems and biogeochemistry. Full article

(This article belongs to the Special Issue Marine Algal Chemical Ecology 2024)

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22 pages, 6134 KB

Open AccessArticle

Novel Sulfated Oligosaccharide DP9 from Marine Algae, Gracilaria lemaneiformis: A Potent Galectin-3 Inhibitor for Pancreatic Cancer Therapy

by Pingting Liu, Fengyuan Li, Zhicong Liu and Yang Liu

Mar. Drugs 2025, 23(11), 423; https://doi.org/10.3390/md23110423 - 30 Oct 2025

Abstract

Galectin-3 (Gal-3) is a histologic marker of pancreatic cancer and a potential therapeutic target. This study aimed to characterize a novel sulfated agarose-derived oligosaccharide (DP9) from marine algae, Gracilaria lemaneiformis, evaluate its Gal-3 inhibitory activity, and investigate its anti-pancreatic cancer mechanisms. Through [...] Read more.

Galectin-3 (Gal-3) is a histologic marker of pancreatic cancer and a potential therapeutic target. This study aimed to characterize a novel sulfated agarose-derived oligosaccharide (DP9) from marine algae, Gracilaria lemaneiformis, evaluate its Gal-3 inhibitory activity, and investigate its anti-pancreatic cancer mechanisms. Through controlled acid hydrolysis, a series of odd-numbered oligosaccharides (DP3-11) were obtained, in which DP9 showed the strongest Gal-3 inhibition in hemagglutination assays. Structural analysis confirmed DP9’s unique composition including an alternating β (1→4)-D-galactose and α (1→3)-3,6-anhydro-L-galactose backbone, featuring partial 6-O-methylation on β-D-galactose and 6-O-sulfation on 3,6-anhydro-α-L-galactose residues. Molecular docking revealed DP9’s binding to Gal-3’s carbohydrate recognition domain through key hydrogen bonds (His158, Arg162, Lys176, Asn179 and Arg186) and hydrophobic interactions (Pro117, Asn119, Trp181 and Gly235), with the sulfate group enhancing binding affinity. In vitro studies demonstrated DP9’s selective anti-pancreatic cancer activity against BxPC-3 cells, including inhibition of cell proliferation; S-phase cell cycle arrest; induction of apoptosis; and suppression of migration and invasion. Mechanistically, DP9 attenuated the Gal-3/EGFR/AKT/FOXO3 signaling pathway while showing minimal cytotoxicity to normal cells. This study first demonstrated that agarose-derived odd-numbered oligosaccharides (DP9) can serve as effective Gal-3 inhibitors, which proved its potential as a marine oligosaccharide-based therapeutic agent for pancreatic cancer. Full article

(This article belongs to the Special Issue Marine-Derived Bioactive Substances and Their Mechanisms of Action)

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10 pages, 939 KB

Open AccessArticle

Cembrane-Based Diterpenoids Isolated from the Soft Coral Sarcophyton sp.

by Yueping Wang, Xiaohui Li, Yusen Guo, Te Li, Xia Yan, Han Ouyang, Wenhan Lin, Bin Wu, Hongyu Hu and Shan He

Mar. Drugs 2025, 23(11), 422; https://doi.org/10.3390/md23110422 - 30 Oct 2025

Abstract

This research explored the chemical composition of the soft coral Sarcophyton sp., leading to the discovery of six previously unreported cembranoids, sarcophynoids D–I (1–6), and three known analog compounds (7–9). Structural elucidation of the new [...] Read more.

This research explored the chemical composition of the soft coral Sarcophyton sp., leading to the discovery of six previously unreported cembranoids, sarcophynoids D–I (1–6), and three known analog compounds (7–9). Structural elucidation of the new metabolites was achieved by spectroscopic methods, including one- and two-dimensional (1D and 2D) NMR (COSY, HSQC and HMBC), high-resolution electrospray ionization mass spectrometry (HRESIMS), quantum mechanical NMR (QM-NMR) methods, electronic circular dichroism (ECD) calculations, and comparison with literature data. All isolated substances were screened for antibacterial activities, and most exhibited moderate inhibitory effects against six pathogenic bacterial strains, with MIC values between 8 and 64 μg/mL. In addition, the effects of these compounds on LPS and IFN-γ stimulated RAW264.7 cells, focused on the release of NO and TNF-α, were also evaluated, but were inactive at 20 μM. Full article

(This article belongs to the Special Issue Marine Natural Products with Antimicrobial Activity)

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25 pages, 6319 KB

Open AccessArticle

Obtainment of Two Monomorphic Nematocysts from Nemopilema nomurai (Cnidaria: Scyphozoa) and Comparative Analysis of the Biological Activities of Their Contents

by Yongfei Lyu, Yichao Huang, Juxingsi Song, Dayuan Zhou, Shuaijun Zou, Jie Li, Fan Wang, Qianqian Wang, Yanan Hu, Shaoqian Zhu, Sai Luo, Xinyue Gan, Liming Zhang and Guoyan Liu

Mar. Drugs 2025, 23(11), 421; https://doi.org/10.3390/md23110421 - 30 Oct 2025

Abstract

Nemopilema nomurai is a species of common large toxic jellyfish in China seas, and its tentacle tissues contain various types of nematocysts. However, the correlation between the morphology and function of nematocysts still remains unclear. In this study, we first obtained two monomorphic [...] Read more.

Nemopilema nomurai is a species of common large toxic jellyfish in China seas, and its tentacle tissues contain various types of nematocysts. However, the correlation between the morphology and function of nematocysts still remains unclear. In this study, we first obtained two monomorphic nematocysts with high-purity from N. nomurai, namely Anisorhizas and O-isorhizas, by density gradient centrifugation: the Anisorhizas is small and rod-shaped and the O-isorhizas is larger and spherical. Upon deionized water stimulation, O-isorhizas exhibited a stronger discharge capability than Anisorhizas. The nematocyst contents of Anisorhizas (AnC) and O-isorhizas (OnC) were extracted separately, and their composition and bioactivities were analyzed simultaneously. The protein bands by SDS-PAGE revealed similar distributions in AnC and OnC, except that the protein band distribution in OnC was more extensive. OnC showed stronger cytotoxicity, hemolytic activity, metalloprotease activity, and serine protease activity than AnC. In contrast, AnC exhibited a higher antioxidant activity and significant proinflammatory activity. Both AnC and OnC exhibited antimicrobial activities against certain marine pathogenic Vibrios. These results suggest that O-isorhizas, with the larger capsule capability, stronger discharge ability and toxicity, likely plays a major role in inducing toxic effects and tissue damage, while Anisorhizas, being smaller and less toxic, may undertake preferentially other functions, such as synergistic predation, environmental stress adaptation, and energy balance maintenance. This study provides insights into the morpho-functional relationship between various types of nematocysts, and also lays a foundation for further exploration of the functional diversity of nematocysts and the mechanisms underlying jellyfish envenomation. Full article

(This article belongs to the Special Issue Jellyfish-Derived Compounds)

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18 pages, 1714 KB

Open AccessArticle

Phytochemicals and Bioactivities of the Halophyte Sea Mayweed (Tripleurospermum maritimum L.)

by Clément Lemoine, Maria João Rodrigues, Xavier Dauvergne, Stéphane Cérantola, Luísa Margarida Batista Custódio and Christian Magné

Mar. Drugs 2025, 23(11), 420; https://doi.org/10.3390/md23110420 - 30 Oct 2025

Abstract

Sea mayweed (Tripleurospermum maritimum L. syn. Matricaria maritima) is a halophytic species widely distributed along the Atlantic shoreline. Unlike other Tripleurospermum species, the chemical composition and biological activities of this halophyte have received no attention. Here, a hydroalcoholic extract of sea [...] Read more.

Sea mayweed (Tripleurospermum maritimum L. syn. Matricaria maritima) is a halophytic species widely distributed along the Atlantic shoreline. Unlike other Tripleurospermum species, the chemical composition and biological activities of this halophyte have received no attention. Here, a hydroalcoholic extract of sea mayweed leaves was evaluated for in vitro antioxidant (DPPH, ABTS, and FRAP bioassays), anti-inflammatory (NO reduction in RAW 264.7 macrophages), anti-diabetic (alpha-glucosidase inhibition), neuroprotective (inhibition of acetylcholinesterase), and skin protective (tyrosinase, melanogenesis, elastase, and collagenase inhibition) activities. Solid–liquid partition chromatography of the extract and NMR characterization of its fractions allowed the identification of some major compounds, including fructo-oligosaccharides in the MeOH_20% fraction, a new carbohydrate called tripleurospermine (1), 3-5-dicaffeoylquinic acid (2) in the MeOH_40% fraction, and matricaria lactone (3) in the MeOH_80% fraction. MeOH₄₀ fraction exhibited strong antioxidant, anti-tyrosinase (thus skin-whitening potential), and anti-glycosidase activities (anti-diabetic potential), whereas MeOH_80% fraction showed anti-inflammatory and anti-diabetic potential. Overall, our results suggest that sea mayweed may have dietary or medicinal uses due to its biochemical composition and bioactivities. Full article

(This article belongs to the Special Issue Bioactive Specialized Metabolites from Marine Plants)

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21 pages, 3952 KB

Open AccessArticle

Creating an Improved Diatoxanthin Production Line by Knocking Out CpSRP54 in the zep3 Background in the Marine Diatom Phaeodactylum tricornutum

by Charlotte Volpe, Zdenka Bartosova, Ralph Kissen, Per Winge and Marianne Nymark

Mar. Drugs 2025, 23(11), 419; https://doi.org/10.3390/md23110419 - 29 Oct 2025

Abstract

Diatoxanthin is a photoprotective carotenoid found in a few groups of microalgae displaying in vitro anti-inflammatory and anti-cancer properties, making it a promising candidate for nutraceutical, pharmaceutical, and cosmetic applications. However, large-scale production is currently nonexistent because of two major challenges: Instability during [...] Read more.

Diatoxanthin is a photoprotective carotenoid found in a few groups of microalgae displaying in vitro anti-inflammatory and anti-cancer properties, making it a promising candidate for nutraceutical, pharmaceutical, and cosmetic applications. However, large-scale production is currently nonexistent because of two major challenges: Instability during microalgae harvesting, where diatoxanthin is rapidly converted back to its inactive precursor diadinoxanthin under non-stressful light conditions, and dependence on prolonged exposure to high-intensity light, which is costly and technically challenging during indoor high-cell-density cultivation. The first limitation was previously addressed by knocking out zeaxanthin epoxidase 3 (ZEP3) in the marine diatom Phaeodactylum tricornutum, resulting in a mutant that stabilized diatoxanthin under non-stressful light conditions. Here, we report an improved diatoxanthin production line where both of the described challenges have been overcome. This was achieved by creating P. tricornutum mutants where the phenotype of the zep3 mutant was combined with the light-sensitive phenotype of the chloroplast signal recognition particle 54 (cpsrp54) mutant. Growth rates were maintained at wild-type levels at light intensities ≤ 150 µmol photons m⁻² s⁻¹ in the zep3cpsrp54 mutants, but prolonged medium light exposure resulted in a 1.5- and 7-fold increase in diatoxanthin concentration compared with zep3 and wild-type, respectively. When returned to low light, the zep3cpsrp54 cultures retained ~80% of their accumulated diatoxanthin. The improved production lines allow for diatoxanthin accumulation without the use of high-intensity light and with limited loss of diatoxanthin when returned to non-stressful light conditions. Full article

(This article belongs to the Special Issue High-Value Algae Products, 2nd Edition)

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15 pages, 3092 KB

Open AccessArticle

Starfish-Derived Extracts Enhance Mitophagy and Suppress Senescence-Associated Markers in Human Dermal Fibroblasts

by Hyun Jung Lee, Junhee Kim, Bada Won, Dong Hun Lee and Ok Sarah Shin

Mar. Drugs 2025, 23(11), 418; https://doi.org/10.3390/md23110418 - 27 Oct 2025

Abstract

While the starfish species Asterias pectinifera (Ap) and Asterias amurensis (Aa) are considered ecological threats to marine environments and the fishing industry, recent studies have identified them as rich sources of highly water-soluble, non-toxic collagen peptides. Mitochondrial dysfunction is [...] Read more.

While the starfish species Asterias pectinifera (Ap) and Asterias amurensis (Aa) are considered ecological threats to marine environments and the fishing industry, recent studies have identified them as rich sources of highly water-soluble, non-toxic collagen peptides. Mitochondrial dysfunction is a key driver of cellular senescence and skin aging, yet the therapeutic potential of marine-derived extracts in modulating mitophagy remains largely unexplored. In this study, we investigated whether starfish-derived extracts could mitigate senescence-associated phenotypes in human dermal fibroblasts (HDFs) through the modulation of mitophagy. Treatment with Ap- or Aa-derived extracts led to reduced senescence-associated β-galactosidase (SA-β-gal) activity, decreased expression of matrix metalloproteinase-1 (MMP-1), and suppression of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-8 (IL-8). Ap- or Aa-derived extracts significantly increased mitophagy in HDFs stably expressing mitochondrial-targeted Keima (HDF-mtKeima), while knockdown of PINK1, the essential regulator of mitophagy, abolished the mitophagy-inducing effects of Ap- or Aa-treatment, indicating that Ap- or Aa-derived extracts activate PINK1/Parkin-dependent mitophagy pathways. Importantly, PINK1 knockdown reversed starfish-induced suppression of MMP-1 and p21, demonstrating its crucial role in regulating senescence-associated gene expression. Additionally, Ap or Aa treatments significantly reduced reactive oxygen species (ROS) accumulation, improved mitochondrial function, and enhanced both basal and maximal respiratory capacity in senescent HDFs. These findings highlight that extracts derived from starfish promote mitophagy through PINK1-dependent mechanisms, exhibiting significant anti-senescence effects in HDFs. This suggests their potential application in the development of novel cosmeceuticals with skin-protective and rejuvenating properties. Full article

(This article belongs to the Special Issue Marine Natural Products with Skin Health-Promoting Properties)

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22 pages, 9751 KB

Open AccessArticle

Metabolomic Insights into the Phytochemical Profiles and Seasonal Shifts of Fucus serratus and F. vesiculosus Harvested in Danish Coastal Waters (Aarhus Bay)—An Untargeted High-Resolution Mass-Spectrometry Approach

by Mihai Victor Curtasu, Jørgen Ulrik Graudal Levinsen, Annette Bruhn, Mette Olaf Nielsen and Natalja P. Nørskov

Mar. Drugs 2025, 23(11), 417; https://doi.org/10.3390/md23110417 - 26 Oct 2025

Abstract

This study investigated the year-round metabolomic variation in Fucus serratus (FS) and F. vesiculosus (FV) collected monthly from Danish coastal water around Aarhus Bay. Untargeted high-resolution liquid chromatography–mass spectrometry profiling (LC-HRMS), combined with multivariate data analysis and temporal clustering analysis, revealed that species [...] Read more.

This study investigated the year-round metabolomic variation in Fucus serratus (FS) and F. vesiculosus (FV) collected monthly from Danish coastal water around Aarhus Bay. Untargeted high-resolution liquid chromatography–mass spectrometry profiling (LC-HRMS), combined with multivariate data analysis and temporal clustering analysis, revealed that species identity was the primary driver of metabolic separation, followed by seasonal variation. FS showed higher levels of hydrolyzable tannins, flavonoid derivatives, aromatic amino acids, and glutamine-rich peptides, whereas FV was enriched in complex phlorotannins, tricarboxylic acid cycle intermediates, and carnitine derivatives. Temporal analysis identified recurring seasonal patterns across both species, including spring increases in amino acids, purine metabolites, and osmolytes; mid-summer peaks in mannitol and sulfated derivatives; and late-autumn elevations in phenolic compounds and betaine-type osmolytes. Despite apparent interspecific differences, several metabolite groups exhibited similar seasonal dynamics, suggesting shared physiological strategies associated with growth activation in spring, metabolic adjustment during summer to possible increased grazing pressure, and nutrient reallocation prior to winter. These findings provide a comprehensive, high-resolution view of seasonal metabolomic patterns in Fucus spp., offering new insights into their biochemical ecology and supporting the targeted utilization of these species for applications requiring specific metabolite profiles. Finally, this study contributes to the creation or expansion of metabolomic libraries for HRMS specific to Fucus seaweeds. Full article

(This article belongs to the Special Issue Omics Approaches in Marine Compound Discovery)

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10 pages, 2638 KB

Open AccessArticle

Montagnulans A–D with Anti-Osteoclastogenic Activity from the Marine Fungus Montagnula sp. GXIMD 02514

by Miaoping Lin, Humu Lu, Jiaxi Wang, Huangxue Qin, Xinya Xu, Chenghai Gao, Yonghong Liu, Yanhui Tan and Xiaowei Luo

Mar. Drugs 2025, 23(11), 416; https://doi.org/10.3390/md23110416 - 25 Oct 2025

Abstract

Four novel tetramic acid compounds, montagnulans A–D (1–4), were obtained from the Beibu Gulf coral-associated fungus Montagnula sp. GXIMD 02514. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations were accomplished by ECD calculations. [...] Read more.

Four novel tetramic acid compounds, montagnulans A–D (1–4), were obtained from the Beibu Gulf coral-associated fungus Montagnula sp. GXIMD 02514. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations were accomplished by ECD calculations. Structurally, compounds 1–4 were rare leucine-derived tetramic acids bearing an ethyl (1–3) or hexylenic alcohol (4) side chain and a pyranone ring at C-3 of the 2,4-pyrrolidinedione core. Compound 1 exhibited inhibition of lipopolysaccharide (LPS)-induced NF-κB in RAW 264.7 macrophages at 20 μM, which further inhibited RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophages cells (BMMs). This is the first report of osteoclastogenesis inhibitions for tetramic acids, which sheds light on their development as potential osteoclast differentiation inhibitors. Full article

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

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30 pages, 2794 KB

Open AccessReview

Therapeutic Potential of Neopyropia yezoensis: An Updated Review

by Anshul Sharma, Na Young Yoon and Hae-Jeung Lee

Mar. Drugs 2025, 23(11), 415; https://doi.org/10.3390/md23110415 - 23 Oct 2025

Abstract

Neopyropia (N.) yezoensis is a widely cultivated red alga in East Asia and valued worldwide for its rich bioactive constituents recognized for their health benefits, including polsaccharides, porphyrans, pigments, phenolic compounds, phycobiliproteins, polyunsaturated fatty acids, myosporin-like amino acids, and both synthetic [...] Read more.

Neopyropia (N.) yezoensis is a widely cultivated red alga in East Asia and valued worldwide for its rich bioactive constituents recognized for their health benefits, including polsaccharides, porphyrans, pigments, phenolic compounds, phycobiliproteins, polyunsaturated fatty acids, myosporin-like amino acids, and both synthetic and recombinant peptides. This review summarizes the current knowledge regarding the therapeutic potential of N. yezoensis extracts and their bioactive compounds. Based on in vitro, ex vitro, and in vivo experimental data (including those on Drosophila melanogaster larvae), this review comprehensively discusses its antioxidant, anti-inflammatory, neuroprotective, anti-atopic dermatitis, anti-colitis, anticancer, anti-aging, anti-atrophy, metabolic health-promoting effects, improving renal health, proliferating, anti-osteoarthritic, anti-allergic, antibacterial, and antivirus activities. The prebiotic effect of N. yezoensis porphyran through modulation of the gut microbiota was also investigated. Studies have indicated that protein hydrolysates and peptides derived from N. yezoensis with low molecular weights and aromatic and/or hydrophobic amino acids contribute significantly to these diverse bioactivities. Although N. yezoensis has shown promising bioactivity in preclinical models, validated clinical data in humans are currently lacking. Future research should prioritize the design and implementation of well-controlled human clinical trials to fully explore their therapeutic potential. Full article

(This article belongs to the Special Issue Bioactive Specialized Metabolites from Marine Plants)

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16 pages, 4650 KB

Open AccessArticle

5Z-7-Oxozeanol Isolated from the Fungus Curvularia sp. MDCW-1060 Inhibits the Proliferation of MDA-MB-231 Cells via the PI3K-Akt and MAPK Pathways

by Hong Zhang, Jianjian Wang, Chang Xu, Kai Liu, Jufang Xie, Zhoucheng He, Yonghong Liu, Cong Wang and Xinjian Qu

Mar. Drugs 2025, 23(11), 414; https://doi.org/10.3390/md23110414 - 23 Oct 2025

Abstract

The discovery of novel marine natural products and their sustainable application continue to be vital focuses in marine biological research. The aim of this study is to investigate the inhibitory effect of the compound 5Z-7-Oxozeaenol isolated from the fungus Curvularia sp. MDCW-1060 on [...] Read more.

The discovery of novel marine natural products and their sustainable application continue to be vital focuses in marine biological research. The aim of this study is to investigate the inhibitory effect of the compound 5Z-7-Oxozeaenol isolated from the fungus Curvularia sp. MDCW-1060 on the proliferation of MDA-MB-231 cells and its molecular mechanism. A series of functional assays, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, Transwell migration, and colony formation, were employed to evaluate the effects of 5Z-7-Oxozeaenol on cellular viability, apoptosis, migration, and clonogenicity. The RNA sequencing (RNA-seq) coupled with bioinformatic analysis was conducted to identify affected differentiated gene expression and signaling pathways. The molecular docking was performed to predict potential protein targets, and Western blot was used to validate expression and phosphorylation levels of key signaling molecules. The results demonstrated that 5Z-7-Oxozeaenol significantly suppressed proliferation and migration while promoting apoptosis in MDA-MB-231 cells. The transcriptomic analysis indicated enrichment in pathways related to cancer, cytokine–cytokine receptor interaction, MAPK and PI3K-Akt signaling, and cell adhesion molecules. The molecular docking suggested a high binding affinity between 5Z-7-Oxozeaenol and PTPRN. While Western blot analysis confirmed the downregulation of phosphorylated FAK, PI3K, Akt, and MAPK, along with reduced cyclin D1 expression. Additionally, 5Z-7-Oxozeaenol upregulated the pro-apoptotic proteins p53 and cleaved caspase-3. In conclusion, 5Z-7-Oxozeaenol exerts potent antitumor effects on MDA-MB-231 cells through multi-pathway inhibition and induction of apoptosis, highlighting its potential as a marine-derived therapeutic candidate for breast cancer treatment. Full article

(This article belongs to the Special Issue Marine Compounds as Inhibitors)

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15 pages, 6179 KB

Open AccessArticle

Identifying a Marine-Derived Small-Molecule Nucleoprotein Inhibitor Against Influenza A Virus

by Zihan Wang, Yang Zhang, Shangjie Xu, Lishan Sun, Hongwei Zhao and Wei Wang

Mar. Drugs 2025, 23(11), 413; https://doi.org/10.3390/md23110413 - 23 Oct 2025

Abstract

Influenza A virus (IAV) poses a major threat to global public health, exerting immense pressure on human health and the economy. The IAV nucleoprotein (NP) is an ideal target for antiviral drug development. Through Mini-genome and Surface Plasmon Resonance assays, this study discovered [...] Read more.

Influenza A virus (IAV) poses a major threat to global public health, exerting immense pressure on human health and the economy. The IAV nucleoprotein (NP) is an ideal target for antiviral drug development. Through Mini-genome and Surface Plasmon Resonance assays, this study discovered and verified that mycophenolic acid methyl ester (MAE), a secondary metabolite produced by the marine algal-associated fungus Phaeosphaeria spartinae, can target the viral nucleoprotein to exert anti-IAV activity. Pull-down assays and immunofluorescence have revealed that MAE blocks the nuclear import of viral ribonucleoprotein complexes (vRNP) by interfering with the interaction between NP and IMP-α. It also affects the vRNP assembly process by regulating NP oligomerization and the interaction between NP and PB2. In addition, Sandwich ELISA and Electron Microscopy experiments showed that MAE can also inactivate viral particles to reduce the risk of infection. Comprehensive research results indicate that MAE exerts its effects by inhibiting the viral NP protein, which has laid an important foundation for the development of marine-derived NP-targeted drugs. Full article

(This article belongs to the Special Issue Marine Compounds as Inhibitors)

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26 pages, 3924 KB

Open AccessReview

Seaweed Polysaccharides: A Rational Approach for Food Safety Studies

by João Cotas, Mariana Lourenço, Artur Figueirinha, Ana Valado and Leonel Pereira

Mar. Drugs 2025, 23(11), 412; https://doi.org/10.3390/md23110412 - 22 Oct 2025

Abstract

Marine macroalgae (seaweed) are a rich source of bioactive polysaccharides such as agar, carrageenan, and alginate. These three compounds are classified as food additive ingredients, widely used as gelling, thickening, stabilizing, and emulsifying agents in the food, nutraceutical, pharmaceutical, and cosmetic industries. However, [...] Read more.

Marine macroalgae (seaweed) are a rich source of bioactive polysaccharides such as agar, carrageenan, and alginate. These three compounds are classified as food additive ingredients, widely used as gelling, thickening, stabilizing, and emulsifying agents in the food, nutraceutical, pharmaceutical, and cosmetic industries. However, the growing concern for a safer world has sparked renewed interest in their safety evaluation. Unlike synthetic compounds with specified structures, seaweed polysaccharides exhibit substantial structural heterogeneity due to variations in species, habitat, and processing, affecting bioactivity, digestibility, and interactions within the gastrointestinal tract. Although the safety of these compounds is generally accepted, there are still significant gaps in our understanding of their physicochemical behaviour. This highlights the need to develop a standardized digestion model to ensure their safety and evaluate their potential long-term health effects. Most of these compounds are only partially absorbed in the upper gastrointestinal tract, where they are fermented into metabolites with varying health effects. The safety of carrageenan, in particular, remains a subject of debate due to ambiguous results reported by various researchers’ groups. This review highlights the importance of adopting standardized digestion assays, integrated analytical tools, and multidisciplinary approaches. These are crucial for thoroughly evaluating the molecular integrity, metabolism, and biological impact of seaweed polysaccharides, which will ultimately support evidence-based regulatory frameworks and ensure their safe use in human nutrition. This critical analysis focuses on food safety and security, with a methodology that can be applied to other foods or compounds. Full article

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

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24 pages, 2295 KB

Open AccessArticle

Sea Cucumber (Isostichopus badionotus): Bioactivity and Wound Healing Capacity In Vitro of Small Peptide Isolates from Digests of Whole-Body Wall or Purified Collagen

by Leticia Olivera-Castillo, George Grant, Oscar Medina-Contreras, Honorio Cruz-López, Leydi Carrillo-Cocom, Ariadnna Cruz-Córdova, Frank Segura-Cadiz, Daniel Alejandro Fernández-Velasco, Sergio Rodríguez-Morales, Juan Valerio Cauich-Rodríguez, Rosa Esther Moo-Puc, César Puerto-Castillo, Gabriela de Jesus Moo-Pech, Jonatan Jafet Uuh-Narvaez, Miguel Angel Olvera-Novoa and Rossanna Rodriguez-Canul

Mar. Drugs 2025, 23(11), 411; https://doi.org/10.3390/md23110411 - 22 Oct 2025

Abstract

Low-molecular-weight peptides derived from the digestion of body wall proteins in some sea cucumber species have wound-healing and health-promoting properties, but their potency varies widely by species, growth environment, age, and season. For the first time, small peptide (1–3 kDa) fractions have been [...] Read more.

Low-molecular-weight peptides derived from the digestion of body wall proteins in some sea cucumber species have wound-healing and health-promoting properties, but their potency varies widely by species, growth environment, age, and season. For the first time, small peptide (1–3 kDa) fractions have been isolated from the whole-body wall of the sea cucumber Isostichopus badionotus and its constituent collagen and tested for wound healing capacity in vitro. Ultrafiltered digests (1–3 kDa) of the pure collagen, as well as 1–3 kDa digests of the whole-body wall, had potent antioxidant activities and promoted rapid wound healing in a keratinocyte scratch wound assay. Gene expression studies suggested that the wound-healing actions of the individual collagen and body wall 1–3 kDa fractions differed significantly. Low-molecular-weight peptides derived from I. badionotus collagen did promote wound healing in vitro; however, their efficacy may have been modulated by additional factors produced during body wall or collagen digestion. These findings need to be confirmed in vivo. Full article

(This article belongs to the Special Issue Collagen and Chitin from Marine Resources and Their Interdisciplinary Applications—2nd Edition)

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13 pages, 2887 KB

Open AccessArticle

Cellulose and Cellulose Synthase in a Marine Pseudomonas Strain from Antarctica: Characterization, Adaptive Implications, and Biotechnological Potential

by Maria Chiara Biondini, Martina Di Sessa, Alberto Vassallo, Federica Chiappori, Marco Zannotti, Alessio Mancini, Rita Giovannetti and Sandra Pucciarelli

Mar. Drugs 2025, 23(10), 410; https://doi.org/10.3390/md23100410 - 21 Oct 2025

Abstract

Antarctic microorganisms have developed extraordinary strategies for adaptation. They have also demonstrated the ability to produce various biopolymers in response to environmental stress. The demand for biopolymers is constantly increasing and is expected to grow further. Among emerging biomaterials, bacterial cellulose (BC) is [...] Read more.

Antarctic microorganisms have developed extraordinary strategies for adaptation. They have also demonstrated the ability to produce various biopolymers in response to environmental stress. The demand for biopolymers is constantly increasing and is expected to grow further. Among emerging biomaterials, bacterial cellulose (BC) is generating significant interest due to its unique characteristics that distinguish it from plant-based cellulose. BC exhibits higher purity, water-holding capacity, and tensile strength compared to its plant-based counterpart. Furthermore, BC can be obtained through environmentally friendly protocols. Several bacterial strains have already been identified as cellulose producers, including Komagataeibacter xylinus. In this study, a marine bacterial strain named Pseudomonas sp. ef1, isolated from a consortium associated with the Antarctic ciliate Euplotes focardii, was tested for cellulose production. We found that this Antarctic Pseudomonas can produce BC in conditions that appear unique to this bacterial strain. Furthermore, the final BC product is structurally different from that obtained from the well-known BC producer Komagataeibacter xylinus. Additionally, a putative cellulose synthase was identified from the Pseudomonas sp. ef1 genome, exhibiting unique characteristics that may account for the unique BC production capability of this Antarctic marine Pseudomonas. The versatility of BC opens numerous applications, including in papermaking, food, pharmaceutical, and biomedical sectors. Full article

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

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19 pages, 2531 KB

Open AccessArticle

High-Seas Marine Microorganism Delivers an Extract That Dampens LPS-Driven Pro-Inflammatory Signaling: Galbibacter orientalis Strain ROD011

by Minji Kim, You-Jin Jeon, Bomi Ryu, Young-Mog Kim, Jae-Il Kim, Minkyeong Choi, Sohee Kim, Jihye Lee and Jimin Hyun

Mar. Drugs 2025, 23(10), 409; https://doi.org/10.3390/md23100409 - 18 Oct 2025

Abstract

An ethyl acetate extract from the deep-sea bacterium Galbibacter orientalis strain ROD011 (GOEE), collected from international waters, was investigated as a potential anti-inflammatory agent. In lipopolysaccharide (LPS)-stimulated murine macrophages, nitric oxide (NO) production fell by 72–87% at 5–20 µg/mL GOEE without detectable cytotoxicity. [...] Read more.

An ethyl acetate extract from the deep-sea bacterium Galbibacter orientalis strain ROD011 (GOEE), collected from international waters, was investigated as a potential anti-inflammatory agent. In lipopolysaccharide (LPS)-stimulated murine macrophages, nitric oxide (NO) production fell by 72–87% at 5–20 µg/mL GOEE without detectable cytotoxicity. Cyclooxygenase-2 (COX-2 protein abundance decreased in a dose-dependent manner and was nearly absent at 20 µg/mL. In zebrafish embryos, survival was maintained up to 40 µg/mL, and LPS-induced signals were attenuated; the cell-death rate declined from 10 µg/mL onward, and at 20 µg/mL GOEE, reactive oxygen species (ROS) and NO decreased by 85% and 27%, respectively. To explain these effects, untargeted metabolomics with pathway enrichment and network mapping were performed in LPS-driven macrophages. Of the 58 KEGG pathways evaluated, 18 reached significance, notably purine and pyrimidine metabolism, vitamin B6 metabolism, and the one-carbon pool via folate. Coordinated shifts also involved amino-acid/tricarboxylic acid (TCA)-cycle linkages, glutathione and glyoxylate/dicarboxylate, and sphingolipid pathways. Network analysis identified hubs that were concomitantly reprogrammed. Collectively, GOEE achieved multi-level suppression of inflammatory outputs while preserving viability, and the metabolomic signature provides a mechanistic scaffold for its action. These findings nominate a deep-sea microbial extract as a promising anti-inflammatory lead and motivate fractionation and targeted validation of the highlighted metabolic nodes. Full article

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

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