Marine Drugs

15 pages, 3992 KiB

Open AccessArticle

The Mediterranean Sea on the Bench: Unveiling the Marine Invertebrate Sidnyum elegans as a Source of Novel Promising Therapeutic Tools Against Triple-Negative Breast Cancer

by Marcello Casertano, Camilla Esposito, Ivana Bello, Martina Barile, Luana Izzo, Emma Mitidieri, Raffaella Sorrentino, Marialuisa Menna, Elisabetta Panza, Concetta Imperatore and Roberta d’Emmanuele di Villa Bianca

Mar. Drugs 2025, 23(5), 195; https://doi.org/10.3390/md23050195 - 29 Apr 2025

Abstract

This study aims to unveil the marine invertebrate Sidnyum elegans, a Mediterranean ascidian, as a natural resource for the early development of new treatments for triple-negative breast cancer (TNBC). Nine different fractions obtained via medium-pressure liquid chromatography (MPLC) of the butanol-soluble [...] Read more.

This study aims to unveil the marine invertebrate Sidnyum elegans, a Mediterranean ascidian, as a natural resource for the early development of new treatments for triple-negative breast cancer (TNBC). Nine different fractions obtained via medium-pressure liquid chromatography (MPLC) of the butanol-soluble material of the ascidian were evaluated in proliferating MDA-MB-231 cells in a range of 10–50 µg/mL. Among them, the SEB-5 fraction was found to be the most effective in reducing cell proliferation and concomitantly inducing apoptosis, revealed via MTT assay and FACS analysis using Annexin V/PI dual staining. Furthermore, we investigated the effect of this fraction on cell cycle phases, revealing that SEB-5 can arrest the cells in the G0/G1 phase. This latter effect was then confirmed via transcriptomic analysis, showing that treatment with SEB-5 reduced the expression of cyclinB1, CDC25a, and CDK1. Finally, to evaluate the potential antimetastatic effect of SEB-5, a wound-healing assay was performed showing the ability of SEB-5 to reduce MDA-MB-231 cell migration. The chemical characterization of SEB-5 components was performed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS) and nuclear magnetic resonance (NMR) spectroscopy. This analysis revealed the presence of a terpenoid and polyketide-like compounds, including the alkyl sulfate 1 and phosphoeleganin 2, along with three novel phosphoeleganin-related products 3–5. Full article

(This article belongs to the Special Issue Perspectives for the Development of New Multitarget Marine Drugs)

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20 pages, 5265 KiB

Open AccessArticle

Isolation and Characterization of L-Asparaginase-Producing Bacteria from the Arabian–Persian Gulf Region: First Report on Bacillus xiamenensis ASP-J1-4 as a Producer and Its Potential Application

by Ghofran M. Al-Harbi, Essam Kotb, Abeer A. Almiman, Mahmoud M. Berekaa, Salwa Alhamad, Nada F. Alahmady, Meneerah A. Aljafary, Nadiyah M. Alqazlan, Reem I. Alyami, Joud M. Alqarni and Ebtesam Abdullah Al-Suhaimi

Mar. Drugs 2025, 23(5), 194; https://doi.org/10.3390/md23050194 - 29 Apr 2025

Abstract

L-asparaginase (L-ASNase) functions as a chemotherapeutic enzyme with antitumor properties. It facilitates the degradation of L-asparagine (L-ASN), a vital amino acid required for the proliferation of tumor cells. In this study, we have isolated 177 L-ASNase-producing strains from the aquatic environment of the [...] Read more.

L-asparaginase (L-ASNase) functions as a chemotherapeutic enzyme with antitumor properties. It facilitates the degradation of L-asparagine (L-ASN), a vital amino acid required for the proliferation of tumor cells. In this study, we have isolated 177 L-ASNase-producing strains from the aquatic environment of the Arabian–Persian Gulf. The most potent isolate, ASP-J1-4, was an endophyte recovered from the seablite Suaeda maritima and was molecularly identified as B. xiamenensis (accession number PQ593941). The enzyme purified through DEAE-Sepharose displayed a molecular weight of 37 kDa based on the SDS-PAGE profile and lacked detectable L-glutaminase (L-GTNase) activity. Optimal enzyme activity was at 40 °C and pH 9.0, with stability at pH 7–9. The maximum stimulation effect was found in the presence of Fe³⁺, Mn²⁺, and Na⁺ ions, respectively. The enzyme demonstrated a V_max of 35.71 U/mL and a K_m of 0.15 mM. Interestingly, ASP-J1-4 L-ASNase showed a dose-dependent inhibition against human colon carcinoma (HCT-116) and cervical Henrietta Lacks (HeLa) cell lines, with IC₅₀ values of 15.42 µg/mL and 12.13 µg/mL, respectively. These findings collectively suggest a biocompatible, efficient, and robust enzyme for potential applications in tumor therapy after validation of in vivo studies and clinical trials. This study introduces the first deep screening program for L-ASNase-producing bacteria harboring in the Arabian–Persian Gulf region. In addition, it launches B. xiamenensis and other species as new sources of L-ASNase. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)

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19 pages, 2194 KiB

Open AccessArticle

Metabolite Profiling and Antioxidant Activities in Seagrass Biomass

by Pilar Garcia-Jimenez, Milagros Rico, Diana del Rosario-Santana, Vicent Arbona, Marina Carrasco-Acosta and David Osca

Mar. Drugs 2025, 23(5), 193; https://doi.org/10.3390/md23050193 - 29 Apr 2025

Abstract

In this work, metabolite profiling of seeds and antioxidant analysis of fragments of two marine seagrasses, Posidonia oceanica and Cymodocea nodosa, were carried out to identify metabolite signature involved in seed viability and to evaluate the potential of fragments as a source of [...] Read more.

In this work, metabolite profiling of seeds and antioxidant analysis of fragments of two marine seagrasses, Posidonia oceanica and Cymodocea nodosa, were carried out to identify metabolite signature involved in seed viability and to evaluate the potential of fragments as a source of bioactive compounds. Using HILIC/QTOF-MS, UHPLC-MS and spectrophotometric analysis, seed metabolites and polyphenols and antioxidant activities, such as those of radical scavenging (RSA), reduction (FRAP, CUPRAC) and complexation (CCA), of rhizome fragments were evaluated. Metabolite comparison between seeds revealed differences across development stages (germinated and non-germinated) and seed types (dormant and non-dormant), providing insights into metabolic activity potentially associated with germination processes and seed viability. Furthermore, polyphenol analysis showed the highest content of caffeic acid in mature leaves (17.00 ± 0.02 μg g⁻¹ dw for P. oceanica and 98.00 ± 0.03 μg g⁻¹ dw for C. nodosa). Total phenolic content was correlated with flavonoids and with reduction and complexation activities. The combination of radical scavenging activity and t_1/2 was higher in P. oceanica than C. nodosa and also surpassed the commercial synthetic antioxidant BHA. We conclude P. oceanica and C. nodosa exhibit distinct seed metabolite profiles related to germination and type of seeds, and that fragments are rich in antioxidants, with potential as sustainable sources of bioactive compounds. Full article

(This article belongs to the Special Issue Marine Algae: Exploring Their Nutritional, Health, and Nutraceutical Potential)

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6 pages, 178 KiB

Open AccessEditorial

Marine Bioactive Peptides—Structure, Function, and Application 2.0

by Bin Wang and Chang-Feng Chi

Mar. Drugs 2025, 23(5), 192; https://doi.org/10.3390/md23050192 - 28 Apr 2025

Abstract

In recent years, people’s lifestyles have undergone relatively significant changes [...] Full article

(This article belongs to the Special Issue Marine Bioactive Peptides—Structure, Function, and Application 2.0)

14 pages, 853 KiB

Open AccessArticle

Improving the Value Utilization of Tuna Peptide Powder for the Cosmetics Field Through Ozone Oxidation

by Haolong Zheng, Shiyang Gu, Shiqi Huang, Yan Zhang, Feng Xu, Daofei Lv, Wenbing Yuan, Kongyu Zhu and Xin Chen

Mar. Drugs 2025, 23(5), 191; https://doi.org/10.3390/md23050191 - 28 Apr 2025

Abstract

The existing in vitro and clinical trial evidence supports the health and wellness benefits of collagen peptides sourced from various origins. Despite this, research on collagen peptides from tuna remains limited. Notably, tuna-derived peptides possess an inherent fishy odor, rendering them unsuitable for [...] Read more.

The existing in vitro and clinical trial evidence supports the health and wellness benefits of collagen peptides sourced from various origins. Despite this, research on collagen peptides from tuna remains limited. Notably, tuna-derived peptides possess an inherent fishy odor, rendering them unsuitable for direct application in humans. This study explores the enhancement of tuna peptides’ applicability in cosmetics through odor mitigation. We developed a dual-phase ozone treatment, employing both dry and wet ozone, to deodorize tuna peptide powder, enabling its use in cosmetic formulations. The deodorized tuna peptide powder can be used in cosmetics. We optimized the ozone nitrification and deodorization conditions for tuna peptide powder by adjusting the treatment time, ozone concentration, and temperature. Sensory evaluation and GC-MS analysis confirmed the effectiveness of fishy odor removal, offering a comprehensive understanding of the deodorization process. The findings reveal that wet ozonation at 50 °C with an ozone concentration of 99.1 mg/L for 40 min significantly reduces the fishy odor of tuna peptide powder. Notably, n-Hexaldehyde, the primary odor-contributing volatile compound, decreased by 66.5%, confirming the efficacy of ozone treatment in odor mitigation. Moreover, the protein activity within the powder remained unaffected, ensuring the preservation of its functional properties. This study demonstrates the efficacy of ozone oxidation in adapting tuna peptide powder for cosmetic use. Full article

(This article belongs to the Special Issue Marine Cosmeceuticals)

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31 pages, 2659 KiB

Open AccessReview

Recent Advancements in Marine Collagen: Exploring New Sources, Processing Approaches, and Nutritional Applications

by Joinul Islam and Kevin E. Mis Solval

Mar. Drugs 2025, 23(5), 190; https://doi.org/10.3390/md23050190 - 28 Apr 2025

Abstract

Collagen is a structural protein found in the connective tissues of terrestrial and marine animals. Its diverse functional attributes span its applications in several industries, including food, supplements, cosmetics, and pharmaceuticals. Typically derived from mammalian sources, collagen and its derivatives, including gelatin and [...] Read more.

Collagen is a structural protein found in the connective tissues of terrestrial and marine animals. Its diverse functional attributes span its applications in several industries, including food, supplements, cosmetics, and pharmaceuticals. Typically derived from mammalian sources, collagen and its derivatives, including gelatin and collagen peptides, are essential for the food and supplement industries. Recently, marine collagen has emerged as a viable mammalian collagen alternative due to its unique functionality and sustainability. Marine vertebrates and invertebrates are reliable sources of marine collagen. Some marine organisms are promising sustainable sources of collagen for nutritional applications. Recent research highlights significant advances in marine collagen extraction, processing, and novel applications. Hence, recent interest has propelled research in identifying novel collagen sources and advancing technologies to produce marine collagen-based products. Considering the recent scientific interest in marine collagen, this review provides an overview of recent progress in marine collagen production, including novel sources, innovative processing technologies, nutritional and functional properties, safety and quality control, current challenges, and future research directions. The review highlights certain challenges, including unpleasant odor, flavor, color, insufficient supply, and inconsistent quality of marine collagen. Future research should focus on increasing the collagen extraction yield, improving the smell and flavor, and developing novel delivery systems to increase bioavailability and functionality. Full article

(This article belongs to the Special Issue Marine Collagen: From Biological Insights to Biomedical Breakthroughs)

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24 pages, 6743 KiB

Open AccessArticle

Neuroprotective and Anti-Inflammatory Activity of Undaria pinnatifida Fucoidan In Vivo—A Proteomic Investigation

by Cheng Yang, Corinna Dwan, Barbara C. Wimmer, Maurizio Ronci, Richard Wilson, Luke Johnson and Vanni Caruso

Mar. Drugs 2025, 23(5), 189; https://doi.org/10.3390/md23050189 - 27 Apr 2025

Abstract

Undaria pinnatifida fucoidan (UPF), a bioactive sulphated polysaccharide, is widely recognised for its anti-inflammatory, antioxidant, antitumor, anticoagulant, antiviral, and immunomodulatory properties. However, the precise mechanisms by which UPF regulates inflammation and neuronal health remain unclear. This study aimed to investigate the effects of [...] Read more.

Undaria pinnatifida fucoidan (UPF), a bioactive sulphated polysaccharide, is widely recognised for its anti-inflammatory, antioxidant, antitumor, anticoagulant, antiviral, and immunomodulatory properties. However, the precise mechanisms by which UPF regulates inflammation and neuronal health remain unclear. This study aimed to investigate the effects of UPF supplementation on pro-inflammatory cytokines in skeletal muscle, small intestine, and the hypothalamus, as well as plasma cytokine levels. Additionally, a brain proteomic investigation in the nucleus accumbens (NAc) was performed to assess UPF’s impact on neuronal protein expression in mice. A total of 64 C57BL/6J mice were administered either a standard chow or high-fat diet (HFD) with or without UPF (400 mg/kg/day) for 10 weeks. In HFD-fed mice, UPF significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in skeletal muscle, small intestine, and hypothalamus, while also lowering circulating IL-1α and IL-6 levels. Proteomic analysis of the NAc revealed that UPF modulated proteins involved in oxidative stress, neuroinflammation, neurotransmitter regulation, and endoplasmic reticulum stress. In contrast, in chow-fed mice, UPF had no effect on the neuroinflammatory–oxidative stress markers but influenced the abundance of proteins associated with immune response and innate immunity. These findings suggest that UPF modulates stress-response pathways in a diet-dependent manner, supporting its potential neuroprotective role in inflammation-related disorders and brain health. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules, 2nd Edition)

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9 pages, 1438 KiB

Open AccessCommunication

Polyketides with a 6/6/6/6 Oxaphenalene Pyranone Skeleton from Marine-Derived Streptomyces sp. HDN150000

by Xiaoting Zhang, Falei Zhang, Wenxue Wang, Xingtao Ren, Tianjiao Zhu, Qian Che, Dehai Li and Guojian Zhang

Mar. Drugs 2025, 23(5), 188; https://doi.org/10.3390/md23050188 - 27 Apr 2025

Abstract

Three new structures named naphpyrone I–K (1–3) that contain a 6/6/6/6 oxaphenalene pyranone skeleton were isolated and purified from a marine-derived Streptomyces sp. HDN155000. Their chemical structures, including configurations, were elucidated by extensive NMR, MS, single-crystal X-ray diffraction, theoretical [...] Read more.

Three new structures named naphpyrone I–K (1–3) that contain a 6/6/6/6 oxaphenalene pyranone skeleton were isolated and purified from a marine-derived Streptomyces sp. HDN155000. Their chemical structures, including configurations, were elucidated by extensive NMR, MS, single-crystal X-ray diffraction, theoretical NMR calculations, DP4+ probability analysis, and ECD analyses. Naphpyrone K (3) showed cytotoxic activities against L-02, K562, NCI-H446/EP, MDA-MB-231, and NCI-H446 cancer cells with IC₅₀ values of 5.13, 3.34, 2.50, 2.61, and 2.20 μM, respectively. These findings highlight the potential for screening and developing therapeutic drugs from aromatic polyketides derived from marine actinobacteria. Full article

(This article belongs to the Special Issue Marine Streptomyces-Derived Natural Products 2024)

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14 pages, 1730 KiB

Open AccessArticle

Bioassay-Guided Procedure Coupled with HR-ESIMS Dereplication for Isolation of Antiproliferative Bromo-Tyramine Derivative from Aplysina cauliformis

by Germana Esposito, Maria Ponticelli, Luigi Milella, Ludovica Lela, Roberta Teta, Joseph R. Pawlik, Daniela Russo and Valeria Costantino

Mar. Drugs 2025, 23(5), 187; https://doi.org/10.3390/md23050187 - 27 Apr 2025

Abstract

The marine environment is vital for sustaining life on Earth and offers a significant, untapped source of bioresources that could enhance the blue economy. The present investigation used our protocol to quickly identify bioactive molecules in Aplysina cauliformis organic extracts. This procedure combines [...] Read more.

The marine environment is vital for sustaining life on Earth and offers a significant, untapped source of bioresources that could enhance the blue economy. The present investigation used our protocol to quickly identify bioactive molecules in Aplysina cauliformis organic extracts. This procedure combines a bioassay-guided approach with the dereplication of mass data through bioinformatic analysis. This approach identified the compound N,N,N-trimethyl-3,5-dibromotyramine, a bromo-tyramine analog that showed promising antiproliferative activity on HepG2 cell lines, with an IC₅₀ value of 37.49 ± 1.94 μg/mL after 24 h. Furthermore, the evaluation of related gene expression confirmed the mechanism of cell death to be apoptosis. N,N,N-trimethyl-3,5-dibromotyramine increased the expression of pro-apoptotic β-cell lymphoma 2-associated X protein (BAX) and Poly (ADP-ribose) polymerase (PARP-1) cleavage (c-PARP-1) and downregulated the anti-apoptotic β-cell lymphoma 2 (BCL-2) and phospho-Akt (p-AKT). This report presents N,N,N-trimethyl-3,5-dibromotyramine from Aplysina cauliformis and its antiproliferative activity against the HepG2 cell line. Full article

(This article belongs to the Special Issue Marine Natural Products and Signaling Pathways, 2nd Edition)

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12 pages, 1539 KiB

Open AccessArticle

Purpuramine R, a New Bromotyrosine Isolated from Pseudoceratina cf. verrucosa Collected in the Kingdom of Tonga

by Jennie L. Ramirez-Garcia, Hannah Lee-Harwood, David Ackerley, Michelle Kelly, S. Vailala Matoto, Patricia Hunt, A. Jonathan Singh and Robert A. Keyzers

Mar. Drugs 2025, 23(5), 186; https://doi.org/10.3390/md23050186 - 27 Apr 2025

Abstract

Sponges in the verongiid genus Pseudoceratina Carter are well-known producers of bioactive secondary metabolites. Chemical screening of a Tongan P. cf. verrucosa Bergquist using NMR highlighted the presence of aromatic natural products. Subsequent extraction and purification of P. cf. verrucosa yielded a new [...] Read more.

Sponges in the verongiid genus Pseudoceratina Carter are well-known producers of bioactive secondary metabolites. Chemical screening of a Tongan P. cf. verrucosa Bergquist using NMR highlighted the presence of aromatic natural products. Subsequent extraction and purification of P. cf. verrucosa yielded a new bromotyrosine, purpuramine R (1), that exhibits moderate (MIC 16 µg/mL) antibacterial activity against Gram-positive Staphylococcus aureus. The E-geometry of the oxime was confirmed using a combination of NMR and computational approaches. Additionally, computational conformational analysis indicates that purpuramine R adopts a hairpin orientation, stabilized by intramolecular hydrogen and halogen bonds. Knowledge of this stabilized conformation can inform synthetic approaches to make analogues of the purpuramines for future SAR studies. Full article

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

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18 pages, 1637 KiB

Open AccessArticle

Characterization of the VOC Promoter That Is Active Under Low-Salinity Conditions in the Diatom Phaeodactylum tricornutum

by Charlotte Toustou, Carole Plasson, Marie-Christine Kiefer-Meyer and Muriel Bardor

Mar. Drugs 2025, 23(5), 185; https://doi.org/10.3390/md23050185 - 26 Apr 2025

Abstract

Microalgae such as Phaeodactylum tricornutum are promising cell biofactories for the production of high-value molecules, including monoclonal antibodies (mAbs). However, to date, the production of mAbs in P. tricornutum using the inducible nitrate reductase (NR) promoter has yielded only a limited amount of [...] Read more.

Microalgae such as Phaeodactylum tricornutum are promising cell biofactories for the production of high-value molecules, including monoclonal antibodies (mAbs). However, to date, the production of mAbs in P. tricornutum using the inducible nitrate reductase (NR) promoter has yielded only a limited amount of mAbs. Therefore, the identification of a robust promoter that produces high yields of mAbs is crucial for the development of a cost-effective expression system. To date, only a few endogenous promoters have been characterized in P. tricornutum. In this study, we identified thirty-three potential “strong” endogenous promoters based on our previously published transcriptomic data from the P. tricornutum Pt3 strain. These putative promoter sequences were cloned into an episomal vector and fused to the gene encoding enhanced green fluorescent protein (eGFP). Their strength was assessed by measuring eGFP fluorescence, which reflects the level of eGFP protein expression. Of the thirty-three promoters, thirteen were able to successfully drive eGFP protein expression. Among them, the best results were obtained with the VOC promoter, which allowed a significant increase in eGFP expression compared to that induced by the NR promoter. These results contribute to the identification of new genetic tools that can be used in future studies to increase the yield of production of recombinant proteins in P. tricornutum at an industrial scale. Full article

(This article belongs to the Special Issue Applications of Marine Microalgal Biotechnology)

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19 pages, 1093 KiB

Open AccessReview

Harnessing Artificial Intelligence to Revolutionize Microalgae Biotechnology: Unlocking Sustainable Solutions for High-Value Compounds and Carbon Neutrality

by Yijian Wu, Lei Shan, Weixuan Zhao and Xue Lu

Mar. Drugs 2025, 23(5), 184; https://doi.org/10.3390/md23050184 - 25 Apr 2025

Abstract

Microalgae offer significant potential in diverse fields, including biofuels, carbon capture, and high-value bioproducts. However, optimizing and scaling microalgae cultivation systems present several challenges due to the dynamic interactions among environmental factors such as light intensity, temperature, pH, nutrient concentration, and CO₂ [...] Read more.

Microalgae offer significant potential in diverse fields, including biofuels, carbon capture, and high-value bioproducts. However, optimizing and scaling microalgae cultivation systems present several challenges due to the dynamic interactions among environmental factors such as light intensity, temperature, pH, nutrient concentration, and CO₂ levels, as well as species-specific biological variability. Recent advancements in artificial intelligence (AI), particularly machine learning (ML) and automation, have provided innovative solutions to these challenges. This review explored the role of AI in enhancing microalgae technology, focusing on optimizing cultivation conditions, improving CO₂ capture, maximizing biomass production, and automating system processes. Key case studies highlight successful applications of AI in biofuel production, carbon capture projects, and high-value compound manufacturing. Key case studies demonstrate that AI-driven models can increase biomass productivity by up to 15–57%, improve CO₂ biofixation efficiency, and enhance lipid and high-value compound yields by more than 20–43% compared to traditional methods. Additionally, we discussed the limitations of current AI models, particularly in data availability and species-specific variability, and suggested future research directions to enhance the integration of AI and microalgae systems. By leveraging AI’s potential, microalgae technologies can become more efficient, scalable, and economically viable, addressing global sustainability challenges such as energy production and climate change mitigation. Full article

(This article belongs to the Special Issue Metabolic Engineering Strategy for Producing High-Value Products in Microalgae)

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25 pages, 9043 KiB

Open AccessArticle

High Affinity Aptamers and Their Specificity for Azaspiracid-2 Using Capture-SELEX

by Jiaping Yang, Xinhao Li, Weiqin Sun, Yunyi Cui, Han Chen, Yao Yang, Mingjuan Sun and Lianghua Wang

Mar. Drugs 2025, 23(5), 183; https://doi.org/10.3390/md23050183 - 25 Apr 2025

Abstract

Azaspiracids are a type of polyether toxin. Currently, the existing detection methods for azaspiracids all have certain drawbacks. Aptamers offer a cost-effective and convenient approach for the detection of azaspiracids. By employing the Capture-SELEX (Systematic evolution of ligands by exponential enrichment) method to [...] Read more.

Azaspiracids are a type of polyether toxin. Currently, the existing detection methods for azaspiracids all have certain drawbacks. Aptamers offer a cost-effective and convenient approach for the detection of azaspiracids. By employing the Capture-SELEX (Systematic evolution of ligands by exponential enrichment) method to screen aptamers specific to azaspiracid-2, a high-affinity aptamer can be identified for toxin detection. The bin ding affinity of the toxin is verified using biolayer interferometry (BLI) technology. Additionally, computer simulations are utilized to explore the binding sites of the aptamer and conduct molecular dynamics simulations to investigate the stability of the aptamer–toxin complex. Further optimization of the obtained aptamers is carried out to enhance their affinity for the toxin. Ultimately, two aptamers, JD2-RM3-27C28T and JD3-RMM1, are obtained, with dissociation constants (K_D) improved by two orders of magnitude (K_D = 8.7 × 10⁻⁸ nM and K_D = 6.8 × 10⁻⁸ nM, respectively). These aptamers have the advantage of being incorporated into a new AZA2 assay that is more accurate and ethical than biological monitoring methods, and more economical than LC-MS. In the future, this is expected to demonstrate significant advantages in the fields of food safety, environmental toxin monitoring, toxin exposure diagnosis, and public health monitoring. Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section "Marine Toxins")

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21 pages, 2672 KiB

Open AccessArticle

A Comparative Study of the Fatty Acid Profile of Non-Edible and Edible Tissues of Raw and Processed Common Octopus (Octopus vulgaris)

by Luis Freiría-Martínez, Marcos Trigo, Ricardo Prego and Santiago P. Aubourg

Mar. Drugs 2025, 23(5), 182; https://doi.org/10.3390/md23050182 - 24 Apr 2025

Abstract

A comparative study of the fatty acid (FA) composition of non-edible (viscera) and edible (mantle and arm) tissues of octopus (Octopus vulgaris) was carried out. According to the specimen size, three different groups (1–2 kg, 2–3 kg, and 3–4 kg, respectively) [...] Read more.

A comparative study of the fatty acid (FA) composition of non-edible (viscera) and edible (mantle and arm) tissues of octopus (Octopus vulgaris) was carried out. According to the specimen size, three different groups (1–2 kg, 2–3 kg, and 3–4 kg, respectively) were taken into account. The effect of the cooking process (40 min at 90 °C) and frozen storage (4 months at −18 °C) was analyzed. In all kinds of samples, the polyunsaturated FA (PUFA) group was the most abundant (p < 0.05) and monounsaturated FAs were the least abundant (p < 0.05). Lower (p < 0.05) ω3-PUFA, ω3/ω6 ratio and docosahexaenoic acid values were detected in viscera (35.4–41.9%, 3.0–4.5%, and 12.7–17.5%, respectively) than in edible tissues (44.4–52.5%, 4.1–6.1%, and 24.3–30.1%, respectively). Conversely, higher (p < 0.05) eicosapentaenoic acid content was detected in viscera (19.6–21.9%) than in the edible tissues (17.2–19.3%). In most cases, the cooking process and frozen storage led to an average decrease in the PUFA and ω3-PUFA content and to an increase in the saturated FA presence. In agreement with current nutritional recommendations, all tissues showed great levels of highly valuable indices regarding the lipid fraction. The study proves that viscera, a waste substrate, can be considered a relevant source for food and pharmaceutical industrial requirements. Full article

(This article belongs to the Special Issue Fatty Acids from Marine Organisms, 2nd Edition)

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18 pages, 3138 KiB

Open AccessArticle

Aspergillusidone G Exerts Anti-Neuroinflammatory Effects via Inhibiting MMP9 Through Integrated Bioinformatics and Experimental Analysis: Implications for Parkinson’s Disease Intervention

by Fangfang Ban, Longjian Zhou, Zhiyou Yang, Yayue Liu and Yi Zhang

Mar. Drugs 2025, 23(5), 181; https://doi.org/10.3390/md23050181 - 23 Apr 2025

Abstract

Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from Aspergillus unguis DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP⁺)-induced primary [...] Read more.

Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from Aspergillus unguis DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP⁺)-induced primary cortical neurons and anti-neuroinflammatory property, promising to be a potential therapeutic agent for Parkinson’s disease (PD). To further explore the anti-PD potential and mechanisms of Asp G, we employed network pharmacology, cellular experiments, and various biological techniques for analysis and validation. The analysis of network pharmacology suggested that Asp G’s anti-PD potential might be attributed to its modulation of inflammation. The data from nitric oxide (NO) detection, qRT-PCR, and Western blot confirmed that Asp G dose-dependently inhibited lipopolysaccharide (LPS)-stimulated NO production, with 40 μM Asp G suppressing 90.54% of the NO burst compared to the LPS group, and suppressed the overproduction of inflammatory-related factors in LPS-induced BV2 cells. Further protein–protein interaction analysis indicated that matrix metalloproteinase 9 (MMP9), a promising target for PD intervention, was the most likely anti-PD target of Asp G, and the results of gelatin zymography, qRT-PCR, and Western blot validated that Asp G could inhibit the active and inactive forms of MMP9 directly and indirectly, respectively. Notably, the inhibition of 67 kDa-MMP9 by Asp G is expected to compensate for the inability of TIMP-1 to inhibit this form. Furthermore, a selective inhibitor of MMP9 (20 μM SB-3CT) further potentiated the anti-inflammatory effects of Asp G (20 μM), with inhibition rate on NO increasing from 27.57% to 63.50% compared to LPS group. In summary, our study revealed that Asp G exerts anti-neuroinflammatory effects by inhibiting MMP9, which provides a valuable lead compound for the development of anti-neuroinflammatory drugs and offers insights into the intervention of PD-associated neuroinflammation. Future studies will further investigate the upstream regulatory mechanisms of Asp G-mediated MMP9 inhibition and its effects in in vivo PD models. Full article

(This article belongs to the Special Issue Chemoinformatics for Marine Drug Discovery)

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14 pages, 6186 KiB

Open AccessArticle

Low-Molecular-Weight Fucoidan Inhibits Thromboinflammation and Ameliorates Deep Vein Thrombosis via Targeting S100A8/A9

by Yiting Feng, Weiqing Zhao, Siwen Fang, Jingwen Zhao, Wanshuai Wang, Shaoyun Zhou, Tianyu Wang, Xinke Fang, Xue Chen, Muhammad Awais, Chao Cai, Chuanbin Shen and Ming Liu

Mar. Drugs 2025, 23(5), 180; https://doi.org/10.3390/md23050180 - 22 Apr 2025

Abstract

Deep vein thrombosis (DVT) is a prevalent life-threatening complication among hospitalized patients. DVT is characterized by the hypercoagulability and thromboinflammation in which platelet activation and neutrophil extracellular trap (NET) formation are critically involved. Studies have shown that S100A8/A9 is significantly elevated in patients [...] Read more.

Deep vein thrombosis (DVT) is a prevalent life-threatening complication among hospitalized patients. DVT is characterized by the hypercoagulability and thromboinflammation in which platelet activation and neutrophil extracellular trap (NET) formation are critically involved. Studies have shown that S100A8/A9 is significantly elevated in patients with DVT, and is closely associated with platelet activation and NET formation. Fucoidan, the marine polysaccharide derived from Fucus algae, has potential anti-inflammatory and cardioprotective effects. We found low-molecular-weight fucoidan (LMF) bound to S100A8/A9 with an equilibrium dissociation constant (KD) of 2.368 × 10⁻⁸ M. LMF inhibited S100A8/A9-induced platelet hyperactivity and NET formation in vitro, and ameliorated DVT without significantly perturbing hemostasis in vivo. Our results indicate that the alarmin protein S100A8/A9 is a novel target of LMF. LMF may have therapeutic potential in S100A8/A9-induced thromboinflammation in DVT. Full article

(This article belongs to the Special Issue Celebrating the 100th Anniversary of Ocean University of China: Potential Therapeutic Benefits of Marine Novel Natural Products)

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15 pages, 2375 KiB

Open AccessArticle

Synthesis and Evaluation of Antitumor and Anti-Angiogenesis Activity of Pyrone- or Pyridone-Embedded Analogs of Cortistatin A

by Yuri Fujimoto, Kanako Mizuno, Yuta Nakamura, Masayoshi Arai and Naoyuki Kotoku

Mar. Drugs 2025, 23(4), 179; https://doi.org/10.3390/md23040179 - 20 Apr 2025

Abstract

Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed and synthesized. [...] Read more.

Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed and synthesized. Among the prepared analogs, the pyridone analog 19 bearing a methyl group at C-2 and a hydroxyl group at C-4 showed potent and selective growth inhibitory activity against human umbilical vein endothelial cells (HUVECs, IC₅₀ = 0.001 µM, selective index over that against human epidermoid carcinoma KB3-1 cells = 6400), exceeding those of natural products. The analog 19 of oral administration exhibited excellent in vivo antitumor activity in mice subcutaneously inoculated with sarcoma S180 cells. Full article

(This article belongs to the Special Issue Synthetic Studies of Marine Bioactive Natural Products and Analogs to Develop Novel Drug Leads)

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18 pages, 8998 KiB

Open AccessArticle

Synthesis and Evaluation of Aquatic Antimicrobial Peptides Derived from Marine Metagenomes Using a High-Throughput Screening Approach

by Kaiyue Wu, Guangxin Xu, Yin Tian, Guizhen Li, Zhiwei Yi and Xixiang Tang

Mar. Drugs 2025, 23(4), 178; https://doi.org/10.3390/md23040178 - 20 Apr 2025

Abstract

Bacterial diseases cause high mortality and considerable losses in aquaculture. The rapid expansion of intensive aquaculture has further increased the risk of large-scale outbreaks. However, the emergence of drug-resistant bacteria, food safety concerns, and environmental regulations have severely limited the availability of antimicrobial. [...] Read more.

Bacterial diseases cause high mortality and considerable losses in aquaculture. The rapid expansion of intensive aquaculture has further increased the risk of large-scale outbreaks. However, the emergence of drug-resistant bacteria, food safety concerns, and environmental regulations have severely limited the availability of antimicrobial. Compared to traditional antibiotics, antimicrobial peptides (AMPs) offer broad spectrum activity, physicochemical stability, and lower resistance development. However, their low natural yield and high extraction costs along with the time-consuming and expensive nature of traditional drug discovery, pose a challenge. In this study, we applied a machine-learning macro-model to predict AMPs from three macrogenomes in the water column of South American white shrimp aquaculture ponds. The AMP content per megabase in the traditional earthen pond (TC1) was 1.8 times higher than in the biofloc pond (ZA1) and 63% higher than in the elevated pond (ZP11). A total of 1033 potential AMPs were predicted, including 6 anionic linear peptides, 616 cationic linear peptides, and 411 cationic cysteine-containing peptides. After screening based on structural, and physio-chemical properties, we selected 10 candidate peptides. Using a rapid high-throughput cell-free protein expression system, we identified nine peptides with antimicrobial activity against aquatic pathogens. Three were further validated through chemical synthesis. The three antimicrobial peptides (K-5, K-58, K-61) showed some inhibitory effects on all four pathogenic bacteria. The MIC of K-5 against Vibrio alginolyticus was 25 μM, the cell viability of the three peptides was higher than 70% at low concentrations (≤12.5 μM), and the hemolysis rate of K-5 and K-58 was lower than 5% at 200 μM. This study highlights the benefits of machine learning in AMP discovery, demonstrates the potential of cell-free protein synthesis systems for peptide screening, and provides an efficient method for high-throughput AMP identification for aquatic applications. Full article

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18 pages, 3560 KiB

Open AccessArticle

Exploring the In Vivo Fate of β-1, 3/1, 6-Glucan Using Quantitative Tandem Mass Spectrometry Based on a Structure-Specific Fragment

by Shuying Xu, Jiale Hao, Chunyan Ye, Xintong Li, Pengcheng Gao, Ni Song, Chanjuan Liu, Youjing Lv, Guangli Yu and Guoyun Li

Mar. Drugs 2025, 23(4), 177; https://doi.org/10.3390/md23040177 - 20 Apr 2025

Abstract

β-glucan, a promising drug candidate for immuno-antitumor therapy, holds tremendous potential for clinical applications. However, the absence of highly sensitive quantitative methods for polysaccharides, attributed to their complicated chemical structures and susceptibility to endogenous interference, has posed significant challenges for their clinical development. [...] Read more.

β-glucan, a promising drug candidate for immuno-antitumor therapy, holds tremendous potential for clinical applications. However, the absence of highly sensitive quantitative methods for polysaccharides, attributed to their complicated chemical structures and susceptibility to endogenous interference, has posed significant challenges for their clinical development. Here, we report a highly sensitive and reliable analytical strategy for quantifying β-1, 3/1, 6-glucan derived from Durvillaea antarctica (BG136) in various biological matrices. This approach integrates targeted depolymerization and derivatization, followed by oligosaccharide isomer fingerprinting using ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). The absolute quantification of BG136 relied on the abundance of the structure-specific trisaccharide (Glc-β1, 6-Glc-β1, 3-Glc) generated. This methodology not only facilitates prototype-based BG136 administration but also exhibits remarkable sensitivity. Following method optimization and validation, we successfully explored the in vivo fate of BG136 across multiple models, including cellular uptake and release kinetics, as well as preclinical and clinical pharmacokinetics. These achievements provide insight into the “black box” of BG136 from administration to elimination in vivo. This work marks the first practical application of this strategy in complex biological matrices, offering methodological support for the successful execution of the BG136 Phase I clinical trial. Full article

(This article belongs to the Special Issue Marine Polysaccharides and Oligosaccharides: Extraction and Biological Activities)

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