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Mar. Drugs, Volume 23, Issue 9 (September 2025) – 37 articles

Cover Story (view full-size image): Glycolipids are an important class of marine natural products with potential for sustainable bioproduct manufacturing. Their amphiphilicity and structure-dependent bioactivities underpin applications in nutraceuticals, pharmaceuticals, and cosmetics. Yet their discovery and development remain limited due to the laboriousness of extraction and characterisation from complex biomasses. This review summarises advanced analytical approaches tailored to different glycolipid subclasses, covering methods of extraction/enrichment and TLC-based rapid detection, alongside LC–MS/MS methodologies for high-throughput structural characterisation. These methods enable rapid profiling of bioactive and functional glycolipid structures to support bioproduct development from a diverse range of marine biomasses including seaweeds, fish, and shellfish. View this paper
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19 pages, 2545 KB  
Article
Synthesis and Biological Evaluation of Marine-Inspired Benzothiazole Derivatives as Retinoid X Receptor-α Antagonists with Anti-Cancer Activities
by Yingting Lin, Ming Peng, Renjing Yang, Guanghui Wang, Junjie Chen, Rong Ding, Cuiling Sun, Wenjing Tian and Haifeng Chen
Mar. Drugs 2025, 23(9), 368; https://doi.org/10.3390/md23090368 - 21 Sep 2025
Viewed by 224
Abstract
Retinoid X receptor α (RXRα) plays a vital role in multiple biological and pathological processes and represents a promising therapeutic target for anti-tumor drug design. Inspired by the marine-derived RXRα antagonist meroterpenthiazole A, 21 undescribed benzothiazole derivatives were designed and synthesized. The inhibitory [...] Read more.
Retinoid X receptor α (RXRα) plays a vital role in multiple biological and pathological processes and represents a promising therapeutic target for anti-tumor drug design. Inspired by the marine-derived RXRα antagonist meroterpenthiazole A, 21 undescribed benzothiazole derivatives were designed and synthesized. The inhibitory effects of 21 derivatives on RXRα transactivation and their anti-tumor activities against MDA-MB-231 cells were evaluated. Compounds 4a4h, 6a6b, 7c7f, and 7h7i inhibited 9-cis-retinoic acid-induced RXRα transactivation, while compounds 3b, 4f4h, 7a, 7c, 7f, and 7h7i exhibited inhibitory effects on the proliferation of MDA-MB-231 cells. Meanwhile, the structure–activity relationships governing both the RXRα antagonist effects and the anti-proliferative activities against MDA-MB-231 cells were discussed. Compound 7i exhibited the most potent inhibitory effects on the proliferation of MDA-MB-231 cells with an IC50 value of 16.5 μM. Further mechanism studies revealed that compound 7i induced G2/M phase arrest in MDA-MB-231 cells, accompanied by dose-dependent downregulation of Cyclin B1 and CDK1 protein expression. However, these effects were abolished in RXRα-knockout MDA-MB-231 cells, indicating that the anti-proliferative and cell cycle arrest activities of 7i were RXRα-dependent. Cellular Thermal Shift Assay (CETSA) and molecular docking studies further confirmed that 7i directly bound to RXRα, thereby mediating its anti-cancer efficacy. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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27 pages, 2810 KB  
Article
Meat Nutritional Value and Exoskeleton Valorisation of Callinectes sapidus from Three Sites of Biological and Ecological Interest in Morocco: Scientific Insights Toward a Management Strategy in the Mediterranean Sea
by Kamal Gourari, Youness Mabrouki, Abdelkhaleq Fouzi Taybi, Abdessadek Essadek, Valentina Tanduo, Fabio Crocetta, Ilyesse Rahhou, Chaouki Belbachir, Lucia Rizzo and Bouchra Legssyer
Mar. Drugs 2025, 23(9), 367; https://doi.org/10.3390/md23090367 - 21 Sep 2025
Viewed by 327
Abstract
Biological invasions threaten biodiversity worldwide. The American blue crab Callinectes sapidus Rathbun, 1896, among the Mediterranean’s most damaging invaders, takes up the challenge to transform this threat into gain. To turn its impact into economic value and guide control efforts, we analysed separately [...] Read more.
Biological invasions threaten biodiversity worldwide. The American blue crab Callinectes sapidus Rathbun, 1896, among the Mediterranean’s most damaging invaders, takes up the challenge to transform this threat into gain. To turn its impact into economic value and guide control efforts, we analysed separately the meat composition and exoskeleton biopolymers of adult crabs from three Moroccan protected Sites of Biological and Ecological Interest: Marchica Lagoon (S1), Moulouya Estuary (S2), and Al Hoceima National Park (S3). Marchica specimens exhibited the highest protein content (21.87 ± 1.15 g 100 g−1, p < 0.001) and an elevated lipid fraction, yielding nutrient-dense meat suitable for premium markets. Moulouya crabs were noted for their taste potential, with a higher concentration of fat (1.73 ± 0.09%) and carbohydrates (0.91 ± 0.1%). Al Hoceima individuals displayed markedly mineralised exoskeletons producing lean and low-fat meat, valued in dietary applications. Exoskeleton organic-to-mineral (OM/MM) ratios and proximate composition revealed three adaptive profiles, opportunistic (S1), acclimatory (S2), and conservative (S3), presumably correlated to local salinity, productivity, and substrate conditions, underscoring the species’ phenotypic plasticity. X-ray diffraction confirmed the α-chitin polymorph, while FTIR analysis indicated degrees of deacetylation consistent with high-purity chitosan. These findings support the development of a site-specific circular economy framework and may contribute to the ecological resilience of Morocco’s protected coastal areas. Full article
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63 pages, 828 KB  
Review
Extraction of Marine Bioactive Compounds from Seaweed: Coupling Environmental Concerns and High Yields
by Carlos Cardoso, Joana Matos and Cláudia Afonso
Mar. Drugs 2025, 23(9), 366; https://doi.org/10.3390/md23090366 - 19 Sep 2025
Viewed by 561
Abstract
This review examines recent advances in the extraction of valuable compounds from seaweed biomass, focusing on practical feasibility and environmental sustainability. There is a growing importance of seaweed biomass in terms of the study and acknowledgment of its untapped biotechnological potential (multiple compounds [...] Read more.
This review examines recent advances in the extraction of valuable compounds from seaweed biomass, focusing on practical feasibility and environmental sustainability. There is a growing importance of seaweed biomass in terms of the study and acknowledgment of its untapped biotechnological potential (multiple compounds and biological activities) and in terms of economic impact. Conventional extraction techniques largely fail to address this challenge, even if optimized. This has led to the development and testing of innovative technologies as solutions for a ‘green’ and effective extraction of components from seaweed biomass and to biorefinery processes. There are large differences in outcomes between alternative processes, depending on the matrix, operational parameters, and targeted compounds and activities. Despite the positive results of some techniques, such as those based on physical mechanisms, namely Microwave-Assisted Extraction (MAE) and Ultrasound-Assisted Extraction (UAE), and on enzymatic selectivity, i.e., Enzyme-Assisted Extraction (EAE), there is no universally effective technique and approach, thus justifying integrated approaches combining different techniques. The application of ‘green’ solvents was also assessed and proven to harbor a large potential, just as the wet route. Although technical difficulties, outcome variability, and economic viability problems are relevant, recent progress in seaweed processing paves the way for a future blue economy. Full article
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18 pages, 3997 KB  
Article
Novel pH-Responsive PSS-Loaded Chitosan Matrix Nanoparticles Ameliorate Pressure Overload-Induced Cardiac Hypertrophy
by Meijie Xu, Zhen Fan, Dingfu Wang, Dan Li, Haimiao Zou, Yiting Xue, Shixin Wang and Chunxia Li
Mar. Drugs 2025, 23(9), 365; https://doi.org/10.3390/md23090365 - 19 Sep 2025
Viewed by 208
Abstract
Cardiac hypertrophy is a critical contributor to cardiac dysfunction and the development of heart failure, yet effective therapeutic strategies remain limited. Propylene glycol alginate sulfate sodium (PSS) is a marine sulfated polysaccharide drug used in the treatment of cardiovascular diseases and has shown [...] Read more.
Cardiac hypertrophy is a critical contributor to cardiac dysfunction and the development of heart failure, yet effective therapeutic strategies remain limited. Propylene glycol alginate sulfate sodium (PSS) is a marine sulfated polysaccharide drug used in the treatment of cardiovascular diseases and has shown cardiac function benefits. Here, we designed a pH-responsive PSS-loaded nanoparticle drug delivery system. It was self-assembled by negatively charged PSS with positively charged trimethyl chitosan glycocholic acid (TMC-GA) via electrostatic interaction, and further stabilized the nanoparticles with Hydroxypropyl methylcellulose phthalate (HP55) excipients. The prepared TMC-GA/HP55@PSS nanoparticles were spherical, with a mean particle size of 361.5 ± 1.26 nm, zeta potential of −30.3 ± 0.9 mV, and encapsulation efficiency of 92.52 ± 2.4%. In vitro release study demonstrated the pH-responsive property of TMC-GA/HP55@PSS under intestinal conditions and facilitated nanoparticles absorption in the intestinal epithelium. In vitro experiments confirmed the biocompatibility of PSS and its ability to improve myocardial cell hypertrophy. In vivo, both PSS and its nanoparticles significantly ameliorated pressure overload–induced cardiac hypertrophy in mice, with TMC-GA/HP55@PSS exhibiting better cardioprotective efficacy. This study is the first to integrate pH-responsiveness and bile acid transport-mediated uptake into PSS nanocarrier systems. The findings provide valuable data and enlightenment for designing novel formulations and expanding the clinical applications of PSS. Full article
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20 pages, 2967 KB  
Article
Effect of Precipitated Extracellular Marennine on Angiogenesis and Tumour Cell Proliferation
by Mostefa Fodil, Javier Muñoz-Garcia, Amel-Khitem Benali, Jasmina Rogozarski, Virginie Mignon, Honora Labrana, Anna Lokajczyk, Pamela Pasetto, Jean-Luc Mouget, Catherine Boisson-Vidal and Dominique Heymann
Mar. Drugs 2025, 23(9), 364; https://doi.org/10.3390/md23090364 - 19 Sep 2025
Viewed by 269
Abstract
Angiogenesis is a fundamental biological process involved in the formation of new blood vessels from the pre-existing vascular network. In addition to physiological processes, angiogenesis is also implicated in pathological conditions such as tumour growth and metastatic progression. Research on marennine, a water-soluble [...] Read more.
Angiogenesis is a fundamental biological process involved in the formation of new blood vessels from the pre-existing vascular network. In addition to physiological processes, angiogenesis is also implicated in pathological conditions such as tumour growth and metastatic progression. Research on marennine, a water-soluble blue-green pigment produced by the marine diatom Haslea ostrearia, has highlighted various promising biological activities. In vivo studies have suggested the potential of marennine in cancer treatment. However, these studies were conducted with crude extracts, the exact composition of which remained poorly defined. In this context, our study aimed to explore the effects of marennine on angiogenesis and tumour proliferation by using a Precipitated Extracellular Marennine (PEMn) extract. Our results confirmed the antiproliferative properties of PEMn on several cancer cell lines associated with angiogenic tumours. We then analysed its impact on the key steps of the angiogenic process, including Endothelial Colony-Forming Cells (ECFCs) proliferation, migration, and tubulogenesis. In parallel, we investigated the underlying mechanisms of its action, notably by assessing its effects on cell cycle regulation, senescence, and apoptosis. PEMn significantly inhibited tumour cell proliferation, induced ECFC senescence and apoptosis, impaired migration and tubulogenesis, and downregulated VEGFR-1 expression, highlighting its potential as a novel marine-derived antiangiogenic compound. These findings provide deeper insights into the mechanisms of action of marennine, identifying this bioactive natural compound as a novel bioactive compound in cancer treatment. Full article
(This article belongs to the Collection Bioactive Compounds from Marine Plankton)
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23 pages, 4097 KB  
Review
Amyloid-like Structures in Marine Adhesive Proteins
by Mariana Rodrigues Santos, Bárbara Joana Henriques and Romana Santos
Mar. Drugs 2025, 23(9), 363; https://doi.org/10.3390/md23090363 - 19 Sep 2025
Viewed by 417
Abstract
The formation of amyloid-like structures is commonly linked to neurodegenerative diseases, such as Parkinson’s and Alzheimer’s. However, proteins can form amyloid-like structures in non-pathological contexts, referred to as functional amyloids. We review the current knowledge on the evolutionary and ecological significance of the [...] Read more.
The formation of amyloid-like structures is commonly linked to neurodegenerative diseases, such as Parkinson’s and Alzheimer’s. However, proteins can form amyloid-like structures in non-pathological contexts, referred to as functional amyloids. We review the current knowledge on the evolutionary and ecological significance of the presence of proteins presenting amyloid-like structures in adhesive secretions (both permanent and non-permanent) produced by several marine organisms; in addition, we analyze the molecular and structural properties that make them well suited for this task and their possible biomimetic and industrial applications. Full article
(This article belongs to the Special Issue Marine Biomaterials: Insights from Marine Invertebrates)
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23 pages, 2053 KB  
Article
Integrated Omics-Based Discovery of Bioactive Halogenated Metabolites from the Deep-Sea Streptomyces sp. B188M101
by Emmanuel Tope Oluwabusola, Stephen A. Jackson, Cristina Brunati, Stefanie Gackstatter, Hannah Vedder, Marianna Iorio, Gargee Chawande, Lekha Menon Margassery, Giang-Son Nguyen, David J. Clarke, Rainer Ebel, Marcel Jaspars and Alan D. W. Dobson
Mar. Drugs 2025, 23(9), 362; https://doi.org/10.3390/md23090362 - 19 Sep 2025
Viewed by 509
Abstract
Using the one-strain-many-compounds (OSMAC) culturing approach, metabolomic studies, and bioassay-guided purification, we have isolated and characterised three new chlorinated natural products, agelolines B-D (13), together with two known compounds, ageloline A (4) and gausemycin A (5 [...] Read more.
Using the one-strain-many-compounds (OSMAC) culturing approach, metabolomic studies, and bioassay-guided purification, we have isolated and characterised three new chlorinated natural products, agelolines B-D (13), together with two known compounds, ageloline A (4) and gausemycin A (5), which have been identified by high-resolution mass spectrometry and 1D and 2D NMR analyses. The preliminary evaluation of three small-scale extracts (M400, R358 and SGG) against the fish pathogen, Aeromonas salmonicida subsp. achromogenes KELDUR265-87, showed that the R358 extract displayed significant activity. Furthermore, the natural products (15) were evaluated against the fish pathogen Aeromonas salmonicida and human pathogens (Stenotrophomonas maltophilia L2125, Staphylococcus aureus ATCC6538P, and S. pneumoniae L44) using a serial dilution assay. Compound 3 displayed activity against Staphylococcus aureus ATCC6538P, S. maltophilia L2125, and S. pneumoniae L44 with MIC values of 6, 32, and 64 µg/mL, respectively. Interestingly, only gausemycin A (5) exhibited considerable inhibition against A. salmonicida with an MIC value of 32 µg/mL, and the activity increased by two-fold when supplemented with 0.45 mM calcium salt, while 2 and 4 showed moderate inhibition against S. maltophilia L2125. The biosynthetic pathways of compounds 14 were proposed. This is the first report of specific inhibition of A. salmonicida by 5. Full article
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13 pages, 1846 KB  
Article
Enhancing Phycoerythrin Production of Marine Red Microalga Porphyridium purpureum with Low Salinity and Semi-Continuous Culture Strategy
by Chulin Li, Houbo Wu, Hualian Wu, Wenzhou Xiang, Jin Xu and Tao Li
Mar. Drugs 2025, 23(9), 361; https://doi.org/10.3390/md23090361 - 19 Sep 2025
Viewed by 232
Abstract
Porphyridium purpureum can synthesize a high phycoerythrin content, which has strong potential application in nutrition, pharmaceuticals, and cosmetics. An effective culture strategy is the key to producing biomass of P. purpureum rich in phycoerythrin. However, there are still bottlenecks in the large-scale production [...] Read more.
Porphyridium purpureum can synthesize a high phycoerythrin content, which has strong potential application in nutrition, pharmaceuticals, and cosmetics. An effective culture strategy is the key to producing biomass of P. purpureum rich in phycoerythrin. However, there are still bottlenecks in the large-scale production of Porphyridium, such as nutrient supplementation and cultivation mode. In this study, P. purpureum SCS-02, isolated from the South China Sea, was used as experimental microalga strain. The effects of different salinity (10, 20 and 34 ppt) and semi-continuous culture on accumulation of biomass and phycoerythrin were investigated. The semi-continuous culture modes include recycled culture medium mode (RM) and fresh culture medium mode (FM). The results showed that low salinity (10 ppt) could enhance the accumulation of phycoerythrin, the content and yield of which were 8.39% DW and 160 mg L−1, respectively. The yield of phycoerythrin of P. purpureum in semi-continuous culture with a 30% renewal rate of fresh culture medium was 253% higher than the batch culture. In summary, the semi-continuous culture strategy with fresh medium renewal under low salinity conditions increased the phycoerythrin yield to 641.47 mg after 30 days of cultivation, while exopolysaccharide accumulation was significantly reduced compared with batch culture. These results provide useful reference for optimizing culture strategies of P. purpureum, and may serve as a basis for future attempts to scale phycoerythrin production under industrially relevant conditions. Full article
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15 pages, 2900 KB  
Article
Co-Culture of Auxenochlorella protothecoides and Serratia liquefaciens Promotes Lutein Accumulation
by Weiwei Xue, Zhen Li, Yanhong Qiu, Yong Ma, Yongchang Xue, Zongshen Zhang and Changbin Liu
Mar. Drugs 2025, 23(9), 360; https://doi.org/10.3390/md23090360 - 18 Sep 2025
Viewed by 196
Abstract
Lutein, a crucial carotenoid with diverse biological roles, is in high demand in the market. Current production predominantly relies on plant extraction, which is hindered by low yield and seasonal limitations. Microalgae, such as Chlorella and Chlamydomonas, known for their efficient lutein production [...] Read more.
Lutein, a crucial carotenoid with diverse biological roles, is in high demand in the market. Current production predominantly relies on plant extraction, which is hindered by low yield and seasonal limitations. Microalgae, such as Chlorella and Chlamydomonas, known for their efficient lutein production due to high photosynthetic efficiency, rapid growth, and ease of cultivation, still require enhanced yields. This study presents a novel finding that co-cultivating A. protothecoides with S. liquefaciens significantly boosts lutein production. Optimization of carbon and nitrogen sources, nitrogen-to-phosphorus (N:P) ratio, and algal-bacterial inoculation ratio using BG11 medium was systematically conducted. The results indicate that supplementing with 3.0 g/L sodium acetate as the carbon source, 2.0 g/L sodium nitrate as the nitrogen source, sodium dihydrogen phosphate to achieve an N:P ratio of 12:1, and an algal:bacterial inoculation ratio of 10:1, resulted in an A. protothecoides biomass of 21.72 g/L (DWt) and a lutein yield significantly increased to 56.86 mg/g (DWt), a ninefold rise compared to monoculture. This co-cultivation approach offers a promising avenue for sustainable industrial lutein production. Full article
(This article belongs to the Special Issue Marine Algal Biotechnology and Applications—2nd Edition)
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22 pages, 2267 KB  
Article
Contamination Characteristics of 21 PFAS in Shellfish and Crustaceans of Zhejiang Province and Exposure Risk Assessment for Adult Dietary Consumers
by Hexiang Zhang, Haoyi Zhang, Ronghua Zhang, Dong Zhao, Bing Zhu, Xiaojuan Qi, Lili Chen, Jiang Chen, Jikai Wang, Yibin Zheng and Zhewei Feng
Mar. Drugs 2025, 23(9), 359; https://doi.org/10.3390/md23090359 - 15 Sep 2025
Viewed by 426
Abstract
This study investigated the occurrence, sources, and health risks of 21 per- and polyfluoroalkyl substances (PFAS) in commercially available shellfish and crustaceans from Zhejiang Province, China. Among the 306 samples analyzed, 87.9% contained at least one detectable PFAS. Perfluorooctanoic acid (PFOA) was the [...] Read more.
This study investigated the occurrence, sources, and health risks of 21 per- and polyfluoroalkyl substances (PFAS) in commercially available shellfish and crustaceans from Zhejiang Province, China. Among the 306 samples analyzed, 87.9% contained at least one detectable PFAS. Perfluorooctanoic acid (PFOA) was the most frequently detected PFAS (64.7%), followed by perfluorooctanesulfonic acid (PFOS) (53.8%), perfluorononanoic acid (PFNA) (52.9%), and perfluorodecanoic acid (PFDA) (50.0%). The total PFAS in shellfish and crustaceans ranged from ND to 0.86 to 173 ng/g wet weight, with a median of 4.11 ng/g ww; the median concentration of total PFAS followed this order: marine crustaceans > fresh-water crustaceans > bivalves. Estimation of the human intake of adult consumers, the estimated daily intake (EDI) of Σ21 PFAS ranged from 0.01 to 15.7 ng/kg bw/day; 0.31% of the adult study population had Σ4PFAS exposure levels resulting in Hazard Quotient (HQ) values > 1, which may represent a potential public health concern for these individuals. Long-term exposure risks for specific PFCAs such as perfluoroundecanoic acid (PFUdA) and perfluorotridecanoic acid (PFTrDA) merit concern. Full article
(This article belongs to the Section Marine Toxins)
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17 pages, 2211 KB  
Article
Single-Cell Transcriptomic Analysis Reveals Cell Heterogeneity and Altered Signaling Pathways in Jellyfish Sting Patients
by Zhen Qin, Zhengfeng Hao, Chun Wang, Ning Lu, Peiju Qiu, Su Wang and Rilei Yu
Mar. Drugs 2025, 23(9), 358; https://doi.org/10.3390/md23090358 - 15 Sep 2025
Viewed by 387
Abstract
Jellyfish stings induce a range of symptoms, from localized irritation to life-threatening systemic reactions, yet the underlying immune mechanisms remain poorly understood. This study employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from a severely affected patient and healthy [...] Read more.
Jellyfish stings induce a range of symptoms, from localized irritation to life-threatening systemic reactions, yet the underlying immune mechanisms remain poorly understood. This study employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from a severely affected patient and healthy controls, uncovering the immune landscape at single-cell resolution and identifying the signaling pathways. We identified 11 major immune cell types, with a marked increase in CD14+ monocytes (81.86% of total cells) and significant reductions in T cells, B cells, and CD16+ monocytes in the envenomated patient. Subclustering revealed six monocyte and four neutrophil subsets, each displaying distinct functional profiles. Patient monocytes were enriched for MMP9+ and RETN+ subsets, associated with leukocyte migration and inflammation, whereas healthy controls exhibited CD74+ monocytes linked to oxidative phosphorylation. Neutrophils in the patient were predominantly LTF+ and S100A12+, implicating inflammatory and immune regulatory pathways. These findings provide a detailed single-cell atlas of immune dysregulation post-jellyfish sting, highlighting the pivotal roles of MMP9+ monocytes and S100A12+ neutrophils in driving inflammation. This study offers potential therapeutic targets for mitigating severe immune responses in jellyfish envenomation. Full article
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17 pages, 28303 KB  
Article
Design and Synthesis of Marine-Inspired Itampolin A Derivatives to Overcome Chemoresistance in NSCLC via Cholesterol Homeostasis Modulation
by Hai-Ying Zhang, Shun-Chang Ji, Si-Hua Xie, Yu Chen, Cai-Xia Lin, Xu Huang, Yi-Qiao Wang, Jing-Wei Liang and Yan Liu
Mar. Drugs 2025, 23(9), 357; https://doi.org/10.3390/md23090357 - 15 Sep 2025
Viewed by 346
Abstract
Recent studies on brominated tyrosine-derived marine natural products have significantly expanded the library of known structures and revealed their potent and diverse antitumor mechanisms. Building upon our previous research on the natural product itampolin A isolated from marine sponges, we conducted structural optimizations [...] Read more.
Recent studies on brominated tyrosine-derived marine natural products have significantly expanded the library of known structures and revealed their potent and diverse antitumor mechanisms. Building upon our previous research on the natural product itampolin A isolated from marine sponges, we conducted structural optimizations and explored the structure–-activity relationships (SARs) of novel scaffold derivatives concerning their inhibitory activities against lung cancer cells. In the present study, we further synthesized 15 novel derivatives, and compound 4l demonstrated selective anti-proliferative activity against gefitinib-resistant PC9/GR cells, showing 4-fold greater potency compared to parental PC9 cells. Building on this finding, the present study aims to investigate the molecular mechanisms underlying the anti-proliferative effects of 4l in drug-resistant NSCLC models. Through cell cycle analysis, apoptosis assays, and signaling pathway evaluation, we seek to establish a theoretical foundation for developing novel therapeutic agents against chemotherapy-resistant lung cancer. Full article
(This article belongs to the Special Issue Bio-Active Components from Marine Sponge)
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18 pages, 5407 KB  
Article
Improvement Effect and Regulation Mechanism of Oyster Peptide on Dexamethasone-Induced Osteoporotic Rats
by Wei Yang, Wenyu Ma, Xiaoming Qin, Wenhong Cao and Haisheng Lin
Mar. Drugs 2025, 23(9), 356; https://doi.org/10.3390/md23090356 - 11 Sep 2025
Viewed by 438
Abstract
The increasing global population of the elderly and rising life expectancy have made osteoporosis a more severe public health issue, necessitating the development of safer and more effective therapeutic strategies. This study investigated the osteoprotective effects of low, medium, and high doses of [...] Read more.
The increasing global population of the elderly and rising life expectancy have made osteoporosis a more severe public health issue, necessitating the development of safer and more effective therapeutic strategies. This study investigated the osteoprotective effects of low, medium, and high doses of oyster peptide (OP) in dexamethasone (DEX)-induced osteoporotic rats. Pathological analysis showed that OP treatment effectively mitigated bone loss and repaired bone microarchitecture deterioration caused by DEX administration. In the OP groups, levels of the osteogenic markers osteocalcin (OCN) and osteoprotegerin (OPG) were significantly higher than in the DEX group. Moreover, levels of the osteoclastic markers RANKL, Cathepsin K (Cath-K), MMP-9, C-terminal telopeptide of type I collagen (CTX-1), and Deoxypyridine (DPD) were significantly lower. Bone proteomic analysis of the DEX and OP groups revealed that differentially expressed proteins were significantly enriched in pathways related to extracellular matrix and structural reorganization, ECM–receptor interaction, and PI3K-Akt signaling. Furthermore, virtual screening simulations indicated that peptides with lengths ranging from 11 to 20 amino acid residues were involved in modulating the activity of key receptors in these pathways, including Integrins α5β1, Integrins αvβ3, and EGFR. Collectively, these results demonstrate the significant potential of OP as a novel therapeutic agent for osteoporosis. Full article
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14 pages, 807 KB  
Article
Phycobiliprotein Extract from Arthrospira platensis Boosts Immune Function in Pacific Oysters (Magallana gigas)
by Aleksandra Andreyeva, Tatyana Kukhareva, Anastasiya Tkachuk, Maria Podolskaya, Elina Chelebieva and Andrey Borovkov
Mar. Drugs 2025, 23(9), 355; https://doi.org/10.3390/md23090355 - 10 Sep 2025
Viewed by 367
Abstract
The utilization of functional feeds in oyster hatcheries to reduce disease-related issues and improve health in the prespawning period is expected to become essential in the near future. In the present study, an aqueous extract of phycobiliproteins (CBPs) sourced from the cyanobacterium Arthrospira [...] Read more.
The utilization of functional feeds in oyster hatcheries to reduce disease-related issues and improve health in the prespawning period is expected to become essential in the near future. In the present study, an aqueous extract of phycobiliproteins (CBPs) sourced from the cyanobacterium Arthrospira platensis was tested as an immunomodulatory agent in the Pacific oyster (Magallana gigas). Adult oysters were given three distinct treatments with the aqueous extract of CBPs (2, 20 or 80 μg/mL) for 24–96 h. In vivo analysis demonstrated that the extract of CBPs enhanced phagocytosis, lysosomal content and mitochondrial membrane potential levels, but inhibited the production of reactive oxygen species in hemocytes of oysters. Higher concentrations of the extract (80 μg/mL) had a more rapid effect on phagocytosis, with significant differences found after the first 24 h of the experiment. Lower concentrations of the extract (2 μg/mL) enhanced the phagocytic activity of hemocytes at later stages of its administration. Additionally, the expression profiles of the hsp70 and hsp90 genes were monitored in gills from oysters exposed to the extract at concentrations of 2, 20 and 200 μg/mL for 48 h, considering their roles in regulating the innate immune system in bivalves. The results show that hsp70 expression was down-regulated during the first 24 h of administration, whereas it recovered to control levels after 48 h. In contrast, the expression levels of hsp90 were up-regulated throughout the entire period of extract administration. Combined, the results of the present study show that the aqueous extract of CBPs from A. platensis can rapidly enhance the cellular immune response in Pacific oysters, and could potentially be used as an immunomodulator in bivalve hatcheries. Full article
(This article belongs to the Special Issue Immunomodulatory Activities of Marine Products)
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19 pages, 2207 KB  
Article
Salinity Modulates Carbon Flux to Promote Squalene and PUFA Biosynthesis in the Marine Protist Thraustochytrium
by Yuetong Zhao, Xingyu Zhu, Nimra Riaz, Xiuping Liu, Jiaqian Li and Guangyi Wang
Mar. Drugs 2025, 23(9), 354; https://doi.org/10.3390/md23090354 - 30 Aug 2025
Viewed by 798
Abstract
Salinity is a key environmental factor regulating lipid metabolism in marine oleaginous protists. This study examined the impact of NaCl concentration on growth, glucose utilization, and lipid biosynthesis in Thraustochytrium sp. ATCC 26185. Moderate salinity (20 g/L) enhanced biomass and glucose uptake, while [...] Read more.
Salinity is a key environmental factor regulating lipid metabolism in marine oleaginous protists. This study examined the impact of NaCl concentration on growth, glucose utilization, and lipid biosynthesis in Thraustochytrium sp. ATCC 26185. Moderate salinity (20 g/L) enhanced biomass and glucose uptake, while high salinity (45 g/L) induced osmotic stress yet significantly promoted squalene accumulation (17.27 mg/g), a 3.26-fold increase compared with 0 g/L NaCl (5.29 mg/g). Integrated transcriptomic and metabolomic analyses revealed that salinity-dependent activation of glycolysis, the TCA cycle, and the pentose phosphate pathway increased cellular ATP, NADH, and NADPH levels. Under salt stress, the mevalonate (MVA) pathway was transcriptionally upregulated, with key enzymes, including ACAT, HMGR, and IDI, showing marked induction, which supports enhanced carbon flux toward squalene biosynthesis. Despite SQS downregulation, squalene accumulation increased, likely due to elevated precursor availability and reduced flux to downstream sterol pathways. Concurrently, high salinity repressed expression of ACC, FAS-α, and FAS-β, reducing saturated fatty acid levels, while upregulation of PKSB-favored polyunsaturated fatty acid (PUFA) synthesis. These findings suggest that high-salt stress triggers transcriptional reprogramming, redirecting acetyl-CoA from fatty acid synthesis toward squalene and PUFA production. This study offers new insights into the metabolic plasticity of thraustochytrids and highlights salinity modulation as a promising strategy for enhancing high-value lipid yields in marine biotechnology. Full article
(This article belongs to the Special Issue Advances in Natural Products of Marine Thraustochytrids)
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1 pages, 3790 KB  
Article
Secondary Metabolites of the Marine Sponge-Derived Fungus Aspergillus subramanianii 1901NT-1.40.2 and Their Antimicrobial and Anticancer Activities
by Olga O. Khmel, Anton N. Yurchenko, Phan Thi Hoai Trinh, Ngo Thi Duy Ngoc, Vo Thi Dieu Trang, Huynh Hoang Nhu Khanh, Alexandr S. Antonov, Konstantin A. Drozdov, Roman S. Popov, Natalya Y. Kim, Dmitrii V. Berdyshev, Ekaterina A. Chingizova, Ekaterina S. Menchinskaya and Ekaterina A. Yurchenko
Mar. Drugs 2025, 23(9), 353; https://doi.org/10.3390/md23090353 - 30 Aug 2025
Viewed by 1110
Abstract
The aim of this study was to investigate the metabolites in Aspergillus subramanianii 1901NT-1.40.2 extract using UPLC-MS, isolate and elucidate the structure of individual compounds, and study the antimicrobial and cytotoxic activities of the isolated compounds. The structures of two previously unreported ergostane [...] Read more.
The aim of this study was to investigate the metabolites in Aspergillus subramanianii 1901NT-1.40.2 extract using UPLC-MS, isolate and elucidate the structure of individual compounds, and study the antimicrobial and cytotoxic activities of the isolated compounds. The structures of two previously unreported ergostane triterpenoid aspersubrin A (1) and pyrazine alkaloid ochramide E (2) were established using NMR and HR ESI-MS. The absolute configuration of 1 was determined using quantum chemical calculations. Moreover, the known polyketides sclerolide (3) and sclerin (4); the indolediterpene alkaloid 10,23-dihydro-24,25-dehydroaflavinine (5); the bis-indolyl benzenoid alkaloids kumbicin D (6), asterriquinol D dimethyl ether (7), petromurin C (8); and the cyclopentenedione asterredione (9) were isolated. The effects of compounds 3-9 on the growth and biofilm formation of the yeast-like fungus Candida albicans and the bacteria Staphylococcus aureus and Escherichia coli were investigated. Compounds 5 and 6 inhibited C. albicans growth and biofilm formation at an IC50 of 7–10 µM. Moreover, the effects of compounds 3-9 on non-cancerous H9c2 cardiomyocytes, HaCaT keratinocytes, MCF-10A breast epithelial cells, and breast cancer MCF-7 and MDA-MB-231 cells were also investigated. Compound 8 (10 µM) significantly decreased the viability of MCF-7 cells, inhibited colony formation, and arrested cell cycle progression and proliferation in monolayer culture. Moreover, 8 significantly decreased the area of MCF-7 3D spheroids by approximately 30%. A competitive test with 4-hydroxytamoxyfen and molecular docking showed that estrogen receptors (ERβ more than ERα) were involved in the anticancer effect of petromurin C (8). Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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46 pages, 879 KB  
Review
Analytical Approaches to the Rapid Characterisation of Marine Glycolipids in Bioproduct Discovery
by Sudarshan Dhakal, Tim D. Nalder, Susan N. Marshall and Colin J. Barrow
Mar. Drugs 2025, 23(9), 352; https://doi.org/10.3390/md23090352 - 30 Aug 2025
Viewed by 871
Abstract
Glycolipids are structurally diverse amphiphilic molecules with potential as non-petrochemical-derived bioproducts, including surfactants, emulsifiers, and antioxidants. The different bioactivities associated with this range of glycolipid structures also present opportunities for dietary supplements, cosmetics, and pharmaceuticals. Marine glycolipids are underexplored due to challenges with [...] Read more.
Glycolipids are structurally diverse amphiphilic molecules with potential as non-petrochemical-derived bioproducts, including surfactants, emulsifiers, and antioxidants. The different bioactivities associated with this range of glycolipid structures also present opportunities for dietary supplements, cosmetics, and pharmaceuticals. Marine glycolipids are underexplored due to challenges with purification and structural characterisation. Analytical approaches enabling efficient sample purification, isolation, and identification of target glycolipids are crucial to determining the bioactivity and functions of organisms such as shellfish and seaweed. This review summarises advances in analytical methods applicable to marine glycolipids, including extraction and enrichment methods tailored to specific subclasses. Thin-layer chromatography (TLC)-based rapid detection techniques developed for specific subclasses in complex biological samples are discussed, alongside structure identification methods based on liquid chromatography (LC)–electrospray ionisation (ESI)–tandem mass spectrometry (MS/MS). Hydrophilic interaction liquid chromatography (HILIC), reverse-phase liquid chromatography (RPLC), and supercritical fluid chromatography (SFC) coupled with MS detection are reviewed for their application to glycolipids. The application of two-dimensional liquid chromatography (2D-LC) and advanced MS-based approaches that facilitate both the rapid resolution and comprehensive characterisation of molecular species are also reviewed. Full article
(This article belongs to the Special Issue From Marine Natural Products to Marine Bioproducts)
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29 pages, 3932 KB  
Review
Overview of Primary and Secondary Metabolites of Rugulopteryx okamurae Seaweed: Assessing Bioactivity, Scalability, and Molecular Mechanisms
by Ana Minerva García-Cervantes, José A. M. Prates and José Luis Guil-Guerrero
Mar. Drugs 2025, 23(9), 351; https://doi.org/10.3390/md23090351 - 30 Aug 2025
Viewed by 989
Abstract
Rugulopteryx okamurae is an invasive brown alga that has colonised Mediterranean and northeastern Atlantic coastlines, posing significant ecological and economic challenges. Its biomass is rich in structurally diverse metabolites—including polysaccharides (alginate, fucoidan, laminaran), phlorotannins, diterpenoids, fatty acids, and peptides—many of which exhibit notable [...] Read more.
Rugulopteryx okamurae is an invasive brown alga that has colonised Mediterranean and northeastern Atlantic coastlines, posing significant ecological and economic challenges. Its biomass is rich in structurally diverse metabolites—including polysaccharides (alginate, fucoidan, laminaran), phlorotannins, diterpenoids, fatty acids, and peptides—many of which exhibit notable antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Comparative assessment of extraction yields, structural features, and bioactivity data highlights phlorotannins and diterpenoids as particularly promising, demonstrating low-micromolar potencies and favourable predicted interactions with key inflammatory and apoptotic targets. Algal polysaccharides exhibit various bioactivities but hold strong potential for scalable and sustainable industrial applications. Emerging compound classes such as fatty acids and peptides display niche bioactivities; however, their structural diversity and mechanisms of action remain insufficiently explored. Insights from in vitro and in silico studies suggest that phlorotannins may modulate NF-κB and MAPK signalling pathways, while diterpenoids are implicated in the induction of mitochondrial apoptosis. Despite these findings, inconsistent extraction methodologies and a lack of in vivo pharmacokinetic and efficacy data limit translational potential. To overcome these limitations, standardized extraction protocols, detailed structure–activity relationship (SAR) and pharmacokinetic studies, and robust in vivo models are urgently needed. Bioactivity-guided valorisation strategies, aligned with ecological management, could transform R. okamurae biomass into a sustainable source for functional foods, cosmetics, and pharmaceuticals applications. Full article
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25 pages, 662 KB  
Review
Anti-Inflammatory and Neuroprotective Effects of Undaria pinnatifida Fucoidan
by Cheng Yang, Corinna Dwan, Barbara C. Wimmer, Sayed Koushik Ahamed, Fionnghuala James, Jigme Thinley, Richard Wilson, Luke Johnson and Vanni Caruso
Mar. Drugs 2025, 23(9), 350; https://doi.org/10.3390/md23090350 - 29 Aug 2025
Viewed by 1343
Abstract
Undaria pinnatifida fucoidan (UPF), a sulphated polysaccharide derived from brown seaweed, has attracted scientific and clinical interest for its wide-ranging anti-inflammatory and neurodegenerative properties. A growing body of research shows that UPF inhibits NF-κB and MAPK signalling pathways, reduces pro-inflammatory cytokines (TNF-α, IL-1β, [...] Read more.
Undaria pinnatifida fucoidan (UPF), a sulphated polysaccharide derived from brown seaweed, has attracted scientific and clinical interest for its wide-ranging anti-inflammatory and neurodegenerative properties. A growing body of research shows that UPF inhibits NF-κB and MAPK signalling pathways, reduces pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), decreases ROS production, and suppresses iNOS and COX-2 activity, thereby mitigating oxidative and inflammatory damage in vitro. In vivo studies confirm these actions, demonstrating reduced systemic inflammation, promoted antioxidant defence, modulated gut microbiota composition, and improved production of beneficial microbial metabolites. In parallel, emerging evidence highlights UPF’s neuroprotective potential, characterised by protection against neuroinflammation and oxidative stress, the attenuation of amyloid-beta deposition, and improvement in neuronal function. Importantly, low- to medium-molecular-weight and highly sulphated UPF fractions consistently exhibit stronger bioactivities, suggesting a structural basis for its therapeutic potential. This review integrates mechanistic evidence from cellular, preclinical, and emerging clinical studies, highlighting UPF as a versatile marine-derived agent with therapeutic relevance for inflammatory and neurodegenerative diseases, and outlines future research directions toward clinical translation. Full article
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20 pages, 8884 KB  
Article
Haemostatic and Biocompatibility Evaluation of Alginate-Functionalized Polylactide Composite Containing Zinc Sulphide and Hardystonite
by Anna Kaczmarek, Zdzisława Mrozińska, Jerzy J. Chruściel, Michał Juszczak, Katarzyna Woźniak and Marcin H. Kudzin
Mar. Drugs 2025, 23(9), 349; https://doi.org/10.3390/md23090349 - 29 Aug 2025
Viewed by 668
Abstract
The aim of this study was to evaluate the haemostatic potential and biocompatibility of a newly developed composite material for its use in blood-contacting applications. Based on promising reports on polylactide (PLA), sodium alginate (ALG), and bioactive additives such as hardystonite (HT) and [...] Read more.
The aim of this study was to evaluate the haemostatic potential and biocompatibility of a newly developed composite material for its use in blood-contacting applications. Based on promising reports on polylactide (PLA), sodium alginate (ALG), and bioactive additives such as hardystonite (HT) and zinc sulphide (ZnS), a melt-blown PLA nonwoven was modified via dip-coating using an ALG solution as a matrix for incorporating HT and ZnS particles, resulting in the PLA-ALG-ZnS-HT composite. The material was characterised in terms of surface morphology, specific surface area, pore volume, average pore size, and zeta potential (pH~7.4). Haemostatic activity was assessed by measuring blood coagulation parameters, while biocompatibility was evaluated through the viability of human peripheral blood mononuclear (PBM) cells and human foreskin fibroblasts (Hs68). Genotoxicity was analysed using the comet assay and plasmid relaxation test. Results confirmed a uniform alginate coating with dispersed HT and ZnS particles on PLA fibres. The modification increased the surface area and pore volume and caused a shift toward less negative zeta potential. Haemostatic testing showed prolonged activated partial thromboplastin time (aPTT), likely due to Zn2+ interactions with clotting factors. Biocompatibility tests showed high cell viability and no genotoxic effects. Our findings suggest that the PLA-ALG-ZnS-HT composite is safe for blood and skin cells and may serve as an anticoagulant material. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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16 pages, 4141 KB  
Article
Selective Utilization of Polyguluronate by the Human Gut Bacteroides Species
by Nuo Liu, Ming Li, Xiangting Yuan, Tianyu Fu, Youjing Lv and Qingsen Shang
Mar. Drugs 2025, 23(9), 348; https://doi.org/10.3390/md23090348 - 29 Aug 2025
Viewed by 857
Abstract
Human gut Bacteroides species play crucial roles in the metabolism of dietary polysaccharides. Polyguluronate (PG), a major component of alginate, has been widely used in the food and medical industries. However, how PG is utilized by human gut Bacteroides species has not been [...] Read more.
Human gut Bacteroides species play crucial roles in the metabolism of dietary polysaccharides. Polyguluronate (PG), a major component of alginate, has been widely used in the food and medical industries. However, how PG is utilized by human gut Bacteroides species has not been fully elucidated. Here, using a combination of culturomics, genomics, and state-of-the-art analytical techniques, we elucidated in detail the utilization profiles of PG by 17 different human gut Bacteroides species. Our results indicated that each Bacteroides species exhibited a unique capability for PG utilization. Among all species tested, Bacteroides xylanisolvens consumed the highest amount of PG and produced the greatest quantity of short-chain fatty acids, suggesting that it may be a keystone bacterium in PG utilization. Mass spectrometry showed that PG was degraded by B. xylanisolvens into a series of oligosaccharides. Genomic analyses confirmed that B. xylanisolvens possesses a large and divergent repertoire of carbohydrate-active enzymes. Moreover, genomic annotation identified two enzymes, PL17_2 and PL6_1, in B. xylanisolvens that are potentially responsible for PG degradation. Altogether, our study provides novel insights into PG utilization by human gut Bacteroides species, which has important implications for the development of carbohydrate-based drugs from marine resources. Full article
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23 pages, 3393 KB  
Review
Unlocking the Potential of Red Seaweeds: A Special Focus on Grateloupia turuturu Yamada and Porphyra umbilicalis Kütz
by João Ferreira, Mário Pacheco, Amélia M. Silva and Isabel Gaivão
Mar. Drugs 2025, 23(9), 347; https://doi.org/10.3390/md23090347 - 29 Aug 2025
Viewed by 899
Abstract
Earth hosts a remarkable diversity of life, with oceans covering over 70% of its surface and supporting the greatest abundance and variety of species, including a vast range of seaweeds. Among these, red seaweeds (Rhodophyta) represent the most diverse group and are particularly [...] Read more.
Earth hosts a remarkable diversity of life, with oceans covering over 70% of its surface and supporting the greatest abundance and variety of species, including a vast range of seaweeds. Among these, red seaweeds (Rhodophyta) represent the most diverse group and are particularly rich in bioactive compounds. Grateloupia turuturu Yamada and Porphyra umbilicalis Kütz. are two species with significant biotechnological and functional food potential. They contain high levels of phycobiliproteins, sulfated polysaccharides (e.g., carrageenan, agar, porphyran), mycosporine-like amino acids (MAAs), phenols, minerals, and vitamins, including vitamin B12 (rare among non-animal sources). Several analytical methods, such as spectrophotometry, chromatography, and mass spectrometry, have been used to characterize their chemical composition. In vitro and in vivo studies have demonstrated their antioxidant, anti-inflammatory, neuroprotective, immunostimulatory, anti-proliferative, and photoprotective effects. These bioactive properties support its application in the food, pharmaceutical, and cosmetic sectors. Given the growing demand for sustainable resources, these algae species stand out as promising candidates for aquaculture and the development of functional ingredients. Their incorporation into novel food products, such as snacks and fortified dairy and meat products, underscores their potential to support health-promoting diets. This review highlights G. turuturu and P. umbilicalis chemical richness, bioactivities, and applications, reinforcing their value as sustainable marine resources. Full article
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18 pages, 324 KB  
Review
Harnessing Marine Algae for Sustainable Agriculture: Natural Bioactive Compounds as Eco-Friendly Pesticidal Agents
by Georgi Beev, Diyana Dermendzhieva, Zvezdelina Yaneva, Georgi Kalaydzhiev, Nikolina Naydenova, Daniela Stoeva, Denitsa Georgieva, Silviya Hristova, Zornitsa Beeva and Nikolay Petrov
Mar. Drugs 2025, 23(9), 346; https://doi.org/10.3390/md23090346 - 28 Aug 2025
Viewed by 883
Abstract
Currently, marine algae are capturing the attention of both farmers and researchers eager to integrate sustainable methods to safeguard their crops. Instead of relying exclusively on synthetic pesticides, which often have negative environmental effects, some growers are now exploring algae-based products in hopes [...] Read more.
Currently, marine algae are capturing the attention of both farmers and researchers eager to integrate sustainable methods to safeguard their crops. Instead of relying exclusively on synthetic pesticides, which often have negative environmental effects, some growers are now exploring algae-based products in hopes of reducing pest pressures. Various natural compounds sourced from algae—such as specific fatty acids and complex sugars—are believed to inhibit pest development, although their precise mechanisms are yet to be fully understood. Furthermore, there is some evidence suggesting that these compounds may bolster the plant’s own immune responses, thus enhancing crop resilience. Despite certain limitations on field applications, various techniques, including spraying, amending soil, or pre-treating seeds, are currently being evaluated. The results from the laboratory present a positive outlook, but implementing these discoveries to ensure consistent efficacy in practical settings is a major challenge. Variables such as climatic fluctuations, product durability, and formulation standards all elevate this complexity. In every instance, the approach of incorporating algae to lessen chemical dependence while securing uniform yields persists in being of interest, particularly in the area of organic or low-input farming. Full article
(This article belongs to the Section Marine Pharmacology)
18 pages, 1566 KB  
Article
Structural and Immunological Insights into the Lipooligosaccharide of the Marine Bacterium Kangiella japonica KMM 3897
by Alina P. Filshtein, Vlada S. Belova, Alexandra S. Kuzmich, Lyudmila A. Romanenko and Maxim S. Kokoulin
Mar. Drugs 2025, 23(9), 345; https://doi.org/10.3390/md23090345 - 28 Aug 2025
Viewed by 703
Abstract
The lipooligosaccharide (LOS) of the marine bacterium Kangiella japonica KMM 3897 was structurally characterized using chemical analysis, NMR spectroscopy, and MALDI-TOF mass spectrometry. The oligosaccharide core consists of a monophosphorylated trisaccharide containing 2-amino-2-deoxy-D-glucose, D-glycero-D-manno-heptose, and 3-deoxy-D-manno-oct-2-ulosonic acid. [...] Read more.
The lipooligosaccharide (LOS) of the marine bacterium Kangiella japonica KMM 3897 was structurally characterized using chemical analysis, NMR spectroscopy, and MALDI-TOF mass spectrometry. The oligosaccharide core consists of a monophosphorylated trisaccharide containing 2-amino-2-deoxy-D-glucose, D-glycero-D-manno-heptose, and 3-deoxy-D-manno-oct-2-ulosonic acid. The penta-acylated lipid A moiety features a glucosamine disaccharide backbone with phosphate groups and amide- and ester-linked primary fatty acids [i11:0 (3-OH)], along with a secondary acyl chain (i11:0 or 11:0). Immunostimulatory assays revealed that K. japonica KMM 3897 LOS induced significantly weaker cytokine production in human peripheral blood mononuclear cells (PBMCs) compared with E. coli LPS. Notably, it exhibited potent antagonistic activity against E. coli LPS-mediated toxicity and suppressed caspase-4 activation in LPS-treated PBMCs. These findings highlight its anti-inflammatory and protective properties. Full article
(This article belongs to the Section Marine Pharmacology)
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17 pages, 5606 KB  
Article
Implantable Bioresorbable Scaffold with Fucosylated Chondroitin Sulfate as a Promising Device for Delayed Stimulation of Hematopoiesis
by Natalia Y. Anisimova, Olga V. Rybalchenko, Natalia S. Martynenko, Georgy V. Rybalchenko, Elena A. Lukyanova, Maria I. Bilan, Anatolii I. Usov, Mikhail V. Kiselevskiy and Nikolay E. Nifantiev
Mar. Drugs 2025, 23(9), 344; https://doi.org/10.3390/md23090344 - 28 Aug 2025
Viewed by 829
Abstract
The aim of this study was to evaluate the prospects of using natural fucosylated chondroitin sulfate (FCS) from the sea cucumber Cucumaria japonica as the active component of an implantable biodegradable scaffold to stimulate hematopoiesis in mice with cyclophosphamide (CPh)-induced myelosuppression. The scaffolds [...] Read more.
The aim of this study was to evaluate the prospects of using natural fucosylated chondroitin sulfate (FCS) from the sea cucumber Cucumaria japonica as the active component of an implantable biodegradable scaffold to stimulate hematopoiesis in mice with cyclophosphamide (CPh)-induced myelosuppression. The scaffolds were based on bioresorbable Fe–Mn–C and Fe–Mn–Pd alloys after equal-channel angular pressing (ECAP). The efficiency of the developed constructs with FCS was compared with the activity of the same scaffolds loaded with recombinant human granulocyte colony stimulating factor, as well as solutions of these active compounds administered subcutaneously after the end of the cyclophosphamide (CPh) course. It was found that implantation of the Fe–Mn–C scaffold loaded with FCS most effectively stimulated hematopoiesis, providing a complex effect. This design of the developed constructs contributed to an increase in the concentration not only of leukocytes and neutrophils, but also platelets in the blood, promoted the proliferation of bone marrow cells, increasing the concentration of Ki-67(+) cells, and contributed to the restoration of the morphology of the animals’ spleen. Full article
(This article belongs to the Special Issue Biologically Active Compounds from Marine Invertebrates 2025)
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26 pages, 399 KB  
Review
Therapeutic and Nutraceutical Potential of Sargassum Species: A Narrative Review
by Alejandra Torres-Narváez, Andrea Margarita Olvera-Ramírez, Karen Castaño-Sánchez, Jorge Luis Chávez-Servín, Tércia Cesária Reis de Souza, Neil Ross McEwan and Roberto Augusto Ferriz-Martínez
Mar. Drugs 2025, 23(9), 343; https://doi.org/10.3390/md23090343 - 28 Aug 2025
Viewed by 1862
Abstract
In the face of agricultural and environmental crises, the ocean and its diverse abundance of species have garnered attention as sources of beneficial compounds for humans, offering sustainable solutions across various sectors with minimal environmental impact. Sargassum, a genus of macroalgae, has [...] Read more.
In the face of agricultural and environmental crises, the ocean and its diverse abundance of species have garnered attention as sources of beneficial compounds for humans, offering sustainable solutions across various sectors with minimal environmental impact. Sargassum, a genus of macroalgae, has long been used in alternative medicine and culinary applications. This genus encompasses a wide variety of species, many of which contain bioactive compounds with significant therapeutic potential that remain under investigation. Some Sargassum species not only represent a valuable resource but also pose challenges due to their overgrowth, making their utilization both essential and strategic. In this narrative review we highlight many of the major physiological effects of these compounds, concentrating on their promising role in addressing global challenges. Full article
25 pages, 3740 KB  
Review
Microalgae-Based 3D Bioprinting: Recent Advances, Applications and Perspectives
by Jinhui Tang, Jiahui Sun, Jinyu Cui, Xiangyi Yuan, Guodong Luan and Xuefeng Lu
Mar. Drugs 2025, 23(9), 342; https://doi.org/10.3390/md23090342 - 27 Aug 2025
Viewed by 987
Abstract
Three-dimensional bioprinting integrating living cells and bioactive materials enables the fabrication of scaffold structures supporting diverse cellular growth and metabolism. Microalgae are among the most promising microbial platforms for the construction of photosynthetic cell factories, while the current industrial-scale cultivation of microalgae remains [...] Read more.
Three-dimensional bioprinting integrating living cells and bioactive materials enables the fabrication of scaffold structures supporting diverse cellular growth and metabolism. Microalgae are among the most promising microbial platforms for the construction of photosynthetic cell factories, while the current industrial-scale cultivation of microalgae remains predominantly dependent on traditional liquid submerged systems, imposing limitations on commercial viability due to both process and economic constraints. Encapsulation of microalgae within bioactive matrices combined with 3D bioprinting to fabricate customized structures has been explored to address the limitations of submerged cultivation, which are expected to expand microalgal applications and establish new research directions in microalgal biotechnology. This review analyzes both matrices and methods of 3D bioprinting, summarizing the advancement of microalgae-based 3D bioprinting into six main domains including living building materials, biophotovoltaics, photosynthetic biosynthesis, bioremediation, tissue engineering, and food engineering. Lastly, synthetic biology-informed perspectives are provided on future developments of 3D bioprinting technologies and their potential in microalgal research. Full article
(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)
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27 pages, 2146 KB  
Article
Giant Moray Eel (Gymnothorax javanicus), a Long-Living Apex Predator That Poses a Food Safety Risk in the Pacific
by Emillie M. F. Passfield, Kirsty F. Smith, D. Tim Harwood, Joshua D. Fitzgerald, Phoebe A. Argyle, Jacob Thomson-Laing and J. Sam Murray
Mar. Drugs 2025, 23(9), 341; https://doi.org/10.3390/md23090341 - 26 Aug 2025
Viewed by 943
Abstract
The giant moray eel (GME; Gymnothorax javanicus) is an important marine species that plays a key ecological role in reef systems and is a valued food source for indigenous communities. However, it is well-known that GMEs pose a food safety risk due [...] Read more.
The giant moray eel (GME; Gymnothorax javanicus) is an important marine species that plays a key ecological role in reef systems and is a valued food source for indigenous communities. However, it is well-known that GMEs pose a food safety risk due to their ability to accumulate high levels of ciguatoxins (CTXs), the toxins known to cause ciguatera poisoning. This study assessed the age, CTX levels, elemental composition, and nutritional profile of seven GME specimens collected from Muri Lagoon, Rarotonga (Cook Islands), representing the most detailed compositional investigation on this species. Age was determined for the three largest specimens, with the oldest being 39 years old. All specimens contained ciguatoxins, with Type I (CTX4A derivatives), Type II (CTX3C derivatives), algal-ciguatoxins, and biotransformed metabolites being detected. There was a higher CTX content in the liver samples compared to flesh samples, with the longest–heaviest specimen containing the highest levels. The CTX1B level observed in flesh samples of all seven eel specimens exceeded the recommended safe guidance level proposed by the USFDA. A similar ciguatoxin profile was observed across flesh sections, with the belly flap or top loin containing the highest levels of CTXs in most specimens. No bioactive metabolites produced by co-occurring harmful microalgae, including regulated shellfish toxins, were detected. Elemental analysis determined the presence of 21 elements, including arsenic, low levels of mercury, and the volcanic elements rubidium and strontium. Nutritionally, the GMEs were shown to be a lean protein source; however, due to the ubiquitous bioaccumulation of CTXs, they pose a food safety risk to consumers. Full article
(This article belongs to the Section Marine Toxins)
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18 pages, 2330 KB  
Article
Total Syntheses of Marine Natural Products Lyngbyabellin O and Lyngbyabellin P
by Jing Chen, Shiyu Li, Chao Xu and Tao Ye
Mar. Drugs 2025, 23(9), 340; https://doi.org/10.3390/md23090340 - 26 Aug 2025
Viewed by 799
Abstract
Lyngbyabellins O and P are complex natural products derived from non-ribosomal peptide synthetase/polyketide synthase (NRPS/PKS) biosynthetic pathways and have been isolated from marine cyanobacterial sources. Both metabolites are characterized by the presence of two thiazole rings and a distinctive dichlorinated β-hydroxy acid [...] Read more.
Lyngbyabellins O and P are complex natural products derived from non-ribosomal peptide synthetase/polyketide synthase (NRPS/PKS) biosynthetic pathways and have been isolated from marine cyanobacterial sources. Both metabolites are characterized by the presence of two thiazole rings and a distinctive dichlorinated β-hydroxy acid side chain. Notably, lyngbyabellin P is further distinguished by the incorporation of a (3R,4S)-statine moiety. Herein, we report the first total syntheses of lyngbyabellins O and P, which are achieved through the convergent coupling of three key synthetic fragments, namely, two enantiomerically enriched thiazole subunits and a hydroxycarboxylic acid derivative, the latter constructed via a stereoselective aldol reaction. The total syntheses were completed in 12 and 13 longest linear steps (LLSs) for lyngbyabellins O and P, respectively, furnishing the natural products in overall yields of 5.6% and 2.5%. Full article
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20 pages, 3513 KB  
Article
New Strategy for the Degradation of High-Concentration Sodium Alginate with Recombinant Enzyme 102C300C-Vgb and the Beneficial Effects of Its Degradation Products on the Gut Health of Stichopus japonicus
by Ziqiang Gu, Feiyu Niu, Peng Yang, Wenling Gong, Hina Mukhtar, Siyu Li, Yanwen Zheng, Yiling Zhong, Hanyi Cui, Jichao Li, Haijin Mou and Dongyu Li
Mar. Drugs 2025, 23(9), 339; https://doi.org/10.3390/md23090339 - 25 Aug 2025
Viewed by 738
Abstract
High viscosity of alginate means a relatively low substrate concentration, which limits the efficiency of hydrolysis, resulting in one of the main challenges for the large-scale production of alginate oligosaccharides (AOS). In this study, a pilot-scale degradation product (PSDP) of the recombinant enzyme [...] Read more.
High viscosity of alginate means a relatively low substrate concentration, which limits the efficiency of hydrolysis, resulting in one of the main challenges for the large-scale production of alginate oligosaccharides (AOS). In this study, a pilot-scale degradation product (PSDP) of the recombinant enzyme 102C300C-Vgb was produced for the first time at a substrate concentration of up to 20% sodium alginate. The optimal conditions for SA digestion were: enzyme dosage of 25 U/g, enzymatic temperature of 45 °C, enzymatic pH of 7.0, and enzymatic time of 24 h. Under these conditions, the yield of enzymatic hydrolysis was consistently in the range of 69% to 70%. The average molecular weight (Mw) of PSDP was 1496.36 Da, mainly containing oligosaccharides with degrees of polymerization ranging from 2 to 4. The low-Mw PSDP was subsequently applied in the diet of sea cucumber Stichopus japonicus. The results showed that the body wall weight of S. japonicus increased significantly after 40 days of feeding with a 0.09% PSDP-supplemented diet. Furthermore, PSDP-supplemented diet significantly increased the thickness of the serosal and submucosal layers and the width folds of mucosa of the sea cucumber gut. The abundance of pathogenic bacteria was reduced effectively, and that of beneficial bacteria increased significantly after being fed with PSDP. The results demonstrated that PSDP can serve as a digestive health enhancer for sea cucumbers, promoting their healthy growth. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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