Search Results (1,424)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with elusive etiology and limited therapeutic options, accompanied by potential side effects. In this study, to investigate the therapeutic potential of Antarctic krill oil (AKO) in a dextran sulfate sodium (DSS)-induced mouse colitis model, animal experiments, molecular assays, transcriptomics, metabolomics, and 16S rRNA gene sequencing were conducted. Our results revealed that supplementation of AKO significantly alleviated colitis symptoms, such as weight loss, and inflammatory responses. Moreover, multi-omics analyses demonstrated that AKO inhibited the PI3K/Akt signaling pathway, remodeled beneficial gut microbiota, and reshaped metabolite profiles associated with glycerolphospholipid metabolism. Remarkably, AKO alleviated DSS-induced colitis, accompanied by coordinated changes in the gut microbiota, metabolites, and transcriptome, which were associated with suppression of key inflammatory pathways. These findings present experimental evidence for the potential of AKO as a marine-based nutritional intervention for UC, and offer novel perspectives on microbiota-targeted therapies for inflammatory diseases. Full article

With global restrictions on in-feed antibiotics, sustainable alternatives are urgently needed to combat weaning-induced intestinal dysfunction in piglets. Fucoidan, a bioactive seaweed polysaccharide, exerts beneficial effects on gut health due to its immunomodulatory and prebiotic properties, but its mechanisms in the gastrointestinal tract of piglets remain unclear. This study investigated the effects of dietary fucoidan supplementation on growth performance, intestinal morphology, gut microbiota composition, and microbial metabolites in weaned piglets. The extracted fucoidan was characterized by a sulfate content of 23.7%, a molecular weight of 29.3 kDa, and fucose as the predominant monosaccharide. A total of 48 weaned piglets were randomly divided into two groups (n = 24 per group): a control group and a 500 mg/kg fucoidan treatment group. Growth performance was evaluated throughout the experiment. On day 28, jejunal and colonic tissues were collected to assess mucosal morphology (n = 6 per group), while cecal and colonic contents were collected for analysis of the gut microbiota and bacterial metabolites. Fucoidan supplementation significantly enhanced average daily gain (ADG, p < 0.05) and feed conversion ratio (FCR, p < 0.05) and mitigated diarrhea during the trial. Notably, piglets fed fucoidan exhibited increased villus height compared to controls (p < 0.05). Fucoidan modulated the gut microbiota by increasing cecal microbial diversity (p < 0.05) and shifting bacterial composition. These modifications involved an altered Bacteroidetes/Firmicutes ratio, as well as an enrichment of Prevotellaceae, Lactobacillus, and Lachnospiraceae (p < 0.05). Consistently, metabolite profiling analysis revealed increased cecal concentrations of lactate (p < 0.05) and butyrate (p < 0.05), which were positively associated with the growth of beneficial taxa. These findings demonstrate that fucoidan alleviates weaning-induced intestinal disorders by improving intestinal morphology and modulating gut microbiota and their metabolites. This study provides a strategy for utilizing marine-derived polysaccharides as functional feed additives to enhance animal health. Full article

Cyanobacteria are prolific producers of secondary metabolites, some of which are potent cyanotoxins that threaten ecosystem integrity and human health. Although blooms have been extensively studied in temperate regions, Southeast Asia’s (SEA’s) tropical marine and estuarine ecosystems remain comparatively underexplored despite their ecological richness and socio-economic importance. This review consolidates current knowledge on marine cyanobacteria and cyanotoxins in SEA, drawing on ecological surveys, ecotoxicological studies, and cyanobacterial bloom case reports. Diverse taxa including Trichodesmium, Lyngbya, Oscillatoria, Neolyngbya, and Aliinostoc, have been documented in SEA’s marine waters, many producing cyanotoxins with various toxic effects. Ecotoxicological risks are intensified by monsoonal variability, nutrient enrichment, and climate-driven shifts that collectively amplifies cyanoblooms and toxin production. Detection methods such as PCR-based assays, LC-MS/MS, and biosensor technologies are increasingly applied to identify toxin biosynthesis genes, cryptic species, and novel metabolites. Environmental challenges including eutrophication from wastewater discharge, trophic transfer of toxins, and climate induced shifts in species distribution, further complicates bloom dynamics and management. Mitigating this requires a multi-pronged approach: advancing biosensors for rapid detection, embedding monitoring within predictive climate frameworks, and expanding molecular surveillance to capture cryptic diversity and gene transfer events. Such strategies are essential for environmental management of cyanobacterial blooms in SEA. Full article

Microalgae are recognized as sustainable biofactories for metabolites relevant to nutraceutical, pharmaceutical, and marine drug applications. Nannochloropsis salina is notable for its production of bioactive lipids, including the pharmaceutically relevant omega-3 eicosapentaenoic acid (EPA). Here, we evaluated orange peel extract (OPE), a citrus by-product, as a substrate for mixotrophic cultivation of N. salina within a bioeconomy framework. OPE supplementation triggered dose-dependent physiological responses. Among the tested OPE concentrations, 5% supplementation resulted in the highest total fatty acid content, increasing fatty acids from 24.4% (control) to 30.6% and EPA from 6.4% to 9.8%, whereas 10% OPE maintained biomass pigmentation. Higher OPE levels enhanced antioxidant potential, raising total antioxidant capacity from 4.6 (control) to 6.7 mg/g vitamin C equivalents (with 10% OPE), while the highest concentrations induced metabolic stress, reducing biomass and altering lipid composition. Fourier transform infrared spectroscopy analyses revealed biochemical adjustments consistent with metabolic reorganization, including increased intensities of the amide I and II bands associated with protein-rich structures. Overall, OPE emerges as a cost-effective supplement capable of modulating the biochemical quality of N. salina while valorizing agro-industrial residues. The increases in EPA and antioxidant capacity support the potential of OPE-supplemented cultures as a platform for the production of marine-derived bioactive compounds. Full article

Breast cancer, especially triple-negative breast cancer (TNBC) and endocrine-resistant disease, remains difficult to treat because of limited effective targeted therapies. In this study, we evaluated the antitumor activity and potential mechanism of MHO7, a marine-derived ophiobolin metabolite, in ER-positive ZR-75-30 cells, tamoxifen-resistant LCC2 cells, and TNBC MDA-MB-231 models. MHO7 dose-dependently reduced cell viability, wound closure, and clonogenic growth in ZR-75-30 and LCC2 cells, with IC₅₀ values of 11.53 and 10.43 μM, respectively. MHO7 also promoted apoptotic cell death, accompanied by increased reactive oxygen species accumulation and altered expression of apoptosis-related proteins, including Bcl-2 and caspase-3. N-acetyl-L-cysteine partially attenuated MHO7-induced apoptosis and YAP reduction in MDA-MB-231 cells, suggesting a contribution of oxidative stress. Molecular docking predicted that MHO7 could occupy the conserved TEAD palmitoylation pocket, and subsequent in vitro analyses showed suppression of YAP/TAZ-TEAD signaling, including reduced YAP nuclear accumulation and decreased TEAD4 expression. In an MDA-MB-231 xenograft model, MHO7 significantly inhibited tumor growth, reduced CD31-positive microvessel density, and decreased Hippo pathway-related transcriptional readouts. These findings indicate that MHO7 exerts broad antitumor activity in breast cancer models through oxidative stress-associated apoptosis and modulation of YAP/TAZ-TEAD signaling, supporting its further development as a lead compound for treatment-resistant breast cancer. Full article

Climate change and increasing instability in coastal marine environments have intensified stressors such as elevated temperature, hypoxia, salinity variation, and pollutant exposure, posing major challenges to the survival, health, and culture performance of bivalves. As economically important aquaculture species and key components of coastal ecosystems, bivalves are highly sensitive to environmental fluctuations, making their metabolic responses highly relevant to both physiological adaptation and aquaculture sustainability. Increasing evidence indicates that metabolic remodeling is an important adaptive strategy supporting bivalve tolerance to environmental stress, with amino acid metabolic remodeling emerging as one of its most sensitive and functionally important components. This review summarizes the major response patterns, key pathways, and potential regulatory mechanisms of amino acid metabolism in bivalves under different stress conditions. Different environmental stressors induce distinct yet integrated shifts in amino acid metabolism, including enhanced catabolism, carbon–nitrogen redistribution, osmotic regulation, and antioxidant defense, thereby supporting energy homeostasis and physiological stress tolerance in bivalves. By highlighting amino acid metabolic remodeling as a central mechanism of bivalve adaptation to environmental stress, this review provides insights into adaptive responses, metabolite-based indicators for monitoring aquaculture environments and bivalve health, and management strategies for improving resilience in bivalve aquaculture. Full article

Breast cancer remains a major global health burden. Dactylospongia species have been explored for their cytotoxic potential. This study aims to evaluate the cytotoxic potential of compounds derived from the marine sponge Dactylospongia elegans. Dactylospongia elegans were collected from the Lembeh Strait, macerated using methanol, then partitioned to an ethyl acetate fraction. The cytotoxic activity of these fractions was assessed using MDA-MB-231 cells while toxicity testing was done using the BSLT. TLC was carried out to determine the groups of compounds, while LC-MS/MS was used to predict active compounds contained in the ethyl acetate fractions. In silico studies were conducted as preliminary studies to determine the antitumor mechanism. The ethyl acetate fraction and F4 subfraction of Dactylospongia elegans exhibited cytotoxicity toward MDA-MB-231 cells with IC₅₀ values of 15.72 and 41.76 µg/mL, respectively. The BSLT indicated the strongest toxicity belongs to the F6 subfraction (LC₅₀ = 32.831 µg/mL). TLC analysis confirmed the presence of major secondary metabolites as terpenoids, steroids, and alkaloids, then confirmed with LC-MS/MS including 5-epi-illimaquinone and calciferol. Molecular docking revealed that calciferol exhibited the strongest binding affinity toward tyrosine kinase and p53–MDM2 receptors, with binding energies of −10.13 and −10.28 kcal/mol, respectively. These findings suggest that Dactylospongia elegans contains bioactive constituents with potential anticancer activity, particularly against TNBC. Full article

Antarctic marine-derived fungi represent an underexplored reservoir of bioactive secondary metabolites shaped by extreme environmental pressures. In this study, nine fungal isolates obtained from Antarctic macroalgae, lichens, sponge tissue, and sediments were evaluated for their antimicrobial, anticancer, antibiofilm, and metabolomic profiles. Untargeted LC–MS/MS molecular networking (GNPS) revealed a chemically rich metabolome, dominated by alkaloids, followed by polyketides, meroterpenoids, and diketopiperazines, with Penicillium crustosum (A15A) emerging as a major biosynthetic contributor. The annotation of structurally diverse metabolites, including roquefortines, viridicatin derivatives, andrastins, and multiple diketopiperazines, highlights the metabolic plasticity of Antarctic fungi. Anticancer evaluation indicated cytotoxicity, with Aspergillus awamori (A30), Alternaria malorum (A36), and Cladosporium malorum (A38) displaying activity toward HCT 116 colorectal cancer cells at IC₅₀ ≥ 30 µg/mL. Extracts were screened against methicillin-resistant Staphylococcus aureus (MRSA, COL), methicillin-susceptible S. aureus (MSSA, NCTC8325 4), and Escherichia coli K12, revealing low to no activity against these pathogens. Six of the nine isolates exhibited strong antibiofilm activity without inhibiting planktonic bacterial growth, indicating selective biofilm inhibition against MSSA and meeting the criteria for clinical developmental “hits”. Biofilm inhibition ranged from 81.10% to 98.50%, with A15A showing the highest activity (98.50% at 250 µg/mL), followed by A36 (91.16% at 31.35 µg/mL). Botrytis sp. (A22A), P. chrysogenum (A7), Ulocladium microsporum (A24B), and A30 also demonstrated strong antibiofilm activity (81.10–85.89%). To our knowledge, this is the first report describing antibiofilm activity of Antarctic fungal extracts. Full article

The rapid emergence and dissemination of antimicrobial resistance (AMR) among bacterial pathogens, particularly the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), represents one of the most pressing global public health challenges, contributing to increased morbidity, mortality, and healthcare costs. The limited development of new antibiotic classes over the past two decades has intensified the search for structurally novel antimicrobial agents and adjuvants capable of overcoming multidrug resistance. Natural products continue to serve as an invaluable source of anti-infective drug leads owing to their remarkable structural diversity and broad spectrum of biological activities. Mangrove ecosystems, located at the interface of terrestrial and marine environments, harbor highly diverse microbial communities, including fungi that have evolved under extreme environmental conditions and produce a wide range of unique secondary metabolites. Beyond their ecological significance, mangrove-associated fungi have emerged as prolific producers of bioactive compounds with promising antibacterial activity against multidrug-resistant pathogens. This review comprehensively summarizes recent advances (2018–2026) in the discovery of antibacterial metabolites from mangrove-associated fungi active against ESKAPE pathogens, which discusses their structural diversity, reported antimicrobial activities, and emerging strategies for accelerating natural product discovery, including genome mining, metabolomics, OSMAC, adaptive laboratory evolution, and artificial intelligence-assisted approaches. A total of 139 chemically distinct metabolites (Compounds 1–139) isolated from mangrove-associated fungi are critically reviewed, highlighting their potential as promising leads for the development of next-generation antimicrobial agents against ESKAPE pathogens. Full article

The rapid emergence of multidrug-resistant microbial pathogens has created an urgent need for new antimicrobial agents. Marine organisms are a rich source of structurally diverse bioactive metabolites with therapeutic potential, and the sea cucumber H. scabra contains numerous secondary metabolites that may exhibit favorable predicted interactions with antimicrobial targets. This study aimed to identify potential antimicrobial metabolites from H. scabra using an integrated computational approach. Metabolites were identified by gas chromatography–mass spectrometry (GC–MS) and screened against selected bacterial and fungal target proteins using molecular docking. The top-ranked compounds were further evaluated for pharmacokinetic properties through ADME prediction, while the stability of the protein–ligand complexes was assessed using 100 ns molecular dynamics simulations and MM/GBSA binding free energy calculations. GC–MS analysis tentatively identified sixteen metabolites, among which CID 21820889 and CID 304 exhibited favorable predicted binding interactions with target proteins from Acinetobacter baumannii and Candida albicans, respectively. These compounds also demonstrated acceptable predicted pharmacokinetic properties, stable protein–ligand interactions throughout the simulations, and favorable MM/GBSA binding free energies, supporting the stability of the predicted complexes. Overall, MM/GBSA binding free energies ranged from −35.46 to −47.17 kcal/mol, with CID 441130 exhibiting the most favorable overall binding energy (−47.17 kcal/mol), while CID 21820889 also showed a favorable binding free energy (−44.85 kcal/mol). These findings identify several putatively identified, computationally prioritized metabolites from H. scabra as candidates for further investigation and demonstrate the utility of integrating chemical profiling with computational approaches for the early stage screening of marine natural products. Full article

Examining the relationship between an animal’s diet and physiology is crucial to understanding their responses to environmental change. Dietary-induced physiological variation can influence key life history processes, including growth and reproduction, ultimately affecting individual fitness. Reported here are the plasma biochemical parameters related to energy storage, use and nutritional condition in juvenile white sharks (Carcharodon carcharias) in Eastern Australia. Specifically, we used plasma metabolites (triglyceride, cholesterol and β-hydroxybutyrate), thyroid hormone thyroxine and fatty acid profiles from 50 juvenile white sharks (152–340 cm total length) captured on SMART drumlines in Eastern Australia to examine blood biochemistry and nutritional ecology. Concentrations of triglycerides and β-hydroxybutyrate indicated high energy expenditure likely associated with the broad-scale migration of white sharks along the Australian coast, highlighting the importance of β-hydroxybutyrate as an energy source. Seasonal variation in the triglyceride/cholesterol and ω3/ω6 fatty acid ratio, in conjunction with lower docosahexaenoic acid, suggests that lower-quality prey is consumed during winter months, thereby influencing the nutritional condition of these sharks. Additionally, the positive correlation between thyroxine concentrations and water temperature suggests reduced metabolic activity during cooler months. Such fluxes in food quality and nutritional condition may affect juvenile white sharks’ growth and development rate and future reproductive success. Full article

Marine organisms from deep-sea environments have attracted considerable attention in drug discovery because they produce structurally diverse natural products. However, Norwegian deep-sea ecosystems remain largely unexplored in terms of natural product chemistry and bioactivity. In this study, a deep-sea sponge belonging to the genus Phakellia was selectively collected using a low-impact, remotely operated vehicle approach from the Mohn’s Treasure area in the Norwegian Sea at a depth of 2858 m, representing one of the deepest sponge samples investigated in Norwegian waters to date. Chemical investigation of this specimen resulted in the isolation of three new glycosylated fatty acid amides, phakelliosides A–C (1–3), together with two known compounds, 11-(S)-myxillin B (4) and 11-(S)-myxillin C (5), which were isolated as pure individual compounds from natural sources for the first time, with their absolute configurations unambiguously established. These compounds were isolated using a combination of chromatographic techniques, and the structures of the isolated compounds were elucidated by comprehensive spectroscopic analyses, including 1D and 2D NMR and UHPLC–HRMS data. The absolute configurations were determined by optical rotation analysis following acid hydrolysis. Compounds 1–5 were subjected to preliminary antibacterial screening against Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Pseudomonas aeruginosa at 100 µg/mL. Under the screening conditions, compound 3 produced the lowest OD₆₀₀ value against E. faecalis (OD₆₀₀ = 0.154), whereas generally higher OD₆₀₀ values were observed against the Gram-negative strains. To the best of our knowledge, this is the first report describing the preliminary antibacterial screening of glycosylated fatty acid amides isolated from Norwegian deep-sea organisms. These findings expand current knowledge of the chemical diversity of natural products associated with Norwegian deep-sea sponges. The biosynthetic origin of these metabolites remains unresolved and warrants further investigation. Full article

Rare actinomycetes have emerged as important yet underexplored reservoirs for the discovery of novel bioactive compounds. Microbispora, a genus of rare actinomycetes, is widely distributed across diverse ecological niches, including terrestrial soils, marine-associated environments, plant-associated ecosystems, and insect-derived environments. To date, 81 secondary metabolites have been reported from this genus, encompassing quinones, chromones and chromanones, macrolides, other polyketides, alkaloids, peptides and diketopiperazines, and miscellaneous structural classes. These metabolites display antimicrobial, anticancer, neuroprotective, antiviral, plant growth-promoting, and enzyme inhibitory activities. Beyond systematically cataloging these compounds, this review provides an integrated analysis of their structure–activity relationships (SAR), biosynthetic origins, and biological significance. In addition, the biosynthetic potential of Microbispora is discussed based on reported genomic studies, highlighting the presence of numerous predicted and poorly characterized biosynthetic gene clusters. This review provides an integrative perspective on Microbispora as an underexplored but promising source of structurally diverse and bioactive natural products for drug discovery. Full article

Phlorotannins are the characteristic phenolic metabolites of brown seaweeds and represent one of the most chemically diverse, analytically challenging, and industrially promising classes of marine polyphenols. Unlike terrestrial phenolics, phlorotannins are formed from phloroglucinol units and occur as complex mixtures of fucols, phlorethols, fuhalols, fucophlorethols, eckols, and related oligomeric or polymeric structures whose composition varies strongly with species, tissue, season, habitat, extraction protocol, and purification strategy. This review critically examines brown seaweed phlorotannins across five major dimensions: chemical diversity and species-dependent availability; extraction, enrichment, and sustainable solvent strategies, including natural deep eutectic solvents (NADES); analytical challenges and advances in selective quantification, highlighting the non-specific nature of Folin–Ciocalteu assays and the emerging value of selective qNMR-based quantification; and biological relevance to ageing-associated processes such as oxidative stress, inflammation, glycation, metabolic dysfunction, neurodegeneration, and skin ageing. The review further evaluates translational barriers, including poor standardization, uncertain bioavailability, matrix interference, limited compound-specific standards, and insufficient in vivo and clinical validation. Finally, a phlorotannin-first brown seaweed biorefinery framework is proposed, in which the phenolic fraction is recovered early as a high-value stream before sequential valorization of polysaccharides, proteins, pigments, minerals, and residual biomass. This integrated perspective highlights the need to move from crude “total phenolic” descriptions toward chemically defined, functionally validated, and industrially scalable phlorotannin systems. Full article

Marine-associated polar fungi are promising sources of structurally diverse natural products. To investigate polyketide metabolites from the Antarctic moss-derived fungus Penicillium sp. OUCMDZ-4014, HSQC NMR combined with DeepSAT analysis was used to prioritize fractions enriched in cyclic and aromatic polyketides, and chromane-like metabolites. Chromatographic separation yielded ten resorcylic acid lactone-derived aromatic polyketides, including RAL macrolides, ring-opened esters, and isocoumarins, among which compounds 4–7 were new. Their planar structures were established by HRESIMS and 1D/2D NMR analyses. Their chemical structures including configurations were established by HRESIMS, 1D/2D NMR, ECD calculations, 13C NMR calculations, and DP4+ analysis. Isocoumarins 7–10 displayed diverse levels of α-glucosidase inhibition, with compound 9 being the most active (IC₅₀ = 47.0 ± 3.83 μM). Kinetic analysis indicated noncompetitive inhibition by 9 and mixed-type inhibition by 10. Genome mining revealed a putative res biosynthetic gene cluster containing HR-PKS, NR-PKS, and tailoring-enzyme genes. Compound 1 underwent nonenzymatic conversion into 9 under culture-medium conditions, while trace conversion was also observed during concentration, revealing a chemical link between the RAL macrolide and isocoumarin scaffolds, and highlighting the contribution of post-biosynthetic chemical transformation to fungal polyketide diversification. Full article