Marine Drugs最新文献

The worldwide incidence of neurodegenerative diseases (ND), such as dementia, has increased, and neuroinflammation is considered a crucial factor in the development of ND. Codium fragile is considered ocean waste in many countries; however, some countries, including Korea, consume it as a food resource. In this study, a major low-molecular-weight component and chemical marker, uracil, was isolated from the aqueous extracts of C. fragile (AECF); additionally, its content was measured through HPLC quantitative analysis. AECF and uracil were examined for their anti-inflammatory activities against lipopolysaccharide (LPS)-stimulated BV2 microglia and RAW264.7 macrophage cell lines under inflammation conditions. The results showed that AECF and uracil inhibited the production of pro-inflammatory cytokines by suppressing the NF-κB pathway.

Marine flora is a significant source of bioactive metabolites. These compounds have been demonstrated to have outstanding bioactivity and biocompatibility, enabling their use in various therapeutic applications. Therefore, examining the biological potential of marine natural compounds remains important, with particular emphasis on their interaction profiles to identify the macromolecular partners they can modulate. This study focused on the interactome profiling of the marine alkaloid caulerpin (CAU), isolated from the alga Caulerpa cylindracea. Along with the discovery of its antitumor properties, this metabolite has garnered attention for its potential therapeutic applications, including modulation of MAO-B and PPARs involved in inflammatory responses, as well as the discovery of its antitumor properties. Two complementary MS-based proteomic approaches were used to identify CAU target proteins in cancer cells: DARTS, which enabled proteome-wide screening to identify proteins interacting with the compound, and t-LIP-MRM-MS, which pinpointed the target protein regions involved in ligand binding. RUVB-like 1 (RUVBL1), a protein that regulates the essential mechanism of carcinogenesis, including chromatin remodeling, DNA repair, and transcriptional control, was discovered as an intriguing CAU target. These results were corroborated via in silico and biological investigations that elucidated CAU role in the regulation of RUVBL1 activity, highlighting its promising therapeutic relevance.

Fisheries bycatch, while representing a major ecological concern due to the incidental capture of non-target species, also constitutes an underexplored source of marine biomass with biotechnological potential. This study aimed to generate and characterize bioactive peptides from the muscle tissue of three common bycatch species from the Brazilian coast: Paralonchurus brasiliensis, Micropogonias furnieri, and Hepatus pudibundus. Muscle homogenates were hydrolyzed using either Alcalase or Protamex to produce peptide-rich hydrolysates, which were analyzed through SDS-PAGE, HPLC-UV, MALDI-TOF, and LC-MS/MS. De novo sequencing and bioinformatic analyses predicted bioactivities that were subsequently validated by in vitro assays. The results demonstrated that enzyme selection strongly influenced both peptide profiles and bioactivity. The Protamex hydrolysate of P. brasiliensis (PBP) exhibited potent antifungal activity, inhibiting Candida albicans growth by 81%, whereas the Alcalase hydrolysate (PBA) showed moderate inhibition of Staphylococcus aureus (29%). No significant effect was observed against Escherichia coli. Overall, this study highlights a sustainable strategy for the valorization of fisheries bycatch through the production of bioactive marine peptides and identifies P. brasiliensis hydrolyzed with Protamex as a promising source of anti-Candida peptides for pharmaceutical and nutraceutical applications.

Phycobiliproteins are recognized as potential bioactive compounds and described as highly valued natural products for industrial and biotechnological applications. Moreover, they have been observed to possess antioxidant, anticancer/antineoplastic, and anti-inflammatory activities. Therefore, the search for new methods of their extraction and isolation is still ongoing. Foam fractionation, a bubble separation technique that allows amphiphilic molecules to be separated from their aqueous solutions, is a promising but understudied method. The process may be carried out both under mild conditions that are suitable for proteins and also for diluted solutions. This paper presents the results of applying the foam fractionation process to concentrate and separate phycobiliproteins. Allo- and C-phycocyanin from a thermophilic Synechococcus PCC 6715 strain were used in extract form after biomass cultivation and disintegration. Two ways of running the process were investigated: batch mode and continuous mode, the latter of which has not been reported in the literature previously. The results indicate that the method can be applied on a larger scale, as the outcomes of the continuous mode processes were comparable to those of the batch mode. Moreover, the results indicate that the process provides, to a certain extent, the opportunity of separating phycobiliproteins from each other.

Cholinergic dysfunction is a hallmark of Alzheimer's disease (AD), driven by elevated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity that depletes acetylcholine and contributes to amyloid pathology. Current AD treatments face major challenges, including poor brain penetration, short effect duration and safety concerns, highlighting the need for compounds suitable for preventive or earlier-stage intervention. This study investigated marine phytohormones as modulators of cholinergic imbalance, using an integrative strategy encompassing enzymatic assays, QSAR and DFT calculations, molecular docking, molecular dynamics (MD) simulations, and ADMET profiling. Among them, isopentenyl adenine (IPA) and abscisic acid (ABA) showed inhibitory activity against cholinesterases. IPA inhibited both AChE and BChE through distinct mechanisms with noncompetitive inhibition of AChE and competitive inhibition of BChE, while ABA showed selective noncompetitive inhibition of AChE. DFT-based analysis revealed distinct electronic properties supporting differential reactivity. Moreover, IPA interacted with both catalytic and peripheral residues in AChE, and aligned with BChE's active site, while ABA was bound more peripherally. MD simulations confirmed complex-specific conformational stability based on RMSD, RMSF, Rg, and hydrogen bonding analysis. Both compounds showed low off-target potential against serine proteases and favorable predicted ADMET profiles. These results support the potential of marine phytohormones as preventive modulators of cholinergic dysfunction in AD.

A growing body of evidence indicates that artificial manipulation of transcriptional regulation is a powerful approach to activate cryptic biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) in fungi. In this study, one mutant strain MNP-2-OE::veA was constructed by overexpressing the global transcription regulator veA in an Arctic-derived strain Aspergillus sydowii MNP-2. Chemical investigation of the mutant OE::veA resulted in the isolation of one novel polyhydroxy anthraquinone (1) together with nine known metabolites (2-10), which were unambiguously characterized by various spectroscopic methods including 1D and 2D NMR and HR-ESI-MS as well as via comparison with literature data. Biosynthetically, compounds 1 and 10 as new arising chemicals were, respectively, formed by type II polyketide synthase (T2PK) and non-ribosomal peptide synthetase (NRPS), which were silent in the wild-type (WT) strain MNP-2. A bioassay showed that only compound 3 had weak inhibitory effect on human pathogen Candida albicans, with a MIC value of 64 ug/mL, and 4 displayed in vitro weak cytotoxic activity against HCT116 cells (IC₅₀ = 44.47 μM). These results indicate that overexpression of veA effectively awakened the cryptic BGCs in fungal strains and enhanced their structural diversity in natural products.

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

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

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

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