Marine Drugs最新文献

The rapid spread of the invasive brown macroalga Rugulopteryx okamurae has caused severe ecological and economic damage along the European coasts. Efforts to mitigate its impact have been largely ineffective, highlighting the need for alternative strategies to valorise this invasive species. This study explores the use of R. okamurae aqueous extract (RO extract) as a natural reducing and stabilizing agent for the green synthesis of gold (Au@RO), silver (Ag@RO), and platinum (Pt@RO) nanoparticles. The synthesized nanoparticles were extensively characterized using ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), X-ray diffraction (XRD), zeta potential analysis, and Fourier-transform infrared spectroscopy (FTIR). The results confirmed the successful formation of spherical and stable nanoparticles. Furthermore, the antioxidant activity of the RO extract was determined before and after the synthesis of the nanoparticles by the determination of the reducing power, total phenolic content and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity. Notably, Pt@RO showed the highest enhancement in antioxidant activity among the nanoparticles synthesized. The findings demonstrate that R. okamurae can be repurposed as a valuable bioresource for the environmentally friendly production of metal nanoparticles with promising applications.

The Isles of Scilly are an archipelago of islands in the far southwest of the UK which contain numerous beds of wild bivalve molluscs which are recreationally harvested for local consumption. However, the islands have never previously been assessed for the presence of harmful algae and their shellfish toxin metabolites which can cause serious human health impacts. This study sought to address these knowledge gaps through the analysis of seawater and shellfish tissues for microalgae and toxins utilizing portable and lab-based microscopy, nanopore sequencing, chemical analysis and immunoassay kits. The study design was affected by the national COVID-19 lockdown which enforced implementation of citizen-led sampling and in-field microscopy. Microscopy and sequencing approaches led to the confirmation of multiple HAB species of concern, including those potentially responsible for production of neurotoxic and diarrhetic shellfish toxins. A portable microscope was successfully utilized in the field for recognition of microalgae and for early warning of potential shellfish toxicity events. Chemical analysis of cockle, clam and mussel samples confirmed the detection of paralytic, diarrhetic and amnesic shellfish toxins, with an unusual okadaic acid group toxin profile reaching a maximum toxicity of approximately half the regulatory limit as defined by EU law. The Sensoreal Alert Lateral Flow Assay was used to screen and highlight samples containing higher concentrations of DSP toxins. Furthermore, Tetrodotoxin was detected for the first time in the UK in cockle and grooved carpet shells. Multiple saxitoxin analogues were also detected in two echinoderm species, with this providing the first ever report of paralytic shellfish toxins in the spiny starfish, Marthasterias glacialis. The toxin profiles in the two species varied significantly with a dominance of GTX4 in Luidia ciliaris as opposed to a dominance of STX in Marthasterias glacialis. Overall, the study showed that a multi-method assessment of a previously unexplored region within the UK territory contained microalgae and toxins of concern to human health, and that a citizen-led programme could be instigated using portable microscopy and rapid toxin testing to assess the early warning for potentially harmful microalgae and toxins in the region, with confirmatory analysis being conducted to establish actual levels of risk for local consumers of seafood.

Four new methionine sulfoxide-containing diketopiperazines, (+)-dysidmetsulfoxide A [(+)-1], (+)-dysidmetsulfoxide B [(+)-2], (+)-dysidmetsulfoxide C [(+)-3] and (-)-dysidmetsulfoxide C [(-)-3], were isolated from the South China Sea sponge Dysidea sp. These compounds represented the first example of diketopiperazines possessing the unit of methionine sulfoxide (MetO) isolated from marine sponges. As it was difficult to determine the configuration of chiral sulfur atom in the thionyl group, the structures with absolute configurations of these compounds were elucidated by spectroscopic analyses and total synthesis. It was noteworthy that the purchased synthetic precursors, Fmoc-L- and Fmoc-D-MetO, were mixtures of epimers, respectively, due to the stereogenic sulfur atom in MetO, which were separated to prepare the optically pure isomers via the method of supercritical fluid chromatography (SFC). In addition, the other four optical isomers [(-)-1, (-)-2, (+)-4 and (-)-4] were also synthesized. Furthermore, (+)-1, (-)-1, (+)-3, (+)-4 and (-)-4 showed potential anti-Parkinson's disease activities in an in vivo zebrafish model.

Astaxanthin is a high-value metabolite with substantial market demand, owing to its potent antioxidant activity and diverse health benefits. Microalgae are considered the primary producers of esterified astaxanthin, yet their industrial-scale cultivation is constrained by low productivity, stress-dependent induction, and challenges in metabolic engineering. This review examines strategies to enhance microalgae-derived esterified astaxanthin production through nanoformulation and modulation of metabolic pathways. We highlight that precise, efficient, and multiplexed genetic modifications of the carotenoid biosynthetic pathway can significantly increase astaxanthin accumulation. Downregulation of competing metabolic routes further improves astaxanthin yields. Additionally, targeted engineering of acyltransferases and lipid metabolism regulators enhances astaxanthin esterification, thereby improving its intracellular stability against oxidative degradation. Modifying lipid metabolism also redirects metabolic fluxes toward altered fatty acid saturation in stored lipids, which increases the bioavailability of esterified astaxanthin. The integration of nanoparticles into cultivation systems represents another promising approach, facilitating improved nutrient delivery and light management, and consequently boosting astaxanthin production. However, the application of genetic engineering and nanotechnology faces challenges such as biosafety legislation, regulatory approval processes, and potential ecological impacts. A synergistic combination of both approaches may help overcome these limitations and maximize astaxanthin production from microalgae.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by cholinergic dysfunction, oxidative/nitrosative stress, and neuroinflammation. Marine green algae Caulerpa racemosa are rich in neuroactive lipids and fatty acid derivatives with reported antioxidant and anti-inflammatory properties. However, their integrated mechanistic potential against AD remains largely underexplored. This study aimed to elucidate the neuroprotective mechanisms of C. racemosa metabolites against AD using integrative metabolomics, network pharmacology, molecular docking, and in vitro validation assays. Untargeted LC-HRMS profiling was performed to identify major metabolites in the ethanolic extract of C. racemosa. Neuroprotective targets were predicted via TargetNet, STRING, and Cytoscape (MCODE, CytoNCA). Functional enrichment was conducted using KEGG, GO (BP, MF, CC), and ClueGO. Molecular docking (CB-Dock2) validated compound-target interactions with ACHE, CHRM1, NOS1, and NOS2. Antioxidant (DPPH) and cholinesterase (AChE/BChE) inhibitory activities were evaluated in vitro. Metabolomic profiling identified lipid-dominant metabolites-oleamide, hexadecanamide, palmitoyl ethanolamide, α-linolenic acid, α-eleostearic acid, and 9-oxo-octadecadienoic acid. Network analysis revealed key AD-related hubs (ACHE, CHRM1, NOS1, NOS2) enriched in cholinergic regulation, arachidonic-acid metabolism, oxidative stress response, and nitric oxide signaling. Docking showed moderate multi-target affinities (-6.0 to -8.4 kcal/mol), with α-linolenic acid, α-eleostearic acid, and oxidized C18 lipids exhibiting the strongest interactions-particularly with ACHE and NOS isoforms. In vitro assays showed moderate antioxidant activity (IC₅₀ = 120.97 ± 10.93 µg/mL) and cholinesterase inhibition (AChE IC₅₀ = 136.48 ± 1.70 µg/mL; BChE IC₅₀ = 145.98 ± 3.28 µg/mL), aligning with predicted multi-target interactions. C. racemosa extract exhibits neuroprotective potential through a synergistic combination of cholinergic modulation, antioxidant activity, NOS-mediated nitrosative stress reduction, and suppression of arachidonic-acid inflammatory pathways. These findings support C. racemosa as a promising marine-derived multi-target candidate for AD intervention, warranting further mechanistic and in vivo evaluation.

Mangrove forests represent a complex ecosystem inhabiting tropical and subtropical intertidal zones, harboring diverse microbial communities including fungi, actinomycetes, bacteria, cyanobacteria, algae, and protozoa. Among these communities, mangrove-derived fungi, as the second-largest ecological group of marine fungi, not only play essential roles in establishing and sustaining this biosphere but also serve as an important source of structurally unique and biologically active secondary metabolites. This review systematically summarizes research progress on metabolites isolated from mangrove-derived fungi and their associated bioactivities over the recent five years (2020-2025). Emphasis is placed on 457 metabolites documented in 97 selected publications, with a focus on the biological activities and distinctive chemical diversity of these secondary metabolites. This review provides an important reference for the research status of secondary metabolites isolated from mangrove-derived fungi and the lead compounds worthy of further development, and reveals that mangrove-derived fungi have important medicinal values and are worthy of further development.

Airborne particulate matter (PM) triggers oxidative stress and inflammation in pulmonary tissues, contributing to chronic respiratory diseases. This study evaluated the antioxidant and anti-inflammatory effects of a combined extract of Haematococcus pluvialis (H. pluvialis) and walnut shell (HW extract) and its protective efficacy against PM_2.5-induced pulmonary inflammation. Extracts mixed at different ratios (10:0-0:10, w/w) were tested using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, cell-based assays, HPLC quantification, molecular docking, and a PM_2.5-induced pulmonary inflammation mouse model. The optimized 6:4 mixture showed the strongest antioxidant activity (RC₅₀ = 0.61 ± 0.14 μg/mL) and significantly reduced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression without cytotoxicity. HPLC confirmed the presence of astaxanthin (1.714 μg/mg) and quercetin (0.722 μg/mg). Docking simulations indicated strong COX-2 binding affinities (-9.501 and -8.753 kcal/mol) through hydrogen bonding and hydrophobic interactions. In vivo, HW extract reduced leukocyte infiltration, serum IL-6 levels, and pulmonary expression of COX-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) while improving alveolar structure. These results suggest that HW extract exerts synergistic antioxidant and anti-inflammatory actions via dual-site COX-2 modulation, providing a promising natural therapeutic approach for mitigating PM_2.5-induced respiratory inflammation.

Alzheimer's disease (AD) is a common neurodegenerative disorder with limited effective treatments. Cod skin collagen peptides (CSCPs) have neuroprotective potential for AD but face poor bioavailability-due to gastrointestinal enzyme cleavage and hepatic first-pass metabolism-prompting this study to develop a nanodelivery system to enhance CSCPs' efficacy. Trimethyl chitosan (TMC)-based CSCP-loaded nanoparticles (CSCPs-NPs) were synthesized via ionic gelation, characterized for physicochemical properties, and tested in a D-galactose-induced AD mouse model (six groups: normal control, model, CSCPs low/high dose, blank NPs, CSCPs-NPs) using behavioral tests, histopathology, immunohistochemistry, and ELISA. CSCPs-NPs had a hydrodynamic diameter of 93.25 ± 21.52 nm, polydispersity index of 0.18 ± 0.13, 61.17% encapsulation efficiency, and sustained 24 h release. In AD mice, CSCPs-NPs significantly improved cognitive function and motor coordination, reduced hippocampal atrophy, preserved neurons, and mitigated oxidative stress, neuroinflammation, and apoptosis (upregulated Bcl-2, downregulated Bax)-effects matching high-dose free CSCPs. This TMC-based nanoformulation enhances CSCPs' bioavailability and provides a promising strategy for AD intervention.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder requiring safer and more effective therapeutic alternatives. This study investigates a novel fucoxanthin derivative isolated from the marine brown alga Chnoospora minima using a comprehensive in silico approach. Molecular docking revealed that the derivative exhibited higher binding affinities toward α-amylase (-9.4 kcal/mol) and α-glucosidase (-8.0 kcal/mol) compared to the reference drug acarbose (-8.5 and -7.4 kcal/mol, respectively). Pharmacokinetic analysis predicted good intestinal absorption and P-gp inhibition (0.894) and moderate plasma clearance (7.864 mL/min/kg), while toxicity predictions classified it in toxicity class 3, with no respiratory or ocular toxicity. Drug-likeness evaluation showed only one Lipinski and one Veber rule violation, common for natural products. Molecular dynamics simulations conducted for 100 ns using NAMD 3.0 confirmed stable protein-ligand complexes with average RMSD values of ~1.3 Å and ~1.8 Å for α-amylase and α-glucosidase, respectively, and consistent hydrogen bonding profiles. Structural analysis identified a substitution of the allene bond with an unsaturated ketone at the C8' position as a key contributor to enhanced enzyme interaction. The findings suggest that this fucoxanthin derivative is a promising natural candidate for T2DM therapy and warrants further investigation through lab experiments (in vitro and in vivo).

Astaxanthin is a high-value ketocarotenoid antioxidant, but its industrial production from Haematococcus pluvialis is constrained by multi-stage cultivation and a rigid cell wall that hinders downstream extraction. The marine diatom Phaeodactylum tricornutum, which lacks these limitations, represents a promising alternative chassis because it grows fast, lacks a recalcitrant wall, and supports efficient pigment accumulation. This study establishes a functional ketocarotenoid biosynthetic branch in P. tricornutum through rational metabolic engineering. To address challenges in protein targeting posed by the host's complex plastid architecture, we performed heterologous expression of the Chlamydomonas reinhardtii β-carotene ketolase (CrBKT), fused at its N-terminus to bipartite transit peptides derived from two endogenous proteins. Western blotting and UPLC-MS/MS analysis confirmed that only the transit peptide fused constructs produced stable protein and functional activity, whereas the native CrBKT failed. The rationally engineered strain successfully accumulated ~45 µg/g DCW of canthaxanthin and ~15 µg/g DCW of astaxanthin. Metabolomic profiling revealed a 50% reduction in fucoxanthin, indicating a substantial redirection of metabolic flux from the native pathway toward the engineered ketocarotenoid branch. This work establishes P. tricornutum as a viable platform for ketocarotenoid production and highlights the critical role of evolution-aware plastid targeting in heterologous pathway reconstruction within complex algal systems.