Marine Drugs最新文献

The microwave-aided racemic synthesis of six 5-hydroxy-5-vinyl-2-cyclopentenone-type natural products was achieved. A key reaction involving the construction of the α-keto vinyl carbinol function was realized by applying a Mislow-Evans rearrangement of an allylic sulfoxide, which was prepared by conjugate addition of cyclopentane-1,3-dione-derived enolate to alkynyl sulfoxide to afford 5-hydroxy-3-methoxy-5-vinyl-2-cyclopentenone (1). From the common intermediate 1, five other congeneric natural products were synthesized.

In this study, we report the isolation of the known compound 6-isoprenylindole-3-carboxylic acid (SJ196), a prenylated indole derivative, from a marine Streptomyces sp., APA053, and its potent anti-melanogenic activity. SJ196 showed ABTS and DPPH radical scavenging activities and cellular antioxidant activities, significantly suppressing cytoplasmic and mitochondrial reactive oxygen species (ROS) in B16F10 murine melanoma cells. Furthermore, SJ196 reduced both intracellular and extracellular melanin content without cytotoxicity. These effects coincided with suppression of intracellular signal transduction for melanogenesis, significantly reducing phosphorylation of ERK, JNK, and p38 MAPK, and attenuating the expression of MITF and melanogenic enzymes (TYR, TRP-1, and TRP-2). Importantly, in a three-dimensional human skin model (MelanoDerm™), SJ196 exhibited a skin-lightening effect, as evidenced by dose-dependent increases in skin brightness and histological confirmation. Collectively, we demonstrated that SJ196 is a potent anti-melanogenic marine compound that acts through antioxidant activity and MAPK-MITF pathway suppression, suggesting its therapeutic potential for the treatment of age-related hyperpigmentation disorders.

Jellyfish, as high-biomass marine resources, frequently exhibit explosive proliferation in coastal waters and possess both nutritional functional factors and potential medicinal value. This study investigated the enzymatic hydrolysis of two jellyfish species, Rhopilema hispidum (R. hispidum) and Nemopilema nomurai (N. nomurai), using Alcalase, Flavourzyme, and Protamex, with a specific focus on the molecular weight distribution and antioxidant activity. The optimal hydrolysis conditions were systematically determined via single-factor experiments followed by orthogonal test optimization. The Flavourzyme hydrolysates had the highest proportion of low-molecular-weight peptides (<3 kDa) and exhibited the most potent antioxidant activity, while Protamex hydrolysates had more high-molecular-weight peptides (>3 kDa, >40%) with comparatively weaker antioxidant activity. R. hispidum hydrolysates exhibited stronger DPPH• and O₂•^- scavenging activities and contained a higher proportion of low-molecular-weight peptides (<3 kDa), whereas N. nomurai hydrolysates showed a higher degree of hydrolysis, and its hydrolysates demonstrated superior •OH scavenging activity. Chromatographic analysis confirmed low-molecular-weight peptides positively correlated with antioxidant potential. This study highlights molecular weight distribution, together with enzyme type, as a pivotal determinant of the antioxidant activity of jellyfish hydrolysates, providing insights for antioxidant peptide development.

Advances in neuroscience, immunology, and neuroimmunology have revealed that the nervous and immune systems form a bidirectional integrated network, ranging from regulating inflammation to directing stress responses, pivotal for the maintenance of the brain-body physiology. Like peripheral inflammation, neuroinflammation is a conserved process aimed at activating innate/adaptive immune and non-immune cells to effectively deal with bacteria, viruses, toxins, and injuries, and eventually at removing the microbial pathogens and supporting tissue repair and recovery. A failure of this process or the permanent release of pro-inflammatory mediators causes a condition called "chronic low-grade neuroinflammation" resulting in tissue damage and an increased risk of developing neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Marine-derived bioactive components are able to modulate lipid and glucose metabolism as well as inflammation and oxidative stress. In this review, we describe the neuroinflammatory process and its involvement in the pathogenesis and progression of AD, PD, MS, and ALS. Then, we discuss the potential therapeutic efficacy of select marine-derived bioactive components.

Wound healing is a complex process involving coordinated actions of multiple cell types. Therefore, when developing therapeutics to promote wound healing, it is essential to consider the synergistic contributions of various cells at different stages of the healing process. In this study, we evaluated the potential of different extracts of Botryocladia leptopoda as wound-healing agents by examining their effects on antioxidant activity, cytotoxicity, cell migration, anti-inflammatory properties, and expressions of specific biomarkers associated with wound healing. Results indicated that the ethanol extract (FE) and hexane extract (HE) exhibited the highest DPPH radical scavenging activity, reaching up to 94%. The alkaline extract (AE) showed the strongest antioxidant ability in the FICA assay, with a maximum of 99%. In addition, the FE and AE provided anti-inflammatory actions that inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-6 in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Further analyses suggested that the FE and AE enhanced cell proliferation (210% and 112%) and migration (442.2% and 535.6%) and regulated wound healing-related genes, including matrix metalloproteinase 2, MMP9, and tissue inhibitor of metalloproteinase 2 (TIMP2) to avoid scar formation and accelerate wound healing. Lastly, the identification of potential compounds within the extract using the UHPLC system further supports its prospective medical applications. Taken together, these findings indicated that the FE and AE from B. leptopoda exhibited remarkable in vitro wound-healing properties, highlighting their potential for applications in pharmaceutical industries and health food development.

Background: Ultraviolet B (UVB) radiation induces oxidative stress, inflammation, and collagen degradation in skin, leading to photodamage. Ergosterol (ERG)-a sterol widely distributed in fungi and algae, including numerous marine species-possesses antioxidant and anti-inflammatory activities, but its photoprotective mechanisms remain unclear.

Methods: Using integrated in vitro (UVB-irradiated human keratinocytes) and in vivo (topical ERG in a murine UVB model) approaches, combined with transcriptomic and network pharmacology analyses, we evaluated ERG's effects on oxidative stress, inflammation, and extracellular matrix integrity.

Results: ERG treatment preserved keratinocyte viability, reduced reactive oxygen species, and suppressed pro-inflammatory mediators after UVB exposure. In mice, topical ERG significantly attenuated epidermal hyperplasia, maintained tight-junction integrity, and inhibited collagen matrix degradation. Mechanistically, ERG exerted dual inhibition of the nuclear factor kappa B (NF-κB) pathway, which mediates inflammation, and the mitogen-activated protein kinase (MAPK) pathway, which regulates collagen degradation.

Conclusions: These findings identify ERG as a marine-derived sterol with potent photoprotective activity that simultaneously targets oxidative stress, inflammation, and extracellular matrix damage, highlighting its promise as a natural compound for dermatological applications and aligning with ongoing efforts to explore marine-derived agents against skin oxidative stress and inflammation.

Microalgae are used as dietary supplements for humans and animals, due to their excellent nutritional profile. This research aims to characterize Spirugrass^®, a co-product obtained after the extraction of phycocyanin from Limnospira platensis, and to evaluate whether a stabilization treatment involving high-pressure processing (HPP) affects its proteomic profile. The research also aims to evaluate the possible use of Spirugrass^® as feed integration for honeybee health. Proteins were extracted and fractionated using size exclusion chromatography (SEC) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The iron content was measured using atomic absorption spectrometry (AAS). Samples of Spirugrass^® were subjected to HPP at 600 MPa for five minutes and the effect on the integrity of the protein profile was analyzed. Finally, nine groups of 30 newly emerged honeybees were supplemented with Spirugrass^® in a controlled laboratory experiment. SDS-PAGE and SEC enabled the assessment of the quality and integrity of the Spirugrass^® proteome, which contains 80% of the proteins found in the algal biomass, including phycocyanin. The phycocyanin purity indices were 2.07 ± 0.14 and 0.72 ± 0.13 for the L. platensis and Spirugrass^® extracts, respectively. Spirugrass^® maintains a consistent iron content of 261 ± 15 μg/g dry weight, equivalent to 74% of the iron present in the algal biomass. In both L. platensis and Spirugrass^®, iron was predominantly bound to high-molecular-mass proteins, including phycocyanin. Following HPP treatment, differences in the protein profiles were observed, which suggests partial protein degradation. Preliminary data obtained with honeybees are encouraging, as no mortality or adverse effects were observed and Spirugrass^® can be considered a promising candidate as feed supplement. Overall, the presence of consistent levels of soluble proteins, as well as protein-bound iron, suggests that Spirugrass^® could be used in animal nutrition.

The social amoeba Dictyostelium discoideum is a versatile biological model widely used in drug discovery and studying cellular stress responses. However, its application for cytotoxicity evaluation of natural products, particularly algal-derived compounds, remains underutilized. In this study, we developed a high-throughput developmental assay in D. discoideum to analyze the cytotoxicity of acetone and methanol extracts from the Peruvian seaweed Glossophora kunthii. Our results showed that the acetone extract caused a transient delay in the social development of the amoeba. In contrast, the methanol extract exhibited no significant effects, even at high extract concentrations. UHPLC/Orbitrap/ESI/MS/MS analysis tentatively identified ten major compounds, including pachydictyol A and dictyotriol A diacetate. The presence of diterpenes, such as dictyotadiol and pachydictyol A, previously reported to exhibit moderate cytotoxic activity, likely explains the developmental delay observed with the acetone extract. This study highlights the utility of D. discoideum as a scalable cytotoxicity screening platform within algal pharmacognosy, facilitating the early identification of non-toxic marine natural products suitable for further biomedical and biotechnological development.

Although marine sponges display strikingly diverse colors, the molecular basis of this color diversity remains largely unknown. Recently, the blue coloration of Haliclona sp. was attributed to a water-soluble carotenoprotein that binds orange astaxanthin (AXT) and mytiloxanthin (MXT) and belongs to the ependymin superfamily. Here, we investigated the coloration mechanism of a purple sponge, Haliclona sp. The purified purple protein was identified as a secreted glycoprotein, representing the second example of a color protein belonging to the ependymin superfamily. The blue and purple proteins were accordingly designated carotenoependymin (Cep)-Blue1 and Cep-Purple1. Cep-Blue1 binds orange AXT and MXT in a 1:1 ratio, whereas Cep-Purple1 binds only AXT, producing a smaller red shift than Cep-Blue1 in the 550-750 nm range. In vitro reconstitution of carotenoid-free apoproteins with their native carotenoids reproduced the original spectra. When the carotenoids bound to Cep-Blue1 and Cep-Purple1 were exchanged and reconstituted in vitro, Cep-Blue1 reconstituted with AXT exhibited a purplish-blue color, whereas Cep-Purple1 reconstituted with an equimolar mixture of AXT and MXT showed a preference for AXT and displayed an incomplete red shift. These results suggest that the subtle color variations among Haliclona species are determined by both species-specific carotenoid composition and the structural features of carotenoependymin proteins.

Fucoxanthin (Fx), a marine xanthophyll carotenoid, has attracted considerable scientific attention due to its wide-ranging biological activities, including antioxidant, anti-inflammatory, anti-obesity, and anticancer effects. Despite its substantial therapeutic potential, the clinical application of Fx and its derivatives remains constrained by their structural complexity, low chemical stability, and limited bioavailability. This review offers a thorough and up-to-date overview of Fx, encompassing its primary natural sources, the metabolic biotransformation to fucoxanthinol (FxOH) and amarouciaxanthin A-metabolites whose bioactive properties significantly contribute to the observed in vivo effects-and the molecular mechanisms underlying the biological activities of Fx and its metabolites, with emphasis on their modulation of key intracellular signalling pathways involved in inflammation, lipid metabolism, and cell proliferation. Furthermore, it explores how targeted structural modifications may enhance the pharmacokinetic profiles and expand the therapeutic potential of Fx-based compounds, while highlighting promising strategies for their optimisation. By integrating insights from pharmacology, biochemistry, and synthetic chemistry, this work aims to guide future efforts in the rational design of marine-derived bioactive agents and underscores the value of marine biodiversity in therapeutic innovation.