Marine Drugs

16 pages, 2006 KB

Open AccessArticle

Starfish-Derived Extracts Enhance Mitophagy and Suppress Senescence-Associated Markers in Human Dermal Fibroblasts

by Hyun Jung Lee, Junhee Kim, Bada Won, Dong Hun Lee and Ok Sarah Shin

Mar. Drugs 2025, 23(11), 418; https://doi.org/10.3390/md23110418 (registering DOI) - 27 Oct 2025

While the starfish species Asterias pectinifera (Ap) and Asterias amurensis (Aa) are considered ecological threats to marine environments and the fishing industry, recent studies have identified them as rich sources of highly water-soluble, non-toxic collagen peptides. Mitochondrial dysfunction is [...] Read more.

While the starfish species Asterias pectinifera (Ap) and Asterias amurensis (Aa) are considered ecological threats to marine environments and the fishing industry, recent studies have identified them as rich sources of highly water-soluble, non-toxic collagen peptides. Mitochondrial dysfunction is a key driver of cellular senescence and skin aging, yet the therapeutic potential of marine-derived extracts in modulating mitophagy remains largely unexplored. In this study, we investigated whether starfish-derived extracts could mitigate senescence-associated phenotypes in human dermal fibroblasts (HDFs) through the modulation of mitophagy. Treatment with Ap- or Aa-derived extracts led to reduced senescence-associated β-galactosidase (SA-β-gal) activity, decreased expression of matrix metalloproteinase-1 (MMP-1), and suppression of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-8 (IL-8). Ap- or Aa-derived extracts significantly increased mitophagy in HDFs stably expressing mitochondrial-targeted Keima (HDF-mtKeima), while knockdown of PINK1, the essential regulator of mitophagy, abolished the mitophagy-inducing effects of Ap- or Aa-treatment, indicating that Ap- or Aa-derived extracts activate PINK1/Parkin-dependent mitophagy pathways. Importantly, PINK1 knockdown reversed starfish-induced suppression of MMP-1 and p21, demonstrating its crucial role in regulating senescence-associated gene expression. Additionally, Ap or Aa treatments significantly reduced reactive oxygen species (ROS) accumulation, improved mitochondrial function, and enhanced both basal and maximal respiratory capacity in senescent HDFs. These findings highlight that extracts derived from starfish promote mitophagy through PINK1-dependent mechanisms, exhibiting significant anti-senescence effects in HDFs. This suggests their potential application in the development of novel cosmeceuticals with skin-protective and rejuvenating properties. Full article

(This article belongs to the Special Issue Marine Natural Products with Skin Health-Promoting Properties)

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22 pages, 9751 KB

Open AccessArticle

Metabolomic Insights into the Phytochemical Profiles and Seasonal Shifts of Fucus serratus and F. vesiculosus Harvested in Danish Coastal Waters (Aarhus Bay)—An Untargeted High-Resolution Mass-Spectrometry Approach

by Mihai Victor Curtasu, Jørgen Ulrik Graudal Levinsen, Annette Bruhn, Mette Olaf Nielsen and Natalja P. Nørskov

Mar. Drugs 2025, 23(11), 417; https://doi.org/10.3390/md23110417 (registering DOI) - 26 Oct 2025

Abstract

This study investigated the year-round metabolomic variation in Fucus serratus (FS) and F. vesiculosus (FV) collected monthly from Danish coastal water around Aarhus Bay. Untargeted high-resolution liquid chromatography–mass spectrometry profiling (LC-HRMS), combined with multivariate data analysis and temporal clustering analysis, revealed that species [...] Read more.

This study investigated the year-round metabolomic variation in Fucus serratus (FS) and F. vesiculosus (FV) collected monthly from Danish coastal water around Aarhus Bay. Untargeted high-resolution liquid chromatography–mass spectrometry profiling (LC-HRMS), combined with multivariate data analysis and temporal clustering analysis, revealed that species identity was the primary driver of metabolic separation, followed by seasonal variation. FS showed higher levels of hydrolyzable tannins, flavonoid derivatives, aromatic amino acids, and glutamine-rich peptides, whereas FV was enriched in complex phlorotannins, tricarboxylic acid cycle intermediates, and carnitine derivatives. Temporal analysis identified recurring seasonal patterns across both species, including spring increases in amino acids, purine metabolites, and osmolytes; mid-summer peaks in mannitol and sulfated derivatives; and late-autumn elevations in phenolic compounds and betaine-type osmolytes. Despite apparent interspecific differences, several metabolite groups exhibited similar seasonal dynamics, suggesting shared physiological strategies associated with growth activation in spring, metabolic adjustment during summer to possible increased grazing pressure, and nutrient reallocation prior to winter. These findings provide a comprehensive, high-resolution view of seasonal metabolomic patterns in Fucus spp., offering new insights into their biochemical ecology and supporting the targeted utilization of these species for applications requiring specific metabolite profiles. Finally, this study contributes to the creation or expansion of metabolomic libraries for HRMS specific to Fucus seaweeds. Full article

(This article belongs to the Special Issue Omics Approaches in Marine Compound Discovery)

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10 pages, 1034 KB

Open AccessArticle

Montagnulans A–D with Anti-Osteoclastogenic Activity from the Marine Fungus Montagnula sp. GXIMD 02514

by Miaoping Lin, Humu Lu, Jiaxi Wang, Huangxue Qin, Xinya Xu, Chenghai Gao, Yonghong Liu, Yanhui Tan and Xiaowei Luo

Mar. Drugs 2025, 23(11), 416; https://doi.org/10.3390/md23110416 (registering DOI) - 25 Oct 2025

Abstract

Four novel tetramic acid compounds, montagnulans A–D (1–4), were obtained from the Beibu Gulf coral-associated fungus Montagnula sp. GXIMD 02514. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations were accomplished by ECD calculations. [...] Read more.

Four novel tetramic acid compounds, montagnulans A–D (1–4), were obtained from the Beibu Gulf coral-associated fungus Montagnula sp. GXIMD 02514. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations were accomplished by ECD calculations. Structurally, compounds 1–4 were rare leucine-derived tetramic acids bearing an ethyl (1–3) or hexylenic alcohol (4) side chain and a pyranone ring at C-3 of the 2,4-pyrrolidinedione core. Compound 1 exhibited inhibition of lipopolysaccharide (LPS)-induced NF-κB in RAW 264.7 macrophages at 20 μM, which further inhibited RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophages cells (BMMs). This is the first report of osteoclastogenesis inhibitions for tetramic acids, which sheds light on their development as potential osteoclast differentiation inhibitors. Full article

(This article belongs to the Special Issue Selected Papers from the 2025 Symposium on Marine Microbiology in China)

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30 pages, 2794 KB

Open AccessReview

Therapeutic Potential of Neopyropia yezoensis: An Updated Review

by Anshul Sharma, Na Young Yoon and Hae-Jeung Lee

Mar. Drugs 2025, 23(11), 415; https://doi.org/10.3390/md23110415 - 23 Oct 2025

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Abstract

Neopyropia (N.) yezoensis is a widely cultivated red alga in East Asia and valued worldwide for its rich bioactive constituents recognized for their health benefits, including polsaccharides, porphyrans, pigments, phenolic compounds, phycobiliproteins, polyunsaturated fatty acids, myosporin-like amino acids, and both synthetic [...] Read more.

Neopyropia (N.) yezoensis is a widely cultivated red alga in East Asia and valued worldwide for its rich bioactive constituents recognized for their health benefits, including polsaccharides, porphyrans, pigments, phenolic compounds, phycobiliproteins, polyunsaturated fatty acids, myosporin-like amino acids, and both synthetic and recombinant peptides. This review summarizes the current knowledge regarding the therapeutic potential of N. yezoensis extracts and their bioactive compounds. Based on in vitro, ex vitro, and in vivo experimental data (including those on Drosophila melanogaster larvae), this review comprehensively discusses its antioxidant, anti-inflammatory, neuroprotective, anti-atopic dermatitis, anti-colitis, anticancer, anti-aging, anti-atrophy, metabolic health-promoting effects, improving renal health, proliferating, anti-osteoarthritic, anti-allergic, antibacterial, and antivirus activities. The prebiotic effect of N. yezoensis porphyran through modulation of the gut microbiota was also investigated. Studies have indicated that protein hydrolysates and peptides derived from N. yezoensis with low molecular weights and aromatic and/or hydrophobic amino acids contribute significantly to these diverse bioactivities. Although N. yezoensis has shown promising bioactivity in preclinical models, validated clinical data in humans are currently lacking. Future research should prioritize the design and implementation of well-controlled human clinical trials to fully explore their therapeutic potential. Full article

(This article belongs to the Special Issue Bioactive Specialized Metabolites from Marine Plants)

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16 pages, 4650 KB

Open AccessArticle

5Z-7-Oxozeanol Isolated from the Fungus Curvularia sp. MDCW-1060 Inhibits the Proliferation of MDA-MB-231 Cells via the PI3K-Akt and MAPK Pathways

by Hong Zhang, Jianjian Wang, Chang Xu, Kai Liu, Jufang Xie, Zhoucheng He, Yonghong Liu, Cong Wang and Xinjian Qu

Mar. Drugs 2025, 23(11), 414; https://doi.org/10.3390/md23110414 - 23 Oct 2025

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Abstract

The discovery of novel marine natural products and their sustainable application continue to be vital focuses in marine biological research. The aim of this study is to investigate the inhibitory effect of the compound 5Z-7-Oxozeaenol isolated from the fungus Curvularia sp. MDCW-1060 on [...] Read more.

The discovery of novel marine natural products and their sustainable application continue to be vital focuses in marine biological research. The aim of this study is to investigate the inhibitory effect of the compound 5Z-7-Oxozeaenol isolated from the fungus Curvularia sp. MDCW-1060 on the proliferation of MDA-MB-231 cells and its molecular mechanism. A series of functional assays, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, Transwell migration, and colony formation, were employed to evaluate the effects of 5Z-7-Oxozeaenol on cellular viability, apoptosis, migration, and clonogenicity. The RNA sequencing (RNA-seq) coupled with bioinformatic analysis was conducted to identify affected differentiated gene expression and signaling pathways. The molecular docking was performed to predict potential protein targets, and Western blot was used to validate expression and phosphorylation levels of key signaling molecules. The results demonstrated that 5Z-7-Oxozeaenol significantly suppressed proliferation and migration while promoting apoptosis in MDA-MB-231 cells. The transcriptomic analysis indicated enrichment in pathways related to cancer, cytokine–cytokine receptor interaction, MAPK and PI3K-Akt signaling, and cell adhesion molecules. The molecular docking suggested a high binding affinity between 5Z-7-Oxozeaenol and PTPRN. While Western blot analysis confirmed the downregulation of phosphorylated FAK, PI3K, Akt, and MAPK, along with reduced cyclin D1 expression. Additionally, 5Z-7-Oxozeaenol upregulated the pro-apoptotic proteins p53 and cleaved caspase-3. In conclusion, 5Z-7-Oxozeaenol exerts potent antitumor effects on MDA-MB-231 cells through multi-pathway inhibition and induction of apoptosis, highlighting its potential as a marine-derived therapeutic candidate for breast cancer treatment. Full article

(This article belongs to the Special Issue Marine Compounds as Inhibitors)

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15 pages, 6179 KB

Open AccessArticle

Identifying a Marine-Derived Small-Molecule Nucleoprotein Inhibitor Against Influenza A Virus

by Zihan Wang, Yang Zhang, Shangjie Xu, Lishan Sun, Hongwei Zhao and Wei Wang

Mar. Drugs 2025, 23(11), 413; https://doi.org/10.3390/md23110413 - 23 Oct 2025

Viewed by 92

Abstract

Influenza A virus (IAV) poses a major threat to global public health, exerting immense pressure on human health and the economy. The IAV nucleoprotein (NP) is an ideal target for antiviral drug development. Through Mini-genome and Surface Plasmon Resonance assays, this study discovered [...] Read more.

Influenza A virus (IAV) poses a major threat to global public health, exerting immense pressure on human health and the economy. The IAV nucleoprotein (NP) is an ideal target for antiviral drug development. Through Mini-genome and Surface Plasmon Resonance assays, this study discovered and verified that mycophenolic acid methyl ester (MAE), a secondary metabolite produced by the marine algal-associated fungus Phaeosphaeria spartinae, can target the viral nucleoprotein to exert anti-IAV activity. Pull-down assays and immunofluorescence have revealed that MAE blocks the nuclear import of viral ribonucleoprotein complexes (vRNP) by interfering with the interaction between NP and IMP-α. It also affects the vRNP assembly process by regulating NP oligomerization and the interaction between NP and PB2. In addition, Sandwich ELISA and Electron Microscopy experiments showed that MAE can also inactivate viral particles to reduce the risk of infection. Comprehensive research results indicate that MAE exerts its effects by inhibiting the viral NP protein, which has laid an important foundation for the development of marine-derived NP-targeted drugs. Full article

(This article belongs to the Special Issue Marine Compounds as Inhibitors)

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26 pages, 3924 KB

Open AccessReview

Seaweed Polysaccharides: A Rational Approach for Food Safety Studies

by João Cotas, Mariana Lourenço, Artur Figueirinha, Ana Valado and Leonel Pereira

Mar. Drugs 2025, 23(11), 412; https://doi.org/10.3390/md23110412 - 22 Oct 2025

Viewed by 511

Abstract

Marine macroalgae (seaweed) are a rich source of bioactive polysaccharides such as agar, carrageenan, and alginate. These three compounds are classified as food additive ingredients, widely used as gelling, thickening, stabilizing, and emulsifying agents in the food, nutraceutical, pharmaceutical, and cosmetic industries. However, [...] Read more.

Marine macroalgae (seaweed) are a rich source of bioactive polysaccharides such as agar, carrageenan, and alginate. These three compounds are classified as food additive ingredients, widely used as gelling, thickening, stabilizing, and emulsifying agents in the food, nutraceutical, pharmaceutical, and cosmetic industries. However, the growing concern for a safer world has sparked renewed interest in their safety evaluation. Unlike synthetic compounds with specified structures, seaweed polysaccharides exhibit substantial structural heterogeneity due to variations in species, habitat, and processing, affecting bioactivity, digestibility, and interactions within the gastrointestinal tract. Although the safety of these compounds is generally accepted, there are still significant gaps in our understanding of their physicochemical behaviour. This highlights the need to develop a standardized digestion model to ensure their safety and evaluate their potential long-term health effects. Most of these compounds are only partially absorbed in the upper gastrointestinal tract, where they are fermented into metabolites with varying health effects. The safety of carrageenan, in particular, remains a subject of debate due to ambiguous results reported by various researchers’ groups. This review highlights the importance of adopting standardized digestion assays, integrated analytical tools, and multidisciplinary approaches. These are crucial for thoroughly evaluating the molecular integrity, metabolism, and biological impact of seaweed polysaccharides, which will ultimately support evidence-based regulatory frameworks and ensure their safe use in human nutrition. This critical analysis focuses on food safety and security, with a methodology that can be applied to other foods or compounds. Full article

(This article belongs to the Section Marine-Derived Ingredients for Drugs, Cosmeceuticals and Nutraceuticals)

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24 pages, 2295 KB

Open AccessArticle

Sea Cucumber (Isostichopus badionotus): Bioactivity and Wound Healing Capacity In Vitro of Small Peptide Isolates from Digests of Whole-Body Wall or Purified Collagen

by Leticia Olivera-Castillo, George Grant, Oscar Medina-Contreras, Honorio Cruz-López, Leydi Carrillo-Cocom, Ariadnna Cruz-Córdova, Frank Segura-Cadiz, Daniel Alejandro Fernández-Velasco, Sergio Rodríguez-Morales, Juan Valerio Cauich-Rodríguez, Rosa Esther Moo-Puc, César Puerto-Castillo, Gabriela de Jesus Moo-Pech, Jonatan Jafet Uuh-Narvaez, Miguel Angel Olvera-Novoa and Rossanna Rodriguez-Canul

Mar. Drugs 2025, 23(11), 411; https://doi.org/10.3390/md23110411 - 22 Oct 2025

Viewed by 527

Abstract

Low-molecular-weight peptides derived from the digestion of body wall proteins in some sea cucumber species have wound-healing and health-promoting properties, but their potency varies widely by species, growth environment, age, and season. For the first time, small peptide (1–3 kDa) fractions have been [...] Read more.

Low-molecular-weight peptides derived from the digestion of body wall proteins in some sea cucumber species have wound-healing and health-promoting properties, but their potency varies widely by species, growth environment, age, and season. For the first time, small peptide (1–3 kDa) fractions have been isolated from the whole-body wall of the sea cucumber Isostichopus badionotus and its constituent collagen and tested for wound healing capacity in vitro. Ultrafiltered digests (1–3 kDa) of the pure collagen, as well as 1–3 kDa digests of the whole-body wall, had potent antioxidant activities and promoted rapid wound healing in a keratinocyte scratch wound assay. Gene expression studies suggested that the wound-healing actions of the individual collagen and body wall 1–3 kDa fractions differed significantly. Low-molecular-weight peptides derived from I. badionotus collagen did promote wound healing in vitro; however, their efficacy may have been modulated by additional factors produced during body wall or collagen digestion. These findings need to be confirmed in vivo. Full article

(This article belongs to the Special Issue Collagen and Chitin from Marine Resources and Their Interdisciplinary Applications—2nd Edition)

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Mar. Drugs, Volume 23, Issue 11 (November 2025) – 8 articles

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