You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.

Search for Articles:

Title / Keyword

Author / Affiliation / Email

Journal

Article Type

Advanced Search

Section

Special Issue

Volume

Issue

Number

Page

Logical OperatorOperator

Search Text

Search Type

Journal Description

Marine Drugs

Marine Drugs is the leading, peer-reviewed, open access journal on the research, development, and production of biologically and therapeutically active compounds from the sea. Marine Drugs is published monthly online by MDPI. Australia New Zealand Marine Biotechnology Society (ANZMBS) is affiliated with Marine Drugs and its members receive a discount on article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, MarinLit, AGRIS, and other databases.
Journal Rank: JCR - Q1 (Pharmacology and Pharmacy) / CiteScore - Q1 (Pharmacology, Toxicology and Pharmaceutics (miscellaneous))
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.7 days after submission; acceptance to publication is undertaken in 1.9 days (median values for papers published in this journal in the second half of 2024).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.

Impact Factor: 4.9 (2023); 5-Year Impact Factor: 5.2 (2023)

Imprint Information Journal Flyer Open Access ISSN: 1660-3397

Latest Articles

17 pages, 2589 KiB

Open AccessArticle

Rhamnan Sulfate from the Seaweed Monostroma nitidum May Improve Cognitive Impairment Caused by Hyperglycemia

by Takaichi Miwa, Masaya Sato, Ning Ma, Keiichi Hiramoto, Masahiro Terasawa and Koji Suzuki

Mar. Drugs 2025, 23(6), 250; https://doi.org/10.3390/md23060250 - 12 Jun 2025

Rhamnan sulfate (RS), extracted from the seaweed Monostroma nitidum, suppresses vascular endothelial inflammation and arteriosclerosis, decreases blood glucose levels, and improves blood lipid metabolism and the intestinal environment. We examined whether RS improves hyperglycemia-induced cognitive decline in a hyperglycemic mouse model pretreated [...] Read more.

Rhamnan sulfate (RS), extracted from the seaweed Monostroma nitidum, suppresses vascular endothelial inflammation and arteriosclerosis, decreases blood glucose levels, and improves blood lipid metabolism and the intestinal environment. We examined whether RS improves hyperglycemia-induced cognitive decline in a hyperglycemic mouse model pretreated with nicotinamide and streptozotocin and then orally administered a high-fat diet and maltodextrin (MD) for 4 months. RS was administered in an MD solution at doses of 75, 225, and 750 mg/kg of mouse body weight. Administration of RS to hyperglycemic mice significantly reduced blood glucose levels and tended to improve memory function in behavioral pharmacological tests using spontaneous locomotor activity, rotarod test, and eight-way-maze test, although the results were not significant. Brain histopathological analysis showed that RS significantly reduced atrophy of neuronal layers in each region of the hippocampus compared with untreated hyperglycemic controls. RS also significantly suppressed TNF-α expression and microglial activation in the brain. These results suggest that RS intake suppresses inflammation in the brain and alleviates the cognitive impairment associated with hyperglycemic diabetes. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 5th Edition)

► Show Figures

Figure 1

18 pages, 1214 KiB

Open AccessArticle

Microwave Pretreatment-Induced Significant Nutrient and Metabolite Changes in Sea Cucumber Apostichopus japonicus

by Dairong Song, Fang Liu, Airong Jia, Xue Liu, Tingting Cui, Hui Zhang and Miansong Zhang

Mar. Drugs 2025, 23(6), 249; https://doi.org/10.3390/md23060249 - 11 Jun 2025

The body wall of sea cucumbers is rich in nutrients and small-molecule metabolites; however, traditional hot water pretreatment often leads to nutrient loss. To optimise processing techniques, this study compared the effects of microwave pretreatment and conventional hot water pretreatment on nutrient retention [...] Read more.

The body wall of sea cucumbers is rich in nutrients and small-molecule metabolites; however, traditional hot water pretreatment often leads to nutrient loss. To optimise processing techniques, this study compared the effects of microwave pretreatment and conventional hot water pretreatment on nutrient retention and metabolite profiles. Untreated sea cucumber body wall samples served as controls. The samples were subjected to microwave pretreatment (4 W/g, 12 min) or hot water pretreatment (100 °C, 10 min). Nutrient retention rates and metabolite variations were systematically analysed. Microwave pretreatment demonstrated superior retention of protein (96%), crude fat (92%), total sugar (55%), and saponins (40%). It also promotes the accumulation of small-molecule metabolites, including spermidine, tagatose, and melatonin. Notably, the lysine and methionine retention rates were enhanced by 10-fold and 12-fold, respectively, while the vitamin A, vitamin B3, and melatonin retention increased by 2.4-fold, 2-fold, and 3-fold, significantly outperforming traditional pretreatment. These findings highlight the potential of microwave pretreatment as an efficient alternative to conventional methods for preserving the nutritional and functional components of sea cucumbers. Full article

(This article belongs to the Special Issue New Methods in Extraction and Isolation of Marine Natural Products)

► Show Figures

Figure 1

17 pages, 2393 KiB

Open AccessArticle

Evaluation of the Immunostimulatory Effect of Ulvan Polysaccharide on Human Macrophages: Use as a Potential Vaccine Adjuvant

by Valeska Guevara-Torrejón, Paola Chandía Parra, Carolina Campos-Estrada and Waleska E. Vera Quezada

Mar. Drugs 2025, 23(6), 248; https://doi.org/10.3390/md23060248 - 11 Jun 2025

The ulvans are sulfated heteropolysaccharides that can stimulate the immune response in vitro. Using a human cell model, this study aimed to characterize and evaluate the immunostimulatory properties of crude ulvans extracted from Ulva spp., collected in Algarrobo, Chile. The crude ulvans, characterized [...] Read more.

The ulvans are sulfated heteropolysaccharides that can stimulate the immune response in vitro. Using a human cell model, this study aimed to characterize and evaluate the immunostimulatory properties of crude ulvans extracted from Ulva spp., collected in Algarrobo, Chile. The crude ulvans, characterized by spectrophotometric methods, are composed of 47.6% total sugars, 14.3% uronic acids, and 8.9% sulfates, with an average molecular weight of 40.000 kDa. The FTIR spectrum showed bands related to uronic acids, rhamnose, and sulfate groups. GCMS analysis confirmed the presence of rhamnose, xylose, glucose, and galactose, with a predominance of the disaccharides U3s and B3s. HL60 cells differentiated into macrophages were cultured with three concentrations of crude ulvans (25, 50, and 100 μg/mL), with cell viability remaining above 90% at the lower concentrations. The crude ulvan activated CD86 co-stimulatory molecules and promoted the release of IL-6, IL-10, IL-4, and nitric oxide cytokines. The results suggest that ulvan is non-toxic and can activate inflammatory pathways, making it a potential candidate for studies as a vaccine adjuvant. Full article

(This article belongs to the Special Issue Marine Polysaccharides and Oligosaccharides: Extraction and Biological Activities)

► Show Figures

Graphical abstract

20 pages, 2929 KiB

Open AccessArticle

A Chemoinformatics Investigation of Spectral and Quantum Chemistry Patterns for Discovering New Drug Leads from Natural Products Targeting the PD-1/PD-L1 Immune Checkpoint, with a Particular Focus on Naturally Occurring Marine Products

by Henrique Rabelo, Ayana Tsimiante, Yuri Binev and Florbela Pereira

Mar. Drugs 2025, 23(6), 247; https://doi.org/10.3390/md23060247 - 10 Jun 2025

(1) Background: Although the field of natural product (NP) drug discovery has been extensively developed, there are still several bottlenecks hindering the development of drugs from NPs. The PD-1/PD-L1 immune checkpoint axis plays a crucial role in immune response regulation. Therefore, drugs targeting [...] Read more.

(1) Background: Although the field of natural product (NP) drug discovery has been extensively developed, there are still several bottlenecks hindering the development of drugs from NPs. The PD-1/PD-L1 immune checkpoint axis plays a crucial role in immune response regulation. Therefore, drugs targeting this axis can disrupt the interaction and enable immune cells to continue setting up a response against the cancer cells. (2) Methods: We have explored the immuno-oncological activity of NPs targeting the PD-1/PD-L1 immune checkpoint by estimating the half maximal inhibitory concentration (IC₅₀) through molecular docking scores and predicting it using machine learning (ML) models. The LightGBM (Light Gradient-Boosted Machine), a tree-based ML technique, emerged as the most effective approach and was used for building the quantitative structure–activity relationship (QSAR) classification model. (3) Conclusions: The model incorporating 570 spectral descriptors from NMR SPINUS was selected for the optimization process, and this approach yielded results for the external test set with a sensitivity of 0.74, specificity of 0.81, overall predictive accuracy of 0.78, and Matthews correlation coefficient (MCC) of 0.55. The strategy used here for estimating the IC₅₀ from docking scores and predicting it through ML models appears to be a promising approach for pure compounds. Nevertheless, further optimization is indicated, particularly through the simulation of the spectra of mixtures by combining the spectra of individual compounds. Full article

(This article belongs to the Special Issue Chemoinformatics for Marine Drug Discovery)

► Show Figures

Graphical abstract

15 pages, 3326 KiB

Open AccessArticle

Structural and Functional Insights into a Novel Aspergillus ochraceus Polysaccharide from the Weddell Sea: Implications for Melanoma Immunotherapy In Vitro

by Jiale Hao, Kouame kra Wilfred Armel, Pengcheng Gao, Jinglei Wang, Weibin Zhang, Kexin Du, Qi Li, Huishu Gao, Guangli Yu and Guoyun Li

Mar. Drugs 2025, 23(6), 246; https://doi.org/10.3390/md23060246 - 10 Jun 2025

Immunotherapy is a transformative strategy in oncology, yet the development of novel immunomodulatory agents remains essential. This study explores the anti-tumor potential of a structurally unique polysaccharide isolated from an Aspergillus ochraceus (AOP), sourced from the Antarctic Weddell Sea. Using alkaline-assisted extraction and [...] Read more.

Immunotherapy is a transformative strategy in oncology, yet the development of novel immunomodulatory agents remains essential. This study explores the anti-tumor potential of a structurally unique polysaccharide isolated from an Aspergillus ochraceus (AOP), sourced from the Antarctic Weddell Sea. Using alkaline-assisted extraction and chromatographic purification, we obtained a homogeneous polysaccharide predominantly composed of galactose and mannose, with an average molecular weight of 39.67 kDa. The structure was characterized by an integrated nuclear magnetic resonance spectroscopy and mass spectrometry analysis, revealing that the AOP is composed of β (1→5)-linked galactofuranose units, with a minor substitution by α-D-mannopyranose residues via (1→2) glycosidic bonds at the C2 of the galactofuranose. Functional assays, including CCK8 and wound-healing tests, demonstrated that this polysaccharide, referred to as AOP, inhibited melanoma cell proliferation and migration in a dose-dependent manner. Additionally, the AOP activated RAW264.7 and bone marrow-derived macrophage (BMDM) cells without exhibiting significant cytotoxicity, leading to the release of inflammatory factors such as TNF-α, IL-1β, and IL-6. Mechanistically, the AOP was found to upregulate the expression of CD86 and IFN-γ, while downregulating genes like IL-4 and Arg1. These findings position the AOP as the first documented Antarctic fungal polysaccharide with macrophage-reprogramming capabilities against melanoma, offering novel molecular insights for marine-derived immunotherapeutics. Full article

(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 2nd Edition)

► Show Figures

Graphical abstract

18 pages, 1844 KiB

Open AccessArticle

Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization

by Johanna Maria Hölken, Katja Friedrich, Russel Kerr and Nicole Elisabeth Teusch

Mar. Drugs 2025, 23(6), 245; https://doi.org/10.3390/md23060245 - 10 Jun 2025

This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO₄)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO₄-induced upregulation of key activation surface markers, cluster [...] Read more.

This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO₄)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO₄-induced upregulation of key activation surface markers, cluster of differentiation (CD)54 (~1.2-fold), and CD86 (~1.6-fold). Additionally, PsA-D inhibited the NiSO₄-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by suppressing inhibitor of kappa B alpha (IκBα) degradation. Furthermore, PsA-D suppressed inflammatory responses by inhibiting the NiSO₄-induced secretion of pro-inflammatory cytokines, including interleukin (IL)-8 (~6.8-fold), IL-6 (~2.2-fold), and IL-1β (~5.3-fold). In a full-thickness human skin model incorporating DDC surrogates, topical application of PsA-D effectively attenuated NiSO₄-induced mRNA expression of IL-8 (~2.1-fold), IL-6 (~2.6-fold), and IL-1β (~2.2-fold), along with the key inflammatory mediators cyclooxygenase-2 (COX-2) (~3.5-fold) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) (~2.1-fold). Overall, PsA-D demonstrated comparable efficacy to dexamethasone, a benchmark corticosteroid, providing a promising therapeutic alternative to corticosteroids for the treatment of skin sensitization and allergic contact dermatitis. However, to maximize PsA-D’s therapeutic potential, future studies on optimizing the bioavailability and formulation of PsA-D are required. Full article

(This article belongs to the Special Issue Marine Natural Products with Immunomodulatory Activity)

► Show Figures

Graphical abstract

15 pages, 823 KiB

Open AccessArticle

Research on the Influence of Orthogonal Design Optimized Elicitor Combinations on Fucoxanthin Accumulation in Phaeodactylum tricornutum and Its Expression Regulation

by Han Yang, Yifu Gong, Boyue Liu, Yuru Chen, Huan Qin, Heyu Wang and Hao Liu

Mar. Drugs 2025, 23(6), 244; https://doi.org/10.3390/md23060244 - 9 Jun 2025

Fucoxanthin, a carotenoid with notable pharmaceutical potential, has attracted significant attention due to its efficient accumulation in marine microalgae and the importance of optimizing its induction conditions. In this study, Phaeodactylum tricornutum was employed as a model organism to screen optimal conditions for [...] Read more.

Fucoxanthin, a carotenoid with notable pharmaceutical potential, has attracted significant attention due to its efficient accumulation in marine microalgae and the importance of optimizing its induction conditions. In this study, Phaeodactylum tricornutum was employed as a model organism to screen optimal conditions for fucoxanthin accumulation using a three-factor, four-level orthogonal design. Furthermore, the underlying mechanisms related to photosynthetic physiology and gene regulation were explored. The results revealed that both glycine (Gly) and light intensity significantly enhanced fucoxanthin content (p < 0.05). The optimal condition (Combination C: 0.50 g L⁻¹ Gly, 36 μmol photons·m⁻²·s⁻¹, 12 h light/12 h dark) yielded a fucoxanthin content of 0.87 μg g⁻¹, representing a 35% increase compared to the control. Meanwhile, Combination p (0.50 g L⁻¹ Gly, 36 μmol photons·m⁻²·s⁻¹, 24 h light/0 h dark) significantly improved cell density (5.11 × 10⁶ cells mL⁻¹; +18%) and fucoxanthin yield (4.10 μg L⁻¹; +47%). Analysis of photosynthetic parameters demonstrated that the non-photochemical quenching coefficient (NPQ) was suppressed. Gene expression profiling showed that Combination C upregulated photosynthetic genes (psbA, rbcL, rbcS) by up to 2.36-fold, while Combination P notably upregulated fcpb (7.59-fold), crtiso, and pds. Principal component analysis identified that rbcS and pds are key regulatory genes. These findings demonstrate that Gly, light intensity, and photoperiod synergistically regulate the expression of genes involved in photosynthesis and carotenoid biosynthesis, thereby promoting fucoxanthin accumulation. This work provides valuable insights and a theoretical basis for optimizing fucoxanthin production in support of marine drug development. Full article

(This article belongs to the Special Issue Algal Cultivation for Obtaining High-Value Products, 2nd Edition)

► Show Figures

Figure 1

5 pages, 148 KiB

Open AccessEditorial

Marine Natural Products as Anticancer Agents 3.0

by Celso Alves and Marc Diederich

Mar. Drugs 2025, 23(6), 243; https://doi.org/10.3390/md23060243 - 5 Jun 2025

Cancer represents a major global health challenge[...] Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 3.0)

21 pages, 2879 KiB

Open AccessArticle

Undaria pinnatifida Fucoidan Enhances Gut Microbiome, Butyrate Production, and Exerts Anti-Inflammatory Effects in an In Vitro Short-Term SHIME^® Coupled to a Caco-2/THP-1 Co-Culture Model

by Barbara C. Wimmer, Corinna Dwan, Jelle De Medts, Cindy Duysburgh, Chloë Rotsaert and Massimo Marzorati

Mar. Drugs 2025, 23(6), 242; https://doi.org/10.3390/md23060242 - 4 Jun 2025

Fucoidans have demonstrated a wide range of bioactivities including immune modulation and benefits in gut health. To gain a deeper understanding on the effects of fucoidan from Undaria pinnatifida (UPF) on the colonic microbiome, the short-term Simulator of the Human Intestinal Microbial Ecosystem [...] Read more.

Fucoidans have demonstrated a wide range of bioactivities including immune modulation and benefits in gut health. To gain a deeper understanding on the effects of fucoidan from Undaria pinnatifida (UPF) on the colonic microbiome, the short-term Simulator of the Human Intestinal Microbial Ecosystem^®, a validated in vitro gut model, was applied. Following a three-week intervention period on adult faecal samples from three healthy donors, microbial community activity of the colonic microbiota was assessed by quantifying short-chain fatty acids while composition was analysed utilising 16S-targeted Illumina sequencing. Metagenomic data were used to describe changes in community structure. To assess the secretion of cytokines, co-culture experiments using Caco-2 and THP1-Blue™ cells were performed. UPF supplementation over a three-week period had a profound butyrogenic effect while also enriching colonic microbial diversity, consistently stimulating saccharolytic genera, and reducing genera linked with potentially negative health effects in both regions of the colon. Mild immune modulatory effects of UPF were also observed. Colonic fermentation of UPF showed anti-inflammatory properties by inducing the secretion of the anti-inflammatory cytokines IL-6 and IL-10 in two out of three donors in the proximal and distal colon. In conclusion, UPF supplementation may provide significant gut health benefits. Full article

(This article belongs to the Special Issue Research on Marine Compounds and Inflammation)

► Show Figures

Graphical abstract

12 pages, 1750 KiB

Open AccessArticle

Catechol Siderophores from a Mangrove-Derived Bacteria Serratia marcescens F2-2 and Their Cytotoxic Activity

by Gang Zhang, Xunming Wang, Xingwang Zhang, Lin Ye, Longyang Ke, Shimin Fan, Xuan Hong, Guoqiang Li, Bingye Yang and Lianzhong Luo

Mar. Drugs 2025, 23(6), 241; https://doi.org/10.3390/md23060241 - 30 May 2025

Serratia marcescens is a common Gram-negative and facultative anaerobic bacillus that produces serratiochelins with several bioactivities. In this study, four catechol siderphores (1–4), including two new ones named serratiochelins E (1) and F (2), were [...] Read more.

Serratia marcescens is a common Gram-negative and facultative anaerobic bacillus that produces serratiochelins with several bioactivities. In this study, four catechol siderphores (1–4), including two new ones named serratiochelins E (1) and F (2), were obtained from the fermentation of a mangrove-derived bacterium, S. marcescens F2-2. The structures were elucidated with various spectroscopic methods such as NMR and HR-ESI-MS. Absolute and geometric configurations of the new compounds were established by employing quantum NMR calculations in conjunction with DP4+ probability analysis, ECD calculations, and the advanced Marfey’s method. The bioactivity test showed that serratiochelin B (3) displayed weak but selective cytotoxicity against HepG2 cancer cells with an IC₅₀ of 50.6 μmol/L and could trigger apoptosis through both Bcl-2/Bax/caspase-3 and Fas/FasL/caspase-8 signaling pathways. These findings deepen the understanding of siderophores of S. marcescens and provide a lead for research on anti-liver cancer drugs. Full article

(This article belongs to the Special Issue Advances in Secondary Metabolites from Mangrove Holobiont)

► Show Figures

Graphical abstract

5 pages, 269 KiB

Open AccessEditorial

Exploring Marine-Derived Antioxidant and Anti-Inflammatory Agents: Findings from Recent Studies

by Marzia Vasarri and Donatella Degl’Innocenti

Mar. Drugs 2025, 23(6), 240; https://doi.org/10.3390/md23060240 - 30 May 2025

The Special Issue “Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition” of Marine Drugs underscores the immense therapeutic potential embedded within our planet’s vast marine environments [...] Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

► Show Figures

Figure 1

20 pages, 1095 KiB

Open AccessArticle

Sustainable Extraction of Prospective Cosmetic Ingredients from Colombian Marine Macroalgae Using Natural Deep Eutectic Solvents

by Verónica María Tamayo-Rincón, Jhonny Colorado-Ríos, Didier Johan Alvarez-Bustamante, Vanessa Urrea-Victoria, Diana Margarita Márquez-Fernández, Constain H. Salamanca, Stefano Dall’Acqua, Leonardo Castellanos-Hernandez and Alejandro Martínez-Martínez

Mar. Drugs 2025, 23(6), 239; https://doi.org/10.3390/md23060239 - 30 May 2025

This study presents the results obtained from extracting and quantifying cosmetically valuable metabolites such as phenolic compounds and mycosporine-like amino acids (MAAs) from 12 samples of marine macroalgae collected in the Colombian Caribbean Sea. Natural deep eutectic solvents (NADESs) were prepared, physicochemically tested [...] Read more.

This study presents the results obtained from extracting and quantifying cosmetically valuable metabolites such as phenolic compounds and mycosporine-like amino acids (MAAs) from 12 samples of marine macroalgae collected in the Colombian Caribbean Sea. Natural deep eutectic solvents (NADESs) were prepared, physicochemically tested (viscosity, surface tension, pH, and conductivity), and then compared with water as the reference solvent to quantify phenolic compounds using the Folin–Ciocalteau test. With a simple extraction assay with water and ultrasound followed by ultraviolet spectral scanning the presence of MAAs was easily determined in several of the analysed samples, and then they were identified by HPLC-DAD. Hydrochloric acid solution at 5% extracted a higher content of phenolic compounds than NADES and water. The NADES that showed the highest phenolic compound extraction yield was a mixture of betaine, glucose, and water with 1:1:5 molar ratio. Sargassum cf. ramifolium and Sargassum fluitans showed the highest contents of phenolic compounds extracted with NADES, with 29.2 and 21.9 mg GAE/g DW, respectively. The results show that NADESs are an interesting alternative for the more efficient extraction of cosmetically valuable compounds such as phenolic compounds and mycosporine-type amino acids from marine macroalgae. Full article

(This article belongs to the Special Issue Nutritional Content, Biologically Active Compounds, and Correlated Health Impacts of Seaweed as a Resource for Nutraceutical, Cosmetic, and Pharmaceutical Applications)

► Show Figures

Graphical abstract

15 pages, 3835 KiB

Open AccessArticle

New Bioactive Polyketides from the Mangrove-Derived Fungus Daldinia eschscholzii HJX1P2

by Miao Yu, Yikang Qiu, Shiji Chen, Jueying Shi, Xiu Gong, Jiayi Feng, Fangru Lin, Weinv Zeng, Wenyuan Kang, Caijuan Zheng and Guolei Huang

Mar. Drugs 2025, 23(6), 238; https://doi.org/10.3390/md23060238 - 30 May 2025

Three new naphthalene–chroman dimer derivatives, daldinaphchromes A–C (1–3), two new chroman derivatives, daldichromes A (5) and B (6), along with five known compounds (4, 7–10) were isolated from the mangrove-derived [...] Read more.

Three new naphthalene–chroman dimer derivatives, daldinaphchromes A–C (1–3), two new chroman derivatives, daldichromes A (5) and B (6), along with five known compounds (4, 7–10) were isolated from the mangrove-derived fungus Daldinia eschscholzii HJX1P2. Their structures and stereochemistries were elucidated through detailed NMR and MS analyses, calculated electronic circular dichroism, and comparison with previously reported data. Compound 1 demonstrated inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells, with an IC₅₀ value of 62.9 µM, and more effectively suppressed the expression of interleukin (IL)-6 than dexamethasone. A further mechanistic study suggested that 1 could prohibit the expression of iNOS in RAW 264.7 cells, and the molecular docking study suggested a possible interaction between 1 and the iNOS protein. Compounds 7 and 8 exhibited moderate to potent DPPH radical scavenging activity, with IC₅₀ values of 117.4 and 46.2 µM, respectively, compared with the positive control ascorbic acid (IC₅₀ = 45.6 µM). Compounds 4 and 10 showed ABTS⁺ radical scavenging activity, with IC₅₀ values of 66.6 and 33.2 µM, respectively, which were equal to or lower than that of the positive control vitamin C (IC₅₀ = 59.7 µM). Compounds 1–3, 7, and 9 showed antibacterial activity against three Staphylococcus aureus strains, with MIC values of 74.4–390.6 μM. Full article

(This article belongs to the Special Issue Advances in Secondary Metabolites from Mangrove Holobiont)

► Show Figures

Figure 1

9 pages, 2313 KiB

Open AccessCommunication

The Conopeptide αD-FrXXA, an Inhibitor of Voltage-Gated Potassium Channels

by Luis Martínez-Hernández, Estuardo López-Vera, Ximena C. Rodriguez-Ruiz and Mónica A. Ortíz-Arellano

Mar. Drugs 2025, 23(6), 237; https://doi.org/10.3390/md23060237 - 30 May 2025

The conopeptide αD-FrXXA was previously isolated by our team from the venom of the vermivorous snail Conus fergusoni. This toxin is composed of two chains of 47 amino acids and inhibits neuronal and muscular subtypes of nAChR. In this study, we explored [...] Read more.

The conopeptide αD-FrXXA was previously isolated by our team from the venom of the vermivorous snail Conus fergusoni. This toxin is composed of two chains of 47 amino acids and inhibits neuronal and muscular subtypes of nAChR. In this study, we explored its effects on voltage-gated potassium channels heterologously expressed in Xenopus laevis oocytes using the two-electrode voltage-clamp technique (TEVC). At a concentration of 15 μM, αD-FrXXA was able to inhibit by 50% or more the currents of four subtypes of the Kv1 subfamily and slightly inhibit (<20%) two subtypes of the EAG subfamily. The conopeptide αD-FrXXA inhibits in a concentration-dependent manner the subtypes Kv1.3 (IC₅₀ 0.38 ± 0.06 μM) and Kv1.6 (IC₅₀ 0.52 ± 0.14 μM). The results reported here are noteworthy because this α-conopeptide behaves similarly to the α/κJ-PlXIVA conopeptide that inhibits nAChR and Kv channels. Full article

(This article belongs to the Special Issue Conotoxins: Detection, Classification and Potential Therapeutic Benefits)

► Show Figures

Graphical abstract

21 pages, 5296 KiB

Open AccessArticle

Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from Stichopus horrens and the Derivatives on P-Selectin

by Caiyi Li, Huifang Sun, Xi Gu, Wen Long, Guangyu Zhu, Xiaolu Wu, Yu Wang, Pengfei Li, Le Sha, Jiali Zhang, Wenwu Sun, Na Gao, Zhili Zuo and Jinhua Zhao

Mar. Drugs 2025, 23(6), 236; https://doi.org/10.3390/md23060236 - 30 May 2025

Unique fucosylated chondroitin sulfate (FCS) extracted from the sea cucumber Stichopus horrens was subjected to deacetylation and deaminative depolymerization to generate oligosaccharide fragments containing anTal-diol, which were further purified to obtain the trisaccharide ShFCS-3. Subsequently, the coupling of ShFCS-3 and 4-azidoaniline was achieved [...] Read more.

Unique fucosylated chondroitin sulfate (FCS) extracted from the sea cucumber Stichopus horrens was subjected to deacetylation and deaminative depolymerization to generate oligosaccharide fragments containing anTal-diol, which were further purified to obtain the trisaccharide ShFCS-3. Subsequently, the coupling of ShFCS-3 and 4-azidoaniline was achieved by reductive amination. After purification, the main product ShFCS-A1 and by-product ShFCS-A2 were obtained, which were identified as (N-(L-Fuc_2S4S-α1,3-D-GlcA-β1,3-D-anTalA_4S6S-1-)-4-azidoaniline) and (4S)-[2-(3-L-Fuc_2S4S-α1)-D-GlcA-β1]-2,4,5-trihydroxy-5-sulfated-pent-2-enoic-acid) by 1D/2D NMR spectroscopy, respectively. ELISA experiments revealed that ShFCS-A1 exhibited P-selectin inhibition rates of 19.73% ± 9.60% at 1 μM, 96.28% ± 2.37% at 10 μM, and near-complete inhibition (99.92% ± 0.84%) at 100 μM. ShFCS-A2 demonstrated inhibition rates of 8.29% ± 3.00% at 1 μM, 74.02% ± 8.80% at 10 μM, and maximal inhibition approaching 100% at 100 μM. Cellular-level experiments revealed that ShFCS-A1 and ShFCS-A2 inhibited P-selectin binding to HL-60 cells by 92.72% ± 0.85% and 96.97% ± 1.16% at 100 μM, respectively. Molecular docking analysis indicated binding energies of −5.954 kcal/mol for ShFCS-A1 and −6.140 kcal/mol for ShFCS-A2 with P-selectin, confirming their potent inhibitory effects. These findings highlight the therapeutic potential of FCS oligosaccharides as pharmacophores and provide an important foundation for developing novel small-molecule P-selectin inhibitors. Full article

(This article belongs to the Special Issue Isolation, Identification and Applications of Marine Source Polysaccharides and Peptides—2nd Edition)

► Show Figures

Figure 1

21 pages, 1684 KiB

Open AccessReview

Marine-Derived Astaxanthin: Molecular Mechanisms, Biomedical Applications, and Roles in Stem Cell Biology

by Aretha Rambaldi, Francesca Paris, Pasquale Marrazzo, Roberta Costa, Stefano Ratti and Francesco Alviano

Mar. Drugs 2025, 23(6), 235; https://doi.org/10.3390/md23060235 - 29 May 2025

Astaxanthin (ASX) is a xanthophyll carotenoid mainly derived from marine microalgae such as Haematococcus pluvialis and Chlorella zofingiensis, as well as the yeast Phaffia rhodozyma. Its chemical nature structure, rich in conjugated double bonds, carbonyl, and hydroxyl groups, confers potent antioxidant [...] Read more.

Astaxanthin (ASX) is a xanthophyll carotenoid mainly derived from marine microalgae such as Haematococcus pluvialis and Chlorella zofingiensis, as well as the yeast Phaffia rhodozyma. Its chemical nature structure, rich in conjugated double bonds, carbonyl, and hydroxyl groups, confers potent antioxidant and anti-inflammatory properties. ASX modulates oxidative stress via the PI3K/Akt-Nrf2 pathway and suppresses NF-κB-mediated inflammatory responses, reducing cytokine levels such as TNF-α, IL-6, and iNOS. ASX exerts dual apoptotic effects, cytoprotective in non-transformed cells and pro-apoptotic in cancer cells through p53 activation. Sustainable extraction techniques, especially supercritical CO₂, have improved its industrial applicability. Recent findings highlight ASX’s role in stem cell biology, enhancing proliferation, supporting lineage-specific differentiation, and protecting against oxidative and inflammatory damage, which is a crucial issue for regenerative medicine applications. These multifaceted molecular effects support ASX’s therapeutic potential in chronic diseases, including diabetes, cardiovascular pathologies, and cancer. This review outlines ASX’s natural sources, extraction methods, and biological mechanisms, emphasizing its application in oxidative stress- and inflammation-related conditions. Full article

(This article belongs to the Special Issue Recent Advances in Marine-Derived Pigments)

► Show Figures

Figure 1

14 pages, 1175 KiB

Open AccessArticle

Isolation and Identification of Cis-2,5-Diketopiperazine from a Novel Bacillus Strain and Synthesis of Its Four Stereoisomers

by Alan M. C. Obled, Refaat B. Hamed, Edward Spence, Marija K. Zacharova, Sunil V. Sharma, Yunpeng Wang, Rosemary Lynch, Helen Connaris, Adina Tatheer, Marie-Lise Bourguet-Kondracki, Gordon J. Florence and Rebecca J. M. Goss

Mar. Drugs 2025, 23(6), 234; https://doi.org/10.3390/md23060234 - 29 May 2025

The Bacillus horneckiae-like strain 2011SOCCUF3 was isolated from the marine sponge Spongia officinalis and its metabolome was studied for secondary metabolites with antimicrobial activity. Culturing in the presence of Diaion HP-20 resin and purifying the culture extract identified cyclo-phenylalanine-proline (cyclo-(Phe-Pro)), a 2,5-diketopiperazine [...] Read more.

The Bacillus horneckiae-like strain 2011SOCCUF3 was isolated from the marine sponge Spongia officinalis and its metabolome was studied for secondary metabolites with antimicrobial activity. Culturing in the presence of Diaion HP-20 resin and purifying the culture extract identified cyclo-phenylalanine-proline (cyclo-(Phe-Pro)), a 2,5-diketopiperazine (2,5-DKP), isolated as a major metabolite. Further, LCMS analysis of the extract showed the presence of two isomers of the molecule in the culture broth. To confirm the stereochemistry of the isomers observed in the natural extract, all four stereoisomers of cyclo-(Phe-Pro) were synthesised. NMR and LCMS studies identified the presence of both cis- and trans-cyclo-(Phe-Pro) isomers. Stability and epimerisation studies on synthetic isomers and the effect of culturing conditions suggested that the less stable cis isomer was naturally produced, which epimerised in culture broth. Full article

(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)

► Show Figures

Figure 1

28 pages, 831 KiB

Open AccessFeature PaperReview

Cyanobacterial Peptides in Anticancer Therapy: A Comprehensive Review of Mechanisms, Clinical Advances, and Biotechnological Innovation

by Heayyean Lee, Khuld Nihan and Yale Ryan Kwon

Mar. Drugs 2025, 23(6), 233; https://doi.org/10.3390/md23060233 - 29 May 2025

Cyanobacteria-derived peptides represent a promising class of anticancer agents due to their structural diversity and potent bioactivity. They exert cytotoxic effects through mechanisms including microtubule disruption, histone deacetylase inhibition, and apoptosis induction. Several peptides—most notably the dolastatin-derived auristatins—have achieved clinical success as cytotoxic [...] Read more.

Cyanobacteria-derived peptides represent a promising class of anticancer agents due to their structural diversity and potent bioactivity. They exert cytotoxic effects through mechanisms including microtubule disruption, histone deacetylase inhibition, and apoptosis induction. Several peptides—most notably the dolastatin-derived auristatins—have achieved clinical success as cytotoxic payloads in antibody–drug conjugates (ADCs). However, challenges such as limited tumor selectivity, systemic toxicity, and production scalability remain barriers to broader application. Recent advances in targeted delivery technologies, combination therapy strategies, synthetic biology, and genome mining offer promising solutions. Emerging data from preclinical and clinical studies highlight their therapeutic potential, particularly in treatment-resistant cancers. In this review, we (i) summarize key cyanobacterial peptides and their molecular mechanisms of action, (ii) examine progress toward clinical translation, and (iii) explore biotechnological approaches enabling sustainable production and structural diversification. We also discuss future directions for enhancing specificity and the therapeutic index to fully exploit the potential of these marine-derived peptides in oncology. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)

► Show Figures

Figure 1

19 pages, 15212 KiB

Open AccessArticle

The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor

by Jônatas Sousa Pires dos Santos, Dahara Keyse Carvalho Silva, Vanessa da Silva Oliveira, Sergio Santos Silva Junior, Edivaldo dos Santos Rodrigues, Claudia Valeria Campos de Souza, Sabrina Teixeira Martinez, Osvaldo Andrade Santos-Filho, Cássio Santana Meira and Milena Botelho Pereira Soares

Mar. Drugs 2025, 23(6), 232; https://doi.org/10.3390/md23060232 - 29 May 2025

Inflammation plays a central role in various pathological conditions, necessitating the search for safer and more effective anti-inflammatory agents. This study investigates the anti-inflammatory activity of caulerpin, a bisindolic alkaloid isolated from Caulerpa racemosa. In vitro assays demonstrated that caulerpin significantly reduced [...] Read more.

Inflammation plays a central role in various pathological conditions, necessitating the search for safer and more effective anti-inflammatory agents. This study investigates the anti-inflammatory activity of caulerpin, a bisindolic alkaloid isolated from Caulerpa racemosa. In vitro assays demonstrated that caulerpin significantly reduced nitric oxide, TNF-α, IL-6, and IL-12 levels in macrophages stimulated with LPS + IFN-γ, without affecting cell viability. In silico toxicity predictions using Protox 3.0 reinforce a favorable safety profile of caulerpin. Molecular docking and molecular dynamics simulations revealed its high-affinity binding to the glucocorticoid receptor ligand-binding domain (GR-LBD), suggesting a mechanism of action similar to dexamethasone. The involvement of the glucocorticoid receptor was confirmed by the partial reversal of caulerpin’s effects upon RU486 treatment. In vivo, caulerpin exhibited a favorable safety profile, with no signs of acute toxicity at an oral dose of 100 mg/kg. Moreover, in a mouse model of endotoxic shock, caulerpin administration significantly improved survival rates in a dose-dependent manner, providing complete protection at 4 mg/kg. These findings highlight caulerpin as a promising candidate for the development of novel anti-inflammatory therapies. Further studies are warranted to explore its pharmacokinetics, optimize its structure, and evaluate its efficacy in chronic inflammatory diseases. Full article

(This article belongs to the Special Issue Immunomodulatory Activities of Marine Products)

► Show Figures

Figure 1

20 pages, 3148 KiB

Open AccessReview

Advances in Jellyfish Sting Mechanisms and Treatment Strategies

by Bingbing Li, Yueyue Li, Zhiwen Qiu, Chuantao Zhang, Yue Li, Wei Li and Jishun Yang

Mar. Drugs 2025, 23(6), 231; https://doi.org/10.3390/md23060231 - 28 May 2025

Jellyfish stings, as one of the most prevalent forms of marine injury, have increasingly become a subject of concern. Despite their simple morphology and structure, jellyfish possess a complex venom composition that can inflict varying degrees of damage on multiple human physiological systems. [...] Read more.

Jellyfish stings, as one of the most prevalent forms of marine injury, have increasingly become a subject of concern. Despite their simple morphology and structure, jellyfish possess a complex venom composition that can inflict varying degrees of damage on multiple human physiological systems. Consequently, the clinical symptoms associated with jellyfish stings are highly intricate. Although antivenoms have been developed for certain jellyfish species (e.g., C. fleckeri), specific antivenoms targeting the mechanisms of most jellyfish venoms remain understudied. To effectively prevent, treat, and cure jellyfish stings, we adhere to the principle of knowing their nature and their reasons. It is essential to investigate the emission mechanism of jellyfish nematocysts and the composition of their venom. Understanding these factors is crucial for the development of targeted treatment strategies. This review delves into the venom emission mechanism of jellyfish stinging cells, the symptoms resulting from jellyfish stings, and the comprehensive treatment strategies post-sting. It offers a scientific reference for comprehending jellyfish stings and establishes a theoretical foundation for subsequent research endeavors. Full article

(This article belongs to the Section Marine Toxins)

► Show Figures

Graphical abstract

More Articles...

Submit to Marine Drugs Review for Marine Drugs

Journal Menu

Journal Browser

► Journal Browser

Highly Accessed Articles

View More...

Latest Books

More Books and Reprints...

E-Mail Alert

News

30 April 2025
Richard DiMarchi and Rolf Müller Share the 2024 Tu Youyou Award

11 June 2025
Marine Drugs Receives an Increased CiteScore of 10.1

10 June 2025
Meet Us at the 52^nd Annual Meeting & International Symposium (KMB 2025), 25–27 June 2025, Busan, Republic of Korea

More News & Announcements...

Topics

Propose a Topic

Topic in Biomolecules, IJMS, Molecules, Sci. Pharm., Marine Drugs, Plants

Antioxidant Activity of Natural Products—2nd Edition Topic Editors: José Virgílio Santulhão Pinela, Maria Inês Moreira Figueiredo Dias, Carla Susana Correia Pereira, Alexandra Plácido
Deadline: 30 September 2025

Topic in Agrochemicals, Agronomy, Insects, IJMS, Marine Drugs, Toxins, Agriculture, Biology

Research on Natural Bioactive Product-Based Pesticidal Agents—2nd Edition Topic Editors: Min Lv, Hui Xu
Deadline: 28 February 2026

Topic in Applied Biosciences, Applied Sciences, Fermentation, Marine Drugs, Microorganisms, Phycology

Microalgae: Current Trends in Basic Research and Applications Topic Editors: Nhuan Nghiem, Tae Hyun Kim
Deadline: 31 March 2026

Topic in Applied Biosciences, Applied Microbiology, Fermentation, Marine Drugs, Microorganisms

Microbial Cell Factories for Natural Products Topic Editors: Carlos Barreiro, Ana Ibáñez, José L. Barredo
Deadline: 31 May 2026

Conferences

Announce Your Conference

10–12 September 2025 The 3rd International Online Conference on Toxins

1–30 November 2025 The 1st International Electronic Conference on Medicinal Chemistry and Pharmaceutics

17–19 June 2025 Seagriculture EU 2025

More Conferences...

Special Issues

Propose a Special Issue

Special Issue in Marine Drugs

Antimicrobial Compounds from Marine and Island Ecosystems: Exploration, Characterization, and Application Guest Editors: Ruoyu Mao, Qingfen Guan
Deadline: 15 June 2025

Special Issue in Marine Drugs

Marine Algal Biotechnology and Applications Guest Editor: Patrizia Casella
Deadline: 15 June 2025

Special Issue in Marine Drugs

Marine Brown Algae-Derived Bioactive Polysaccharide Fucoidans Guest Editor: Hsien-Yeh Hsu
Deadline: 15 June 2025

Special Issue in Marine Drugs

Biosynthesis of Biologically Active Marine Natural Products 2025 Guest Editor: Yiguang Zhu
Deadline: 15 June 2025

More Special Issues

Topical Collections

Topical Collection in Marine Drugs

Marine Polysaccharides Collection Editor: Paola Laurienzo

Topical Collection in Marine Drugs

Bioactive Compounds from Marine Plankton Collection Editor: Georg Pohnert

Topical Collection in Marine Drugs

Marine Drugs in the Management of Metabolic Diseases Collection Editor: Ralph Urbatzka

Topical Collection in Marine Drugs

Papers from “Sino–Italian Symposium on Bioactive Natural Products” Collection Editors: Orazio Taglialatela-Scafati, Hong Wang

More Topical Collections

Back to TopTop