Marine Drugs

15 pages, 5650 KB

Open AccessArticle

Chrysogenones A–E: Malonyl-Modified Ergosterone Derivatives from Deep-Sea-Derived Penicillium sp. MCCC 3A00121 as Inhibitors of Renal Fibroblast Activation

by Zeqing Li, Lei Chen, Yuan Wang, Mengjiao Jiang, Siyu Fang, Rong Chao, Taizong Wu and Tianhua Zhong

Mar. Drugs 2026, 24(3), 121; https://doi.org/10.3390/md24030121 - 23 Mar 2026

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Abstract

Five previously undescribed steroids, chrysogenones A–E (1–5), were isolated from the deep-sea-derived Penicillium sp. MCCC 3A00121. Their chemical structures were unambiguously established through comprehensive spectroscopic analyses, density functional theory (DFT)-based electronic circular dichroism (ECD) calculations, and X-ray crystallography. Chrysogenones [...] Read more.

Five previously undescribed steroids, chrysogenones A–E (1–5), were isolated from the deep-sea-derived Penicillium sp. MCCC 3A00121. Their chemical structures were unambiguously established through comprehensive spectroscopic analyses, density functional theory (DFT)-based electronic circular dichroism (ECD) calculations, and X-ray crystallography. Chrysogenones represent a class of oxidatively modified ergosterone-type derivatives, with 1, 2, and 5 featuring an uncommon malonyl substitution at C-12 of the ergosterone skeleton. Biologically, 1–5 exhibited varying degrees of inhibitory activity against renal fibrosis, as evidenced by the downregulation of the key fibrotic markers α-smooth muscle actin (α-SMA) and collagen I (COL1A1). Among them, chrysogenone B (2) emerged as the most promising candidate, demonstrating superior potency and pronounced inhibition of activated NRK-49F cell proliferation. Integrated network pharmacology analysis and molecular docking studies further suggested that the anti-renal fibrotic effects of compound 2 may be mediated through its interaction with putative molecular targets, including AKT1, HSP90AA1, and MDM2. Full article

(This article belongs to the Special Issue From Marine Natural Products to Marine Bioproducts)

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17 pages, 2382 KB

Open AccessArticle

Impact of Pretreatment Degree and Enzyme Type on the Production of Radical Scavenging and Antiproliferative Peptides from Starfish

by Naveen Kumar Vate, Elahe Sharifi, Alessandro Coppola, Eleonora Montuori, Ingrid Undeland, Donatella de Pascale, Daniela Coppola and Mehdi Abdollahi

Mar. Drugs 2026, 24(3), 120; https://doi.org/10.3390/md24030120 - 23 Mar 2026

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Abstract

Enzymatic hydrolysis is one of the effective methods used to obtain the bioactive peptides from marine resources. This study aimed to evaluate effect of the enzyme type (Food Pro PNL (FP), Corolase8000 (C8), and Corolase7089 (C7)) and biomass pretreatment level (whole starfish (SF), [...] Read more.

Enzymatic hydrolysis is one of the effective methods used to obtain the bioactive peptides from marine resources. This study aimed to evaluate effect of the enzyme type (Food Pro PNL (FP), Corolase8000 (C8), and Corolase7089 (C7)) and biomass pretreatment level (whole starfish (SF), deproteinized (DPSF) as well as deproteinized and demineralized starfish (DPDMSF)) on the hydrolysate yield, degree of hydrolysis (DH), generated peptides’ molecular weight (MW), and in vitro radical scavenging and antiproliferative effects. Regardless of the enzyme used, deproteinization reduced the hydrolysate yield (<8% dw/ww) and DH (<5%), but also adding demineralization, in combination with C8, resulted in an equal yield (15%) and DH (>40%) to SF. However, the protein content of hydrolysates from DPSF and DPDMSF was higher than that prepared from SF. C8 was not effective in hydrolyzing SF but was the only effective enzyme in hydrolyzing DPDMSF. The peptides’ MW distribution strongly depended on the pretreatment and enzyme type, mostly ranging from 17 to 70 kDa. Glycine content was higher in hydrolysates from DPSF and DMDPSF, indicating their collagenous nature. Hydrolysates from DPSF, rich in collagenous peptides, showed medium MW but the highest radical scavenging activity. Only SF-FP hydrolysate, rich in non-collagenous peptides, showed antiproliferative activity against melanoma cancer cells. Overall, the findings demonstrate that upstream biomass pretreatment and enzyme selection directly govern the yield and bioactivity of starfish protein hydrolysates, providing a rational basis for designing starfish protein hydrolysates with targeted functional properties. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential, 5th Edition)

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17 pages, 4547 KB

Open AccessArticle

A λ-Carrageenan-Enriched Sulfated Galactan from Gigartina radula Attenuates Atopic Dermatitis via Coordinated Anti-Inflammatory and Immunomodulatory Mechanisms

by Kexin Du, Shuo Liang, Zijing Wu, Yujing Wang, Pengcheng Gao, Wei Han, Youjing Lv, Guangli Yu and Guoyun Li

Mar. Drugs 2026, 24(3), 119; https://doi.org/10.3390/md24030119 - 22 Mar 2026

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Abstract

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease driven by immune dysregulation and epidermal barrier dysfunction. Current therapeutic options are often limited by safety concerns or suboptimal tolerability. In this study, we isolated and structurally characterized GRB-H—a λ-carrageenan-enriched sulfated hybrid galactan [...] Read more.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease driven by immune dysregulation and epidermal barrier dysfunction. Current therapeutic options are often limited by safety concerns or suboptimal tolerability. In this study, we isolated and structurally characterized GRB-H—a λ-carrageenan-enriched sulfated hybrid galactan from the marine red alga Gigartina radula—as a complex polysaccharide containing κ-, ι-, μ-, ν-, and λ-carrageenan structural units, and systematically evaluated its anti-AD potential using both in vitro and in vivo models. In vitro, GRB-H significantly suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in RAW 264.7 macrophages, and reduced 2,4-dinitrochlorobenzene (DNCB)-evoked TNF-α and IL-1β expression in HaCaT keratinocytes. In a DNCB-induced murine model of AD, topical application of GRB-H markedly ameliorated skin inflammation, epidermal hyperplasia, and dermal immune cell infiltration. GRB-H treatment lowered total serum immunoglobulin E (IgE) levels, restored the imbalanced Th1/Th2 cell ratio in the spleen, and downregulated the mRNA expression of key inflammatory cytokines—including TNF-α, IL-4, IL-5, IL-31, and interferon-γ (IFN-γ)—in lesional skin. Collectively, these findings demonstrate that GRB-H alleviates AD symptoms through coordinated local anti-inflammatory and systemic immunomodulatory actions, highlighting its promise as a marine-derived candidate for the topical management of AD. Full article

(This article belongs to the Section Marine Pharmacology)

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22 pages, 2038 KB

Open AccessArticle

Biophysical Characterization of a Carotenoprotein from Marine Sponge Tedania ignis Reveals Pigment-Dependent Stability and Antibiotic Interactions

by Philippe Lima Duarte, Paulo Anderson Paiva Martins, Jéssica de Assis Duarte, Manoel Ferreira da Costa Filho, Ellen Araújo Malveira, Celso Shiniti Nagano, Alexandre Holanda Sampaio, Edson Holanda Teixeira, Rômulo Farias Carneiro and Mayron Alves de Vasconcelos

Mar. Drugs 2026, 24(3), 118; https://doi.org/10.3390/md24030118 - 21 Mar 2026

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Abstract

Carotenoproteins from marine sponges represent an underexplored class of pigment–protein complexes with distinctive structural and functional properties. Here, we report the isolation and biophysical characterization of a blue carotenoprotein from the sponge Tedania ignis, termed Ti-CP. The protein was purified and shown [...] Read more.

Carotenoproteins from marine sponges represent an underexplored class of pigment–protein complexes with distinctive structural and functional properties. Here, we report the isolation and biophysical characterization of a blue carotenoprotein from the sponge Tedania ignis, termed Ti-CP. The protein was purified and shown to consist of two closely related isoforms with molecular masses of approximately 27–29 kDa. Reverse-phase chromatography enabled separation of the apoprotein (ApoTi-CP) and its associated carotenoids, which were identified as oxygenated carotenoids consistent with astaxanthin and mytiloxanthin. Circular dichroism analysis revealed that both Ti-CP and ApoTi-CP are dominated by β-sheet secondary structure and display highly similar conformational profiles. In contrast, dynamic light scattering demonstrated that carotenoid binding is critical for protein stability, as the native form exhibited a compact and monodisperse organization, whereas ApoTi-CP showed pronounced aggregation. Isothermal titration calorimetry revealed that Ti-CP, but not ApoTi-CP, interacts with tetracycline, oxacillin, and streptomycin, indicating that pigment-mediated stabilization modulates ligand binding. Both Ti-CP and ApoTi-CP reduced bacterial viability and biofilm formation in a strain-dependent manner and enhanced antibiotic activity, including synergistic effects against resistant bacteria. Together, these results provide a comprehensive description of a previously uncharacterized sponge carotenoprotein and highlight the dual role of carotenoids in structural stabilization and antimicrobial modulation, reinforcing the biotechnological relevance of marine pigment–protein complexes. Full article

(This article belongs to the Section Marine Chemoecology for Drug Discovery)

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15 pages, 2034 KB

Open AccessArticle

Chlokamycins B–D: Chlorohydrin-Containing Polycyclic Tetramate Macrolactams with Cytotoxic Activity from the Marine Sponge-Derived Streptomyces xiamenensis 1310KO-148

by Min Ah Lee, Jong Soon Kang, Joo-Hee Kwon, Jeong-Wook Yang, Hwa-Sun Lee, Chang-Su Heo and Hee Jae Shin

Mar. Drugs 2026, 24(3), 117; https://doi.org/10.3390/md24030117 - 21 Mar 2026

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Abstract

Chemical investigation of the marine sponge-derived Streptomyces xiamenensis 1310KO-148 afforded six polycyclic tetramate macrolactams (PTMs), including three known compounds (1–3) and three previously undescribed chlorohydrin-containing analogues, chlokamycins B–D (4–6). Their planar structures were elucidated by [...] Read more.

Chemical investigation of the marine sponge-derived Streptomyces xiamenensis 1310KO-148 afforded six polycyclic tetramate macrolactams (PTMs), including three known compounds (1–3) and three previously undescribed chlorohydrin-containing analogues, chlokamycins B–D (4–6). Their planar structures were elucidated by extensive analysis of 1D and 2D NMR spectra and HR-ESIMS data, while the relative configurations were assigned using NOESY correlations. The absolute configurations were further confirmed by electronic circular dichroism (ECD) calculations. Compounds 3–6 exhibited significant cytotoxic activity against 14 human cancer cell lines (GI₅₀ = 2.68–24.92 μM) and antibacterial activity against Staphylococcus aureus (MIC = 16.00–32.00 μg/mL) and Micrococcus luteus (MIC = 4.00–32.00 μg/mL) among six tested bacterial strains. Full article

(This article belongs to the Special Issue Bioactive Secondary Metabolites from Marine Fungi and Actinomycetes)

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35 pages, 3897 KB

Open AccessReview

Marine Bioactive Compounds from Functional Seafoods: Pharmacological Mechanisms and Health Applications

by Sena Davran Bulut, Naciye Yaktubay Döndaş, Senanur Koçhan, Beyza Nur Arslan, Mehmet Ali Tamer, Mirsade Osmani, Safa Baraketi, Khaoula Khwaldia, Ziye Zhang, Hacı Ali Döndaş, Tuba Esatbeyoglu, Panagiota Katikou and Fatih Ozogul

Mar. Drugs 2026, 24(3), 116; https://doi.org/10.3390/md24030116 - 20 Mar 2026

Viewed by 678

Abstract

Functional seafoods derived from marine organisms, including fish, shellfish and algae, are gaining increasing attention due to their high content of bioactive compounds, such as omega-3 fatty acids, peptides, polysaccharides and antioxidants, which provide health benefits beyond basic nutrition. These marine-derived compounds exhibit [...] Read more.

Functional seafoods derived from marine organisms, including fish, shellfish and algae, are gaining increasing attention due to their high content of bioactive compounds, such as omega-3 fatty acids, peptides, polysaccharides and antioxidants, which provide health benefits beyond basic nutrition. These marine-derived compounds exhibit a wide range of biological activities and have been investigated for their potential roles in the prevention and management of chronic diseases, including cardiovascular, neurodegenerative, cancer and gastrointestinal disorders. Their effects are largely mediated through anti-inflammatory, antioxidant and immunomodulatory mechanisms. Advances in biotechnology, including genetic engineering and improved extraction of bioactive compounds, have enhanced the nutritional quality and pharmacological relevance of functional seafoods. At the same time, sustainable aquaculture practices are being developed to reduce environmental impacts. Nevertheless, challenges such as regulatory inconsistencies, scalability issues and limited understanding of bioavailability and long-term effects still persist. These constraints should be considered when interpreting mechanistic and efficacy findings presented across different study designs and exposure conditions. Future perspectives highlight innovations in precision aquaculture, waste valorisation and traceability as key strategies to improve sustainability and strengthen consumer trust. This review summarizes current knowledge on functional seafoods, with emphasis on pharmacological mechanisms, clinical applications and the need for interdisciplinary research to optimize their health benefits and commercial potential. Full article

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

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18 pages, 4852 KB

Open AccessArticle

Identification of an Unpredicted GAG-PUL in Roseihalotalea indica gen. nov. sp. nov. TK19036^T and Characterization of Novel GAG-Lyases with Unique Substrate Specificities

by Zheng Fu, Defang Wu, Shunqin You, Kai Tang, Runying Zeng and Zhuhua Chan

Mar. Drugs 2026, 24(3), 115; https://doi.org/10.3390/md24030115 - 20 Mar 2026

Viewed by 349

Abstract

Glycosaminoglycans (GAGs) and their degrading enzymes have extensive applications and biotechnology and medicine, and play a crucial role in the recycling of organic matter in oceans. In this study, a potential GAG utilization gene cluster was identified in the genome of a novel [...] Read more.

Glycosaminoglycans (GAGs) and their degrading enzymes have extensive applications and biotechnology and medicine, and play a crucial role in the recycling of organic matter in oceans. In this study, a potential GAG utilization gene cluster was identified in the genome of a novel marine Bacteroidetes, Roseihalotalea indica gen. nov. sp. nov. TK19036^T, through sole carbon source cultivation and differential proteomic analysis. Multiple GAG-lyases within this locus were purified and characterized. RiPL8 comprises a functionally unknown N-terminal domain and a catalytic C-terminal domain, exhibiting specificity for degrading hyaluronic acid (HA). The activity of RiPL35 is sensitive to Ca²⁺ ion concentration with an optimum at 10 mM. RiPL38 is the first reported member of the PL38 family capable of degrading HA and chondroitin sulfate (CS). In summary, our study reveals Roseihalotalea indica gen. nov. sp. nov. TK19036^T harbors an unpredicted GAG degradation gene cluster, and the encoded GAG-lyases exhibit distinct substrate specificities compared to the host organism. Full article

(This article belongs to the Special Issue Enzymes Derived from Marine Sources)

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17 pages, 1051 KB

Open AccessArticle

Effects of Different Culture Conditions on the Synthesis and Distribution of Polyunsaturated Fatty Acids (EPA and ARA) in Porphyridium purpureum

by Tao Li, Bingqi Xu, Yiyang Wu, Liang Wei, Hualian Wu, Houbo Wu, Wenzhou Xiang and Jin Xu

Mar. Drugs 2026, 24(3), 114; https://doi.org/10.3390/md24030114 - 19 Mar 2026

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Abstract

The arachidonic acid (C20:4 ω6, ARA) and eicosapentaenoic acid (C20:5 ω3, EPA) from Porphyridium purpureum endow this microalga with potential utilization value, but their distribution patterns remain poorly understood. In this study, a nitrogen concentration, a phosphorus concentration, light intensity and salinity were [...] Read more.

The arachidonic acid (C20:4 ω6, ARA) and eicosapentaenoic acid (C20:5 ω3, EPA) from Porphyridium purpureum endow this microalga with potential utilization value, but their distribution patterns remain poorly understood. In this study, a nitrogen concentration, a phosphorus concentration, light intensity and salinity were applied to investigate the synthesis and distribution patterns of EPA and ARA in P. purpureum by measuring growth, lipid content, lipid fractions, fatty acid composition, and the levels of EPA and ARA in storage lipids and membrane lipids. The results show that the optimal conditions for biomass accumulation were a nitrogen concentration of 0.75 g L⁻¹, a phosphorus concentration of 240 mg L⁻¹, a light intensity of 250–300 μmol photons m⁻² s⁻¹ and a salinity of 50 ppt. Reducing the phosphorus concentration and increasing salinity enhanced the total lipid content, whereas changes in nitrogen concentration and light intensity had minimal effects on total lipid content. Low nitrogen concentration, low phosphorus concentration and high light intensity favored ARA synthesis, whereas the opposite conditions promoted EPA synthesis. Culture conditions could alter the distribution of ARA and EPA between storage lipids and membrane lipids. Increasing the nitrogen concentration, phosphorus concentration and salinity, as well as reducing light intensity, promoted the distribution of ARA and EPA in membrane lipids. Conversely, the opposite conditions enhanced their distribution in storage lipids. In conclusion, the synthesis and distribution of EPA and ARA in P. purpureum are influenced by culture conditions. To improve the yield of ARA and EPA, P. purpureum should be cultivated under nutrient-sufficient conditions. Full article

(This article belongs to the Special Issue Innovations in Marine Algal Biotechnology: From Bioprocessing to Applications)

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59 pages, 10722 KB

Open AccessReview

Life with Boron: Steroid Architecture and the Chemistry of Marine Boronosteroids

by Valery M. Dembitsky, Alexander O. Terent’ev, Sergey V. Baranin and Romulus I. Scorei

Mar. Drugs 2026, 24(3), 113; https://doi.org/10.3390/md24030113 - 19 Mar 2026

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Abstract

Marine invertebrates produce a remarkable diversity of polyhydroxylated steroids and secosteroids whose structural features—particularly vicinal (1,2-)diols, 1,3-diols, and clustered hydroxyl arrays—make them well suited for coordination with boron species. In the marine environment, where boron is abundant, chemically stable, and predominantly present as [...] Read more.

Marine invertebrates produce a remarkable diversity of polyhydroxylated steroids and secosteroids whose structural features—particularly vicinal (1,2-)diols, 1,3-diols, and clustered hydroxyl arrays—make them well suited for coordination with boron species. In the marine environment, where boron is abundant, chemically stable, and predominantly present as borate under mildly alkaline conditions, such interactions are not only plausible but may be widespread. This review examines the chemistry of boron–steroid complexation in marine systems, emphasizing how rigid steroidal frameworks preorganize diol motifs to form reversible yet stable borate esters under environmentally relevant conditions. We discuss how polyhydroxy steroids may exist in dynamic equilibria between free and boron-bound forms, with speciation governed by pH, boron concentration, and local microenvironmental factors rather than enzymatic control. Boron complexation can modulate key physicochemical properties, including solubility, conformation, and membrane affinity, thereby influencing the biological activity of marine steroids without covalent modification of the carbon framework. By integrating examples from sponges, echinoderms, and corals together with well-characterized model polyols, this review highlights boron complexation as an underrecognized but potentially important factor influencing the structure, function, and bioactivity of marine steroid metabolites. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

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17 pages, 6283 KB

Open AccessArticle

Isaridin E Protects Against UVB-Induced Photoaging by Activating Wnt/β-Catenin Signaling Pathway and Alleviating Mitochondrial Dysfunction

by Yaosheng Liu, Weizhen Li, Zeen Yang, Hui Long, Sufen Cai, Changjie Sun, Yu Xiong, Yunqi Zhang, Yumei Liu, Guangpu Luo, Senhua Chen and Tie Zhao

Mar. Drugs 2026, 24(3), 112; https://doi.org/10.3390/md24030112 - 18 Mar 2026

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Abstract

Mitochondrial dysfunction is a major contributor to skin photoaging. Activation of the Wnt/β-catenin pathway, a key regulator of developmental processes, can improve mitochondrial abnormalities associated with pathology. Therefore, the Wnt/β-catenin pathway emerges as a key therapeutic target in the context of photoaging. Isaridin [...] Read more.

Mitochondrial dysfunction is a major contributor to skin photoaging. Activation of the Wnt/β-catenin pathway, a key regulator of developmental processes, can improve mitochondrial abnormalities associated with pathology. Therefore, the Wnt/β-catenin pathway emerges as a key therapeutic target in the context of photoaging. Isaridin E (ISE), a marine-derived natural product with a novel structure, exhibits potent antiplatelet and anti-inflammatory activities. We sought to examine the anti-senescence effects of ISE on fibroblasts in photoaged skin. In vitro, ISE improved UVB-induced fibroblast damage in a dose-dependent manner, restoring cell viability, reducing β-galactosidase accumulation, and suppressing SASP factor production. In a photoaging mouse model, ISE markedly decreased skin thickness, increased dermal collagen expression, and reduced SASP levels in skin tissues. ISE significantly improved fibroblast energy production deficits and mitochondrial dysfunction. RNA sequencing and Western blotting demonstrated that UVB irradiation significantly suppressed Wnt/β-catenin signaling activity, whereas ISE dose-dependently restored pathway activation. Using GSK-3β-targeted siRNA, we showed that the anti-photoaging effects of ISE are mediated via the Wnt/β-catenin pathway. ISE appears to counteract photoaging by enhancing Wnt/β-catenin activity and improving mitochondrial function. Full article

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

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15 pages, 1030 KB

Open AccessArticle

New Cyclopeptides and Curvularins from Marine-Derived Fungal-Bacterial Symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532

by Fei-Hua Yao, Jie Yang, Xiao-Yan Li, Shu-Fen Xu, Kai Liu, Zhen-Zhou Tang, Wei-Hui Li, Yong-Hong Liu, Xiang-Xi Yi and Cheng-Hai Gao

Mar. Drugs 2026, 24(3), 111; https://doi.org/10.3390/md24030111 - 15 Mar 2026

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Abstract

Three new cyclic tetrapeptides (nectriatidels A-C, 1–3), two new curvularin analogs (6 and 7), and four known compounds (4 and 5, 8 and 9) were isolated from the marine-derived fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/ [...] Read more.

Three new cyclic tetrapeptides (nectriatidels A-C, 1–3), two new curvularin analogs (6 and 7), and four known compounds (4 and 5, 8 and 9) were isolated from the marine-derived fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532, which was obtained from Mauritia arabica in shallow coastal waters. Their structures were elucidated through NMR spectroscopy and HRESIMS, and their absolute configurations were determined by Marfey’s method and quantum chemical calculations. Compounds 1–5 showed moderate amphotericin B (AmB)-potentiating activity against Candida albicans. Compounds 7 and 8 exhibited significant activities against Mycobacterium tuberculosis, with MIC values of 32 and 16 μg/mL, respectively. Additionally, compounds 7 and 8 exhibited moderate cytotoxicity against human colorectal cancer cell lines DLD-1 and SW480, with IC₅₀ values of 25~36 μM. Whole-genome sequencing of A. spelaeus revealed a 35.91 Mb assembly encoding 106 biosynthetic gene clusters (BGCs). antiSMASH analysis revealed that 79 of these BGCs (74.5%) displayed no significant similarity to known pathways in the MIBiG database, which is dominated by hybrid clusters, terpene, T1PKS, NRPS, and NRPS-like types. Genomic analysis identified the putative biosynthetic gene clusters for these metabolites and confirmed the fungal host as the predominant producer. Full article

(This article belongs to the Special Issue Bioactivities of Coastal Organism-Derived Marine Natural Products)

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17 pages, 2042 KB

Open AccessReview

The Chemistry and Pharmacology of the Alkaloid Barettin and Its Analogues from the Marine Sponge Geodia barretti: Progress and Perspectives

by Christian Bailly

Mar. Drugs 2026, 24(3), 110; https://doi.org/10.3390/md24030110 - 13 Mar 2026

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Abstract

The cold-water siliceous sponge Geodia barretti, largely present in the North Atlantic Ocean, notably around Scandinavian costs, plays important roles in carbon and silicon cycling in the deep-sea. The demosponge provides a reservoir for numerous microorganisms. Bioactive natural products have been isolated [...] Read more.

The cold-water siliceous sponge Geodia barretti, largely present in the North Atlantic Ocean, notably around Scandinavian costs, plays important roles in carbon and silicon cycling in the deep-sea. The demosponge provides a reservoir for numerous microorganisms. Bioactive natural products have been isolated from this sponge, in particular the indole alkaloid barettin discovered forty years ago. Barettin and analogues, notably 8,9-dihydrobarettin, 8,9-dihydro-8-hydroxybarrettin, bromobenzisoxalone barettin, and geobarrettins A-B, contribute to the maintenance of the sponge stability and security (anti-fouling) and the regulation of its microbial environment. The four indole alkaloids 6-bromo-8-hydroxyconicamin, 6-bromoconicamin, and geobarrettin C-D are also implicated in the defense of the sponge against physical and biochemical aggressions. Altogether, these ten natural products are essential to the sponge life. The present review presents a survey of the chemistry and biology associated with Geodia barretti. The pharmacological properties of (dihydro)barettin, notably their antioxidant and anti-inflammatory properties, are discussed, as well as the synthetic processes set up to produce these diketopiperazine derivatives. Their molecular targets and mechanism of action are also discussed. The review takes the sponge G. barretti from the depths of knowledge and brings barettin and analogues to the surface, with the hope of guiding future research in this field. Full article

(This article belongs to the Section Marine Pharmacology)

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28 pages, 5114 KB

Open AccessArticle

Isolation, Characterization and Biological Evaluation of Collagen from Rhizostoma pulmo Jellyfish from the Sea of Azov for Biomedical Applications

by Oleg Kit, Sergey Golovin, Evgeniya Kirichenko, Alina Sereda, Yulia Gordeeva, Evgeniy Sadyrin, Andrey Nikolaev, Pavel Antipov, Aleksandr Logvinov, Maria Kaplya, Magomed Abdulkadyrov and Stanislav Rodkin

Mar. Drugs 2026, 24(3), 109; https://doi.org/10.3390/md24030109 - 13 Mar 2026

Viewed by 571

Abstract

Collagen is a major extracellular-matrix protein widely used in regenerative medicine, yet conventional terrestrial sources raise biosafety and acceptability concerns, motivating the search for marine alternatives. This study evaluates the jellyfish Rhizostoma pulmo (R. pulmo) from the Azov Sea as a [...] Read more.

Collagen is a major extracellular-matrix protein widely used in regenerative medicine, yet conventional terrestrial sources raise biosafety and acceptability concerns, motivating the search for marine alternatives. This study evaluates the jellyfish Rhizostoma pulmo (R. pulmo) from the Azov Sea as a sustainable collagen source and assesses its suitability for biomedical materials. Acid-soluble collagen was extracted using 0.5 M acetic acid and purified by salt precipitation and dialysis, followed by physicochemical/structural characterization (sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE), Limulus amebocyte lysate (LAL) endotoxin testing, transmission electron microscopy (TEM), and immunofluorescence with type I collagen antibodies) and biological evaluation in vitro (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity on MRC5 fibroblasts; adhesion and proliferation assays on HeLa cells). The extracted collagen showed a high yield (~26.2%), a type I-like electrophoretic profile with α-, β-, and γ-components, fibrillar ultrastructure by TEM, and positive type I collagen immunoreactivity; endotoxin levels were low (0.461 EU/µL), and no cytotoxicity was detected under the tested conditions. Porous collagen sponges/scaffolds were fabricated by lyophilization, displaying interconnected pores with an average size of ~80 µm and pH-dependent swelling, and they supported 3D cell growth and tumor-cell dissemination in an in vitro breast carcinoma scaffold model. Overall, Azov Sea R. pulmo collagen demonstrates promising structural quality, low endotoxin burden, and cytocompatibility, supporting its potential as a marine biomaterial for sponge/scaffold-based tissue engineering and wound-related applications. Full article

(This article belongs to the Special Issue Jellyfish-Derived Compounds)

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15 pages, 2198 KB

Open AccessArticle

Novel Marine Fungus-Derived Mycophenolic Acids That Inhibit Acute Myeloid Leukemia Cell Proliferation

by Guangli Deng, Wu Ruan, Qun Li, Qingyun Peng, Yunan Liu, Lingbin Lin, Yuan Li, Qianqian Shen, Yangrong Zhao, Junfeng Wang, Yi Chen and Ming-Wei Wang

Mar. Drugs 2026, 24(3), 108; https://doi.org/10.3390/md24030108 - 13 Mar 2026

Viewed by 424

Abstract

Nine new mycophenolic acid derivatives, penicacids O–W (1–9), two first-time reported natural products (10, 11), and five known compounds (12–16), were isolated from a marine-derived fungus Penicillium senticosum RCDB005 found in a [...] Read more.

Nine new mycophenolic acid derivatives, penicacids O–W (1–9), two first-time reported natural products (10, 11), and five known compounds (12–16), were isolated from a marine-derived fungus Penicillium senticosum RCDB005 found in a South China Sea sediment sample. Their structures were determined using NMR, HRESIMS, and optical rotatory dispersion (ORD) spectra, electronic circular dichroism (ECD) calculations, X-ray crystallography, and modified Mosher’s methods. Eight of these compounds were evaluated for anti-proliferative effects against nine human cancer cell lines and the IC₅₀ values ranged from nM to μM levels. Compounds 5, 7–9 showed potent inhibition activity against MOLM-13 acute myeloid leukemia cells with IC₅₀ values between 0.13 and 1.13 μM. Full article

(This article belongs to the Special Issue Bioactive Secondary Metabolites from Marine Fungi and Actinomycetes)

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16 pages, 1615 KB

Open AccessArticle

Microalgal Exosome-like Nanovesicles from Nannochloropsis oculata Attenuate Melanogenesis Through Tyrosinase Inhibition in B16-F10 Melanoma Cells

by Liangquan Xie, Chaoxuan Wu, Weilin Du, Jiaying Chen, Zijie He, Tingting Li, Chuangye Yang, Yuewen Deng and Zhe Zheng

Mar. Drugs 2026, 24(3), 107; https://doi.org/10.3390/md24030107 - 12 Mar 2026

Viewed by 519

Abstract

As primary producers in aquatic ecosystems, microalgae function not only as a natural source of nourishment for several economically important aquatic species but also as reservoirs of bioactive molecules. Microalgae can secrete exosome-like nanoparticles that transport functional biomolecules, such as proteins and nucleic [...] Read more.

As primary producers in aquatic ecosystems, microalgae function not only as a natural source of nourishment for several economically important aquatic species but also as reservoirs of bioactive molecules. Microalgae can secrete exosome-like nanoparticles that transport functional biomolecules, such as proteins and nucleic acids, into the extracellular milieu, thereby mediating intercellular signaling and eliciting ecological or biomedical responses. Although plant-derived exosome-like nanoparticles have attracted attention for their utility in drug delivery and dermatology, the functional properties of microalgae-derived nanoparticles—particularly from species extensively applied in aquaculture—remain inadequately characterized. In this study, exosome-like nanovesicles were isolated from Nannochloropsis oculata (N-ELNs), a microalgal species widely used in aquaculture, and their skin-whitening potential was evaluated using the B16-F10 mouse melanoma cell model. The highest N-ELN yield was observed during the adaptation, exponential, and stationary growth phases. Uptake analyses confirmed the efficient internalization of N-ELNs by B16-F10 cells. Cell counting kit-8 assays indicated that N-ELNs exhibited no cytotoxic effects on melanoma cells or normal human dermal fibroblasts (HFF-1). Scratch wound healing assays revealed that N-ELNs exerted no significant effect on cellular migration. In B16-F10 cells, N-ELNs suppressed tyrosinase activity by downregulating Mitf and its downstream genes Tyr and Tyrp1, resulting in a substantial reduction in melanin synthesis (p < 0.05). The inhibitory effects of N-ELNs on melanin production, tyrosinase activity, and gene expression of Tyr, Tyrp1, and Mitf were comparable to those of the positive control, arbutin. Collectively, these findings suggest that N. oculata exhibits promising skin-whitening properties, providing a novel perspective for clinical applications and supporting the high-value utilization of the microalgae aquaculture industry. Full article

(This article belongs to the Special Issue Algae-Powered Skincare: Innovations in Marine-Derived Cosmeceuticals)

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15 pages, 4919 KB

Open AccessArticle

Screening and Evaluation of Chassis Cells for Heterologous Biosynthesis of Gas Vesicles as Ultrasound Contrast Agents

by Qiuxia Fu, Kezhi Yu, Yuanyuan Wang, Chenxing Liu, Wei Liu, Wenze Ou, Wei Sun and Fei Yan

Mar. Drugs 2026, 24(3), 106; https://doi.org/10.3390/md24030106 - 11 Mar 2026

Viewed by 438

Abstract

Gas vesicles (GVs) are hollow protein nanostructures derived from microorganisms and show significant potential for ultrasound imaging applications. However, the direct production of gas vesicles (GVs) from their native hosts faces several limitations: poor contrast imaging performance, insufficient yield, and high costs associated [...] Read more.

Gas vesicles (GVs) are hollow protein nanostructures derived from microorganisms and show significant potential for ultrasound imaging applications. However, the direct production of gas vesicles (GVs) from their native hosts faces several limitations: poor contrast imaging performance, insufficient yield, and high costs associated with extraction and purification. These challenges heavily hinder their clinical translation and application. The heterologous expression of GV genes varies significantly among different chassis strains due to their distinct intracellular environments, which ultimately affects GV performance and yield. Therefore, it is crucial to select an appropriate chassis cell that can produce GVs with excellent imaging performance. In this study, the GV gene cluster from Serratia sp. ATCC 39006 was heterologously expressed in five different bacterial chassis strains: Escherichia coli BL21 (AI), Escherichia coli K-12 MG1655, Escherichia coli Nissle 1917, Salmonella YB1, and Vibrio natriegens. By systematically comparing the yield, particle morphology, and ultrasound imaging performance of GVs produced by these strains, we elucidated the impact of chassis cells on GV synthesis and function. This work provides experimental evidence and theoretical support for screening robust GV-producing strains and facilitates future biomedical applications of GVs. Full article

(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)

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16 pages, 2491 KB

Open AccessArticle

Exploration of Carotenoid-Producing Microorganisms from the Kuril-Kamchatka Trench and Their Antioxidant Potential

by Guan-Yuan Zhang, Xue-Gong Li, Hai-Rong Fang, Jin-Wei Gao and Wei-Jia Zhang

Mar. Drugs 2026, 24(3), 105; https://doi.org/10.3390/md24030105 - 11 Mar 2026

Viewed by 1169

Abstract

Despite its extreme conditions, the hadal environment harbors abundant but largely underexplored microbial resources. In this study, samples from the Kuril-Kamchatka Trench (KKT) were enriched at low temperature using R2A and 2216E media. Carotenoid-producing microorganisms (CPMs) were isolated from approximately one-third of the [...] Read more.

Despite its extreme conditions, the hadal environment harbors abundant but largely underexplored microbial resources. In this study, samples from the Kuril-Kamchatka Trench (KKT) were enriched at low temperature using R2A and 2216E media. Carotenoid-producing microorganisms (CPMs) were isolated from approximately one-third of the samples, yielding a total of 124 isolated strains spanning 4 phyla and 11 genera. Planococcus, Kocuria, Paracoccus, and Exiguobacterium collectively accounted for 75.8% of the isolates. The choice of culture medium significantly influenced CPM diversity at the family and genus levels, though not at the phylum or class level. Water depth, sample type, and sediment layer also significantly affected CPM community structure. Carotenoid spectral profiles correlated with phylogenetic lineage, and closer phylogenetic relationships corresponded to greater similarity in carotenoid biosynthesis gene clusters. Antioxidant assays (FRAP, ABTS, DPPH) demonstrated strong total antioxidant and radical scavenging capacities in carotenoid extracts from Citricoccus, Kocuria, Arthrobacter, and Olleya. Scavenging activity toward ABTS or DPPH radicals varied significantly among genera, suggesting genus-specific antioxidant mechanisms. These findings highlight the hadal zone as a promising reservoir of diverse CPMs and a valuable source of novel carotenoids and antioxidant-producing strains with potential biotechnological applications. Full article

(This article belongs to the Special Issue Marine Extremophiles and Their Metabolites)

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18 pages, 2105 KB

Open AccessArticle

Halamphora sp. Reduces Inflammation in LPS-Stimulated Human Malignant Melanoma and Immortalized Keratinocytes Influencing TNF-α Release

by Eleonora Montuori, Espen Holst Hansen, Calum J. McMullen, Katja Rietdorf, Carlos Almeida, Antera Martel Quintana, Assunta Saide and Chiara Lauritano

Mar. Drugs 2026, 24(3), 104; https://doi.org/10.3390/md24030104 - 10 Mar 2026

Viewed by 506

Abstract

Malignant melanoma is skin cancer arising from genetically altered melanocytes. Recently, a complex relationship between melanoma and chronic inflammation has been highlighted, representing an excellent condition for tumor development. Microalgae have been shown to be a promising source of bioactive compounds for drug [...] Read more.

Malignant melanoma is skin cancer arising from genetically altered melanocytes. Recently, a complex relationship between melanoma and chronic inflammation has been highlighted, representing an excellent condition for tumor development. Microalgae have been shown to be a promising source of bioactive compounds for drug discovery. In this study, we investigated Halamphora sp. (BEA0050) to identify possible compounds with immunomodulatory activity. The most active fraction (fraction D) showed anti-inflammatory activity against human melanoma cancer cells (A2058) stimulated using lipopolysaccharide (LPS) to induce an inflammatory phenotype. Chemical profiling of the bioactive fraction using chromatography and high-resolution mass spectrometry (UHPLC-HR-MS) revealed hydroxypheophorbide a, a breakdown product of chlorophyll a. In order to investigate the mechanism of action, the TNF-α release was detected through ELISA sandwich assays in A2058 cells and through confocal microscopy in LPS-stimulated HaCaT cells. Gene expression of principal pro-inflammatory cytokines and pathways was detected through real-time PCR, which showed the down-regulation of the inflammatory pathway in LPS-induced A2058 and HaCaT cells treated with 12.5 µg/mL of fraction D. This study reports for the first time the anti-melanoma and anti-inflammatory activities of Halamphora sp., identifying protein mediators and highlighting its biotechnological potential. Full article

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

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12 pages, 1671 KB

Open AccessArticle

Targeted Inactivation of an α/β Hydrolase Gene Enables Discovery of Heterodimeric Nenestatins

by Wenzheng Wei, Xiaodong Jiang, Yiguang Zhu, Wenjun Zhang, Chunfang Yang, Qingbo Zhang and Changsheng Zhang

Mar. Drugs 2026, 24(3), 103; https://doi.org/10.3390/md24030103 - 8 Mar 2026

Viewed by 422

Abstract

Nenestatins (NENs) belong to benzo[b]fluorene-containing atypical angucyclines, a structurally diverse class of microbial natural products. Bioinformatic analysis of the NEN biosynthetic gene cluster (nes BGC) from the deep-sea sediment-derived Micromonospora echinospora SCSIO 04089 implicated Nes5 as an α/β hydrolase. The [...] Read more.

Nenestatins (NENs) belong to benzo[b]fluorene-containing atypical angucyclines, a structurally diverse class of microbial natural products. Bioinformatic analysis of the NEN biosynthetic gene cluster (nes BGC) from the deep-sea sediment-derived Micromonospora echinospora SCSIO 04089 implicated Nes5 as an α/β hydrolase. The targeted inactivation of the nes5 gene led to the accumulation of five new analogs, NENs E–I (1–5), together with the known monomer homo-dehydrorabelomycin E (6). Their structures were elucidated by comprehensive spectroscopic analysis and electronic circular dichroism calculations. Notably, both NEN A and NEN B were absent in the Δnes5 mutant, indicating that Nes5 is essential for their biosynthesis; however, the exact function of Nes5 requires further exploration. Full article

(This article belongs to the Section Marine Pharmacology)

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35 pages, 2001 KB

Open AccessReview

Marine Lectins in Innate Immune Modulation: Mechanistic Insights, Signaling Pathways, and a Cross-Taxa Evidence Landscape

by Chang-Eui Hong and Su-Yun Lyu

Mar. Drugs 2026, 24(3), 102; https://doi.org/10.3390/md24030102 - 6 Mar 2026

Viewed by 595

Abstract

Marine lectins function as pattern recognition receptors in innate immunity through carbohydrate-binding mechanisms. However, mechanistic evidence detailing intracellular signaling cascades (e.g., MAPK/NF-κB/JAK-STAT activation linked to defined cytokine outputs) remains taxonomically uneven. Bivalve mollusks—particularly the Mytilectin family—represent the most extensively characterized group, whereas lectins [...] Read more.

Marine lectins function as pattern recognition receptors in innate immunity through carbohydrate-binding mechanisms. However, mechanistic evidence detailing intracellular signaling cascades (e.g., MAPK/NF-κB/JAK-STAT activation linked to defined cytokine outputs) remains taxonomically uneven. Bivalve mollusks—particularly the Mytilectin family—represent the most extensively characterized group, whereas lectins from other marine phyla (echinoderms, cnidarians, fish, algae) have been studied primarily for structural and glycan-binding properties alongside phenotypic antimicrobial outcomes. Signaling-level resolution in native immune-cell contexts, while present in some cases, remains comparatively limited. This review synthesizes mechanistic insights dominated by bivalve-derived lectins, while integrating cross-taxa comparisons at evidence-supported levels. Specific bivalve lectins induce macrophage activation and pro-inflammatory cytokine production through reactive oxygen species-dependent activation of key signaling pathways including MAPK, NF-κB, and JAK-STAT cascades. These lectins exhibit context-dependent properties, promoting inflammatory responses in resting cells while inducing endotoxin tolerance in pre-activated macrophages through epigenetic reprogramming. Functional outcomes include broad-spectrum antiviral activity through viral envelope glycoprotein binding, anti-inflammatory effects in pain models, and cancer-associated immune responses through tumor glycan recognition and macrophage polarization. Critical gaps include uncharacterized effects on adaptive immunity, limited understanding of dendritic cell and natural killer cell interactions, and incomplete evaluation of cancer immunotherapy potential. Future research should prioritize mechanistic characterization of marine lectin-based immunotherapeutics. Full article

(This article belongs to the Section Marine Pharmacology)

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12 pages, 915 KB

Open AccessReview

Astaxanthin as a Therapeutic Candidate for Nociceptive and Inflammatory Pain: Mechanisms and Perspectives

by Mamoru Takeda and Risako Chida

Mar. Drugs 2026, 24(3), 101; https://doi.org/10.3390/md24030101 - 3 Mar 2026

Viewed by 660

Abstract

Recently, complementary and alternative medicine (CAM) has been actively employed for patients experiencing symptoms unresponsive to Western medical treatments like drug therapy. The natural compounds carotenoids and astaxanthin (AST) have demonstrated various beneficial biological actions for human health in several studies. Given their [...] Read more.

Recently, complementary and alternative medicine (CAM) has been actively employed for patients experiencing symptoms unresponsive to Western medical treatments like drug therapy. The natural compounds carotenoids and astaxanthin (AST) have demonstrated various beneficial biological actions for human health in several studies. Given their broad pharmacological activities and reduced toxicity, ASTs possess significant potential as resources for the development of natural analgesic drugs. Given recent studies showing that AST can modulate neuronal excitability, including nociceptive sensory transmission through voltage-gated Ca²⁺ channels and the n-methyl-D-aspartate (NMDA) glutamate receptor, and inhibit the cyclooxygenase-2 cascade, AST holds promise as a CAM, particularly as a therapeutic agent for nociceptive and pathological pain. Based on the in vivo research findings from our laboratory presented in this review, we have confirmed that carotenoid ASTs possess: (i) an intravenous anesthetic effect on both nociceptive and inflammatory pain comparable to existing analgesics such as ketamine; and (ii) an anti-inflammatory effect on chronic pain with an efficacy almost equivalent to that of the commonly used non-steroidal anti-inflammatory drug (NSAID) celecoxib. Therefore, these findings suggest that, as natural compounds, ASTs contribute to the relief of nociceptive and inflammatory pain, implying their potential for clinical application. Full article

(This article belongs to the Special Issue Marine Carotenoids: Properties, Health Benefits, and Applications)

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15 pages, 1768 KB

Open AccessArticle

Polydeoxyribonucleotide (PDRN) Selectively Promotes Osteoblast Differentiation Without Affecting Osteoclastogenesis

by Younghoon Jeon, Eunjung Heo, Xian Jin, Dong-Kyo Lee, Xiangguo Che, Hyun-Ju Kim, Sung-Hye Byun, Je-Yong Choi, Jeongkyu Choi and Jinyoung Oh

Mar. Drugs 2026, 24(3), 100; https://doi.org/10.3390/md24030100 - 3 Mar 2026

Viewed by 640

Abstract

Developing novel anabolic agents for bone regeneration remains a clinical priority. Polydeoxyribonucleotide (PDRN) exhibits tissue-regenerative properties, but its direct cellular effects on bone remodeling remain unclear. This in vitro study investigated PDRN’s effects on osteoblast (MC3T3-E1) and osteoclast (primary bone marrow-derived macrophages) differentiation. [...] Read more.

Developing novel anabolic agents for bone regeneration remains a clinical priority. Polydeoxyribonucleotide (PDRN) exhibits tissue-regenerative properties, but its direct cellular effects on bone remodeling remain unclear. This in vitro study investigated PDRN’s effects on osteoblast (MC3T3-E1) and osteoclast (primary bone marrow-derived macrophages) differentiation. We evaluated metabolic activity, gene/protein expression, and specific differentiation markers using MTS, qRT-PCR, Western blotting, and functional assays (ALP, Alizarin Red S, TRAP, pit formation). In osteoblasts, PDRN dose-dependently modulated metabolic activity while upregulating the early transcription factor Runx2. PDRN significantly enhanced osteoblast differentiation, evidenced by increased ALP activity, elevated mineralized matrix deposition, and robust upregulation of osteocalcin and Runx2. Conversely, PDRN exhibited no direct effect on osteoclast precursor metabolic activity, differentiation, or resorptive function. These findings support a working hypothesis in which PDRN selectively promotes osteoblast differentiation without directly affecting osteoclastogenesis. While further pharmacological investigations are required to definitively elucidate the specific purinergic receptor mechanisms, our results highlight PDRN as a promising candidate anabolic agent for bone regeneration. Full article

(This article belongs to the Section Biomaterials of Marine Origin)

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33 pages, 3197 KB

Open AccessArticle

Hyaluronic Acid-like Skin Plumping and Radiance Benefits of a Porphyridium Sulfated Exopolysaccharide- and Natural PDRN-Rich Extract

by Fabien Havas, Shlomo Krispin, Moshe Cohen and Joan Attia-Vigneau

Mar. Drugs 2026, 24(3), 99; https://doi.org/10.3390/md24030099 - 1 Mar 2026

Viewed by 844

Abstract

Red microalga Porphyridium cruentum produces a sulfated exopolysaccharide (EPS), which enables its survival in challenging intertidal and spray zones. Extracellular polysaccharide hyaluronic acid (HA) plays important roles in skin hydration, elasticity, and volume. However, with aging, HA decreases and loses effectiveness, reducing skin [...] Read more.

Red microalga Porphyridium cruentum produces a sulfated exopolysaccharide (EPS), which enables its survival in challenging intertidal and spray zones. Extracellular polysaccharide hyaluronic acid (HA) plays important roles in skin hydration, elasticity, and volume. However, with aging, HA decreases and loses effectiveness, reducing skin moisture retention and firmness, and increasing signs of aging. An effective topical alternative to injectable HA replacement remains a largely unmet need. An extract of Porphyridium cultivated in natural sunlight, rich in EPS and polydeoxyribonucleotides (PDRNs), significantly activated the ADORA2A receptor in a CHO model, as well as reduced inflammation and increased collagen and HA production, autophagic flux, and key autophagy gene expression in dermal fibroblast cultures. In a double-blind clinical trial with placebo and HA benchmark controls, the Porphyridium extract delivered significant HA-like skin plumpness, hydration, and radiance benefits, and reduced signs of aging. The extract generally equaled or exceeded the HA benchmark. Its meaningful, swift HA-like activity shows potential for a safe, natural, and arguably more powerful HA-like alternative. Full article

(This article belongs to the Special Issue Marine Natural Products with Anti-Aging Activity, 2nd Edition)

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21 pages, 4632 KB

Open AccessArticle

Antioxidant and Anti-Aging Effects of Porphyra-334 Produced from Saccharomyces cerevisiae in Human Skin Models

by Soeun Park, Saitbyul Park, Nok Hyun Park, Eun-Soo Lee, Kilsun Myoung, Heung-Soo Baek, Jaewoo Jang, Sang-Jip Nam, Jaeyoung Ko and Chang Seok Lee

Mar. Drugs 2026, 24(3), 98; https://doi.org/10.3390/md24030098 - 28 Feb 2026

Viewed by 611

Abstract

Porphyra-334 (PPR-334) is one of the species of mycosporine-like amino acids (MAAs), known as biological UV protection ingredients. In this study, we developed a large-scale purification process to extract PPR-334 from Saccharomyces cerevisiae and confirmed the previously identified efficacy of PPR-334, while also [...] Read more.

Porphyra-334 (PPR-334) is one of the species of mycosporine-like amino acids (MAAs), known as biological UV protection ingredients. In this study, we developed a large-scale purification process to extract PPR-334 from Saccharomyces cerevisiae and confirmed the previously identified efficacy of PPR-334, while also demonstrating its efficacy under UV-independent conditions. PPR-334 scavenged reactivity oxygen species (ROS) and increased catalase (CAT) gene expression in human epidermal keratinocyte cells (HEKa). In both HEKa and normal human dermal fibroblast cells (NHDF), PPR-334 suppressed the gene expression of matrix metalloproteinase-1 (MMP-1). NHDF treated with PPR-334 showed increased collagen expression and proliferation, while advanced glycation end-product (AGE) production was decreased. It was confirmed that the efficacy in vitro was also reproduced in human artificial skin tissue models. Above all, the antioxidant efficacy mechanism of PPR-334 through nuclear factor erythroid 2-related factor 2 (NRF2) and Caspase-9 signals was identified. It was determined that the proliferation efficacy of PPR-334 was due to factors related to the cell cycle. These results demonstrate the anti-aging efficacy of PPR-334 independent of UV irradiation, while enhancing the UV-blocking and antioxidant effects. Thus, we suggest the potential of PPR-334 as a sunscreen agent as well as a dual- or multifunctional material. Full article

(This article belongs to the Special Issue Marine Bioactives for Functional Cosmetics with Health-Promoting Properties)

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23 pages, 11450 KB

Open AccessArticle

Anti-Photoaging Effect of Pinctada martensii Hydrolysates on Ultraviolet B-Irradiated Nude Mice Skin

by Mengfen Wei, Dongcheng Liu, Shiyuan Chang, Lijun You and Oliy Akhmedov

Mar. Drugs 2026, 24(3), 97; https://doi.org/10.3390/md24030097 - 28 Feb 2026

Viewed by 601

Abstract

Pinctada martensii is a marine resource with potential for bioactive peptide development, but its anti-photoaging properties remain underexplored. In this study, Pinctada martensii meat hydrolysates (PME) were prepared by enzymatic hydrolysis, and their anti-photoaging effects were evaluated in an in vivo ultraviolet-B (UVB)-irradiated [...] Read more.

Pinctada martensii is a marine resource with potential for bioactive peptide development, but its anti-photoaging properties remain underexplored. In this study, Pinctada martensii meat hydrolysates (PME) were prepared by enzymatic hydrolysis, and their anti-photoaging effects were evaluated in an in vivo ultraviolet-B (UVB)-irradiated nude mouse model. The results showed that PME markedly ameliorated UVB-induced skin damage. UVB increased epidermal thickness from 21.60 μm in the Control to 47.50 μm in the Model, and PME reduced epidermal thickness to 22.46 μm. Dermal collagen content decreased from 64.58% in the Control to 26.22% in the Model and was restored to 52.75% by PME. UVB upregulated matrix metalloproteinases-1 (MMP-1), MMP-3 and MMP-9 by approximately 2.20-, 1.93- and 3.09-fold relative to the Control, and PME suppressed these matrix metalloproteinases (MMPs) by approximately 61%, 65% and 52%, respectively. Extracellular signal-regulated kinase (ERK) expression increased to 1.41-fold in the Model and was reduced to about 1.05-fold after PME treatment, suggesting inhibition of collagen degradation-related pathways. Untargeted serum metabolomics identified 205 differential metabolites between the Model and the Control, and PME shifted metabolite profiles toward those of the Control. Total short-chain fatty acids (SCFAs) decreased from 868.69 μmol/g in the Control to 301.34 μmol/g in the Model and increased to approximately 562 μmol/g after PME treatment, accompanied by modulation of the gut microbiota including recovery of Lachnospiraceae members, indicating involvement of the gut–skin axis. These findings support the potential of Pinctada martensii meat as a source for developing novel functional foods targeting skin photoaging. Full article

(This article belongs to the Section Marine Pharmacology)

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27 pages, 6120 KB

Open AccessArticle

Characteristics of a Dinophysis cf acuminata Population from a Tidewater Glacier Lagoon in a Temperate Latitude: Applications to Dinophysis Studies

by Patricio A. Díaz, María García-Portela, Gonzalo Álvarez, Francisco Rodríguez, Iván Pérez-Santos, Daniel Varela, Michael Araya, Camila Schwerter, Ángela M. Baldrich, Barbara Cantarero and Beatriz Reguera

Mar. Drugs 2026, 24(3), 96; https://doi.org/10.3390/md24030096 - 28 Feb 2026

Viewed by 1112

Abstract

Dinophysis acuminata, the main agent of diarrhetic shellfish poisoning (DSP) worldwide, shows a high variability in morphology and toxin content between strains from contrasting habitats. Most frequent uncertainties in morphological discrimination are within the “D. acuminata complex”, but confusion with other [...] Read more.

Dinophysis acuminata, the main agent of diarrhetic shellfish poisoning (DSP) worldwide, shows a high variability in morphology and toxin content between strains from contrasting habitats. Most frequent uncertainties in morphological discrimination are within the “D. acuminata complex”, but confusion with other species (e.g., D. norvegica, D. fortii) also occurs. Here we describe a unique PTX2-containing population of Dinophysis cf acuminata observed during opportunistic samplings in San Rafael Lagoon (Chilean Patagonia), the only tidewater glacier lagoon remaining in the glacier with the world’s lowest latitude. Dinophysis acuminata was the only Dinophysis species observed during three seasonal surveys in the well-mixed cold (4–7° C) and brackish (salinity 14–15) waters of the lagoon. Cell densities ranged from 500 cells L⁻¹ (winter) to 2800 cells L⁻¹ (summer). Partial sequences of their ITS rDNA aligned them with D. acuminata strains from Europe and North America, and sequences of their stolen plastids 23S rDNA confirmed ciliates of the Mesodinium rubrum + major complex as their prey and plastid source. All these reasons make this lagoon a highly sensitive area and natural laboratory for climate change-related topics and Dinophysis issues related to (i) the effect of long-term exposure of marine fauna to pectenotoxins and (ii) the adaptations of D. cf acuminata to persist in a unique ecosystem with austral water characteristics located in a warm temperate latitude light regime. Results here add knowledge to the biogeography and habitat ranges of D. acuminata and the problems faced to monitor and provide early warning of its distribution. Full article

(This article belongs to the Special Issue A ‘One-Health Focus’ on Natural Marine Toxins)

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12 pages, 994 KB

Open AccessArticle

Generation of Novel Natural Products by Disrupting Azaphilone Synthesis in Penicillum sclerotiorum E23Y-1A

by Wenjun Chang, Yanhua Yang, Ruijun Duan, Heye Qin, Shiwen Chen and Yanbo Zeng

Mar. Drugs 2026, 24(3), 95; https://doi.org/10.3390/md24030095 - 27 Feb 2026

Viewed by 495

Abstract

Marine-derived filamentous fungi are a rich source of structurally diverse and biologically active natural products. However, many biosynthetic gene clusters (BGCs) in fungi remain silent under standard conditions. In this study, we employed a metabolic shunting strategy to disrupt azaphilone biosynthesis in the [...] Read more.

Marine-derived filamentous fungi are a rich source of structurally diverse and biologically active natural products. However, many biosynthetic gene clusters (BGCs) in fungi remain silent under standard conditions. In this study, we employed a metabolic shunting strategy to disrupt azaphilone biosynthesis in the marine-derived fungus Penicillium sclerotiorum E23Y-1A by deleting the pathway-specific regulator gene A00667. HPLC analysis revealed the emergence of new metabolite peaks in the mutant strain Δ667 compared to the wild type. Subsequent purification yielded seven compounds: the mutant produced two novel meroterpenoids sclerotilins A and B (1 and 2) along with the known steroids ergosta-5,7,22-trien-3β-ol (3) and cerevisterol (4), while the wild type yielded the known steroid (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (5) and two azaphilones geumsanol G (6) and 5-chloro-3-[(1E,3R,4R,5S)-3,4-dihydroxy-3,5-dimethyl-1-hepten-1-yl]-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-(7R,8R,8aS)-6H-2-benzopyran-6-one (7). Bioactivity assays showed that compound 6 exhibited moderate antimicrobial activity against Staphylococcus aureus, and compound 3 displayed moderate cytotoxicity against five human cancer cell lines. These results demonstrate that A00667 is essential for azaphilone biosynthesis and that its disruption leads to the production of structurally distinct natural products, highlighting the potential of pathway engineering to redirect fungal metabolism to yield novel natural products. Full article

(This article belongs to the Section Marine Chemoecology for Drug Discovery)

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11 pages, 1215 KB

Open AccessArticle

Tetrodotoxin Oral Film Attenuates Depression in a Chronic Unpredictable Mild Stress Model in Mice

by Jianlin He, Chao Tang, Siwen Niu, Qingqing Le, Lin Yu and Bihong Hong

Mar. Drugs 2026, 24(3), 94; https://doi.org/10.3390/md24030094 - 26 Feb 2026

Viewed by 458

Abstract

Depression remains a major global health challenge, with a significant proportion of patients failing to respond to conventional antidepressants. This study aimed to evaluate the potential antidepressant effects and toxicological profile of a novel tetrodotoxin (TTX) oral film formulation in a mouse model [...] Read more.

Depression remains a major global health challenge, with a significant proportion of patients failing to respond to conventional antidepressants. This study aimed to evaluate the potential antidepressant effects and toxicological profile of a novel tetrodotoxin (TTX) oral film formulation in a mouse model of chronic unpredictable mild stress (CUMS). Male C57BL/6J mice were subjected to CUMS and treated daily with TTX oral film at doses of 10, 20, and 40 μg/kg, with fluoxetine (18 mg/kg) serving as a positive control. Behavioral assessments, including sucrose preference test, open field test, forced swimming test, elevated plus maze, and novel object recognition, demonstrated that TTX oral film administration alleviated depression- and anxiety-like behaviors and improved cognitive function. Furthermore, TTX oral film treatment restored hippocampal serotonin levels, which were depleted in CUMS mice, and showed no adverse effects on organ indexes after long-term use. Toxicological evaluation through acute toxicity testing revealed an oral LD₅₀ of 919 μg/kg, indicating a substantially improved safety profile compared to pure TTX and a wide therapeutic window. These findings suggest that the TTX oral film possesses significant antidepressant activity with favorable toxicological properties, supporting its potential as a novel and safe treatment for depression. Full article

(This article belongs to the Special Issue A ‘One-Health Focus’ on Natural Marine Toxins)

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30 pages, 4865 KB

Open AccessReview

Bioactive Secondary Metabolites at the Ends of the Earth (2015–2025): Insights into Arctic and Antarctic Aquatic Sources

by Kim-Hoa Phi, Eun Jin Heo, Sunbeom Kwon, Ui Joung Youn and Seulah Lee

Mar. Drugs 2026, 24(3), 93; https://doi.org/10.3390/md24030093 - 26 Feb 2026

Viewed by 1472

Abstract

Marine organisms living in extreme environments such as the Arctic and Antarctic have evolved remarkable adaptation mechanisms to survive harsh conditions, including low temperatures, high salinity, and seasonal fluctuations in light and nutrients. Among these adaptations, unique biochemical pathways have given rise to [...] Read more.

Marine organisms living in extreme environments such as the Arctic and Antarctic have evolved remarkable adaptation mechanisms to survive harsh conditions, including low temperatures, high salinity, and seasonal fluctuations in light and nutrients. Among these adaptations, unique biochemical pathways have given rise to secondary metabolites with unprecedented chemical structures and diverse biological activities. This review focuses on bioactive natural products that have been isolated from polar aquatic organisms between 2015 and 2025. It provides a comprehensive overview of these compounds, highlighting their chemical structures, source organisms, and documented biological activities. By examining recent discoveries from the ends of the Earth, this review underscores the rich chemical diversity of polar marine ecosystems and their continued potential as a source of novel molecules for drug discovery and biotechnology. Full article

(This article belongs to the Special Issue Bioactive Compounds from Challenging Marine Environments)

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21 pages, 7883 KB

Open AccessArticle

Crude Venom from Sea Anemone Macrodactyla doreensis Suppresses Glioblastoma via the p53 Pathway

by Limin Lin, Meiling Huang, Wanting Yang, Ziqiang Hua, Zhen Chen, Panmin He, Kailin Mao, Shuanghuai Cheng, Linlin Ma, Shuaiying Cui, Bo Yi and Bingmiao Gao

Mar. Drugs 2026, 24(3), 92; https://doi.org/10.3390/md24030092 - 26 Feb 2026

Viewed by 566

Abstract

Glioblastoma is a highly invasive primary brain tumor with a poor prognosis, highlighting the need for new therapeutic strategies. Toxins derived from Macrodactyla doreensis have attracted attention for their potential anticancer activity. This study evaluated the anticancer and cytotoxic effects of M. doreensis [...] Read more.

Glioblastoma is a highly invasive primary brain tumor with a poor prognosis, highlighting the need for new therapeutic strategies. Toxins derived from Macrodactyla doreensis have attracted attention for their potential anticancer activity. This study evaluated the anticancer and cytotoxic effects of M. doreensis crude venom on two commonly used glioblastoma cell lines (U251 and LN229), which mirror the phenotype of primary tumors. Cell viability and proliferation were assessed using the CCK-8 assay and colony formation assay, while cell migration and invasion capabilities were detected via wound healing assay and Transwell assay. Annexin V/PI staining and PI-based cell cycle analysis indicated that the crude venom significantly induced cell apoptosis and caused S-phase arrest. Proteomic analysis combined with GO and KEGG enrichment analyses as well as bioinformatics approaches showed that M. doreensis crude venom inhibits glioblastoma cell proliferation by downregulating the expression of CDK2, RRM2, and CHEK1, thereby hindering cell cycle progression and regulating the p53 signaling pathway. Notably, the downregulation of these key glioblastoma-related target genes was validated by qPCR. In addition, network pharmacology analysis indicated that several peptide families present in the sea anemone crude venom, including ShK peptides, inhibitor cystine knot (ICK) peptides, and EGF-like peptides, exhibit notable antitumor potential. Combined with AlphaFold2-based structural modeling and molecular docking, these analyses further elucidated the potential molecular mechanisms underlying their interactions with key targets, such as MD-381 with RRM2, MD-322 with CDK2, and MD-429 with CHEK1. Collectively, these findings highlight the therapeutic potential of M. doreensis crude venom and lay a foundation for the subsequent isolation of novel peptides and their further development in glioblastoma treatment. Full article

(This article belongs to the Special Issue Marine Toxins: Characterization, Detection, Classification and Potential Therapeutics)

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Mar. Drugs, Volume 24, Issue 3 (March 2026) – 34 articles

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