Marine Drugs

22 pages, 1042 KB

Open AccessReview

Sulfated Polysaccharides in Cancer Therapy: A Focus on Algal-Derived Bioactive

by N. M. Liyanage, D. S. Dissanayake, Yiqiao Li, Kyung Yuk Ko, D. P. Nagahawatta and You-Jin Jeon

Mar. Drugs 2026, 24(4), 131; https://doi.org/10.3390/md24040131 - 31 Mar 2026

Abstract

Sulfated polysaccharides (SPs), biologically active macromolecules from marine and terrestrial organisms, hold significant potential in revolutionizing cancer therapy. Characterized by their unique sulfate ester groups and structural diversity, SPs exhibit a broad spectrum of bioactivities, including immunomodulation, apoptosis induction, metastasis suppression, and angiogenesis [...] Read more.

Sulfated polysaccharides (SPs), biologically active macromolecules from marine and terrestrial organisms, hold significant potential in revolutionizing cancer therapy. Characterized by their unique sulfate ester groups and structural diversity, SPs exhibit a broad spectrum of bioactivities, including immunomodulation, apoptosis induction, metastasis suppression, and angiogenesis inhibition. Prominent SPs, such as fucoidan from brown algae and carrageenan from red algae, have shown remarkable anticancer properties, either as standalone agents or in synergy with conventional therapies like chemotherapy and radiotherapy. Their mechanisms of action involve targeting critical pathways such as NF-kB, VEGF, and PI3K/Akt, disrupting cancer cell proliferation, invasion, and tumor microenvironment dynamics. SPs also enhance immune system responses, reduce chemotherapy-induced side effects, and exhibit antioxidant properties, making them versatile candidates in cancer treatment. Innovations like SP-based nanoparticles are addressing bioavailability and drug delivery challenges, providing targeted and sustained therapeutic effects while minimizing off-target toxicity. Despite their promise, challenges such as structural complexity, scalability, and clinical validation hinder their widespread adoption. This review provides a comprehensive analysis of SPs’ therapeutic potential, mechanisms, and emerging applications in oncology. It emphasizes the need for advanced extraction, characterization techniques, and clinical research to unlock their full potential, paving the way for novel, efficient, and safer cancer therapies. Full article

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17 pages, 2745 KB

Open AccessArticle

Phaseolorin J Alleviates Cellular Inflammation and Oxidative Stress by Inhibiting NLRP3 Inflammasome Expression via the Nrf2/HO-1 Pathway

by Yuanjie Chen, Ting Feng, Xiaojing Li, Jing Xu and Juren Cen

Mar. Drugs 2026, 24(4), 130; https://doi.org/10.3390/md24040130 - 31 Mar 2026

Abstract

Phaseolorin J (TT-55), a chromone compound isolated and purified from the fermentation products of Phomopsis asparagi DHS-48, is an endophytic fungus obtained from mangrove forests. Preliminary experimental studies have revealed its potent antioxidant and anti-inflammatory activities, though its mechanism of action remains unclear. [...] Read more.

Phaseolorin J (TT-55), a chromone compound isolated and purified from the fermentation products of Phomopsis asparagi DHS-48, is an endophytic fungus obtained from mangrove forests. Preliminary experimental studies have revealed its potent antioxidant and anti-inflammatory activities, though its mechanism of action remains unclear. In this study, we aimed to investigate the molecular mechanisms underlying the antioxidant and anti-inflammatory effects of TT-55, following initial evidence of its potency, by employing an LPS-induced RAW264.7 macrophage model in vitro. The results revealed that in the LPS-induced inflammatory model of RAW264.7 cells, the TT-55 dose dependently inhibited the expression of LPS-induced inflammatory cytokines (TNF-α, IL-18, IL-1β, IL-6) and the production of oxidative stress markers (reactive oxygen species, SOD, MDA). Following combined treatment with the Nrf2 pathway inhibitor ML385 and TT-55, the inhibitory effects of TT-55 on inflammatory cytokines and oxidative stress markers were reversed by ML385. Meanwhile, ML385 also attenuated the ability of TT-55 to suppress LPS-induced upregulation of NLRP3 inflammasome-related genes. In conclusion, TT-55 may exert its antioxidant and anti-inflammatory effects by activating the Nrf2/HO-1 signaling pathway and suppressing the upregulation of NLRP3 inflammasome-related genes. Full article

(This article belongs to the Special Issue Marine Bioactive Compound Discovery Through OSMAC Approach—2nd Edition)

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26 pages, 1295 KB

Open AccessReview

Recent Advance in Marine Polysaccharides: Structure, Anti-Inflammatory Mechanisms, and Functional Applications

by Yuchen Wang, Jingyi Luo, Chao Xu, Dongyu Hu, Yimeng Li, Yanzuo Ye, Jun Yang, Xianxiang Chen, Chuan Li and Kexue Zhu

Mar. Drugs 2026, 24(4), 129; https://doi.org/10.3390/md24040129 - 31 Mar 2026

Abstract

Inflammation is pivotal to the pathogenesis of chronic disorders, including diabetes and cardiovascular disorders. Conventional pharmaceuticals used in the treatment of inflammation and related diseases face several challenges. In recent years, polysaccharides isolated from marine organisms have attracted extensive research attention due to [...] Read more.

Inflammation is pivotal to the pathogenesis of chronic disorders, including diabetes and cardiovascular disorders. Conventional pharmaceuticals used in the treatment of inflammation and related diseases face several challenges. In recent years, polysaccharides isolated from marine organisms have attracted extensive research attention due to their good safety profile, easy availability, and powerful anti-inflammatory properties. However, there is still a lack of systematic elucidation of their anti-inflammatory mechanisms and functional effects. In this review, the sources and structural characteristics of marine polysaccharides were reviewed. Moreover, the anti-inflammatory mechanisms of marine polysaccharides and their advanced applications were discussed. Finally, the current challenges of marine polysaccharides in anti-inflammatory research and food industry applications, as well as future research directions, were proposed. This review deepens the understanding of the anti-inflammatory effects of marine polysaccharides and provides feasible guidance for the development and clinical application of novel anti-inflammatory drugs. Full article

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

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12 pages, 982 KB

Open AccessArticle

Chemical Diversity and Antitumor Metabolites from Soft Coral-Derived Fungus Aspergillus sclerotiorum SCSIO 41031 via OSMAC Strategy

by Juan Gao, Jieyi Long, Xiaoyan Pang, Xuefeng Zhou, Yonghong Liu and Bin Yang

Mar. Drugs 2026, 24(4), 128; https://doi.org/10.3390/md24040128 - 31 Mar 2026

Abstract

Microorganisms provide critical lead compounds for drug development, yet most biosynthetic gene clusters remain silent under standard culture conditions. The OSMAC strategy activates these clusters by adjusting cultivation parameters, thereby enabling the discovery of novel compounds from a single strain. Here, we applied [...] Read more.

Microorganisms provide critical lead compounds for drug development, yet most biosynthetic gene clusters remain silent under standard culture conditions. The OSMAC strategy activates these clusters by adjusting cultivation parameters, thereby enabling the discovery of novel compounds from a single strain. Here, we applied OSMAC to explore the metabolic potential of the soft coral-derived fungus Aspergillus sclerotiorum SCSIO 41031. Three different culture media were employed for the large-scale fermentation process. After isolation by chromatography, the compounds were structurally characterized using NMR, MS, and X-ray single-crystal diffraction, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. In total, three new compounds, named 6,6′-diacetyl-1,1′-dihydroxy-3,3′-dimethoxydibenzyl ether (1), esterwortmannolol (17) and pestalpolyol I (20), along with 19 known compounds (2–16, 18–19 and 21–22) were obtained. This study validates the efficacy of the OSMAC strategy and underscores that A. sclerotiorum SCSIO 41031 serves as a valuable resource for producing structurally diverse natural products with potent biological activities. Full article

(This article belongs to the Special Issue Marine Bioactive Compound Discovery Through OSMAC Approach—2nd Edition)

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15 pages, 5502 KB

Open AccessArticle

Preparation of Alginate Oligosaccharides by Autoclaving Pretreatment Combined with Enzymatic Method

by Feiyu Niu, Ziqiang Gu, Zihan Yu, Zhi Bao, Jichao Li, Peng Yang, Dongyu Li, Haijin Mou and Changliang Zhu

Mar. Drugs 2026, 24(4), 127; https://doi.org/10.3390/md24040127 - 30 Mar 2026

Abstract

The enzymatic method is the primary focus for alginate oligosaccharide (AOS) production. However, the high viscosity of sodium alginate (SA) substrate often limits enzymatic efficiency. Pretreatment strategies aimed at reducing SA viscosity offer a promising and innovative solution to enhance process efficiency. This [...] Read more.

The enzymatic method is the primary focus for alginate oligosaccharide (AOS) production. However, the high viscosity of sodium alginate (SA) substrate often limits enzymatic efficiency. Pretreatment strategies aimed at reducing SA viscosity offer a promising and innovative solution to enhance process efficiency. This study compared the effects of three pretreatment methods—high-pressure vapor (HP-v), high-pressure solution (HP-s), and atmospheric-pressure air (AP-a)—on the physicochemical properties of SA. These pretreatments reduced SA viscosity and induced visible color changes in the order HP-v > HP-s > AP-a. Additionally, the effects of high-pressure treatments on molecular weight, M/G ratio, and chemical structure of SA were analyzed, confirming the feasibility of pretreatment-assisted enzymolysis. Molecular weight distribution and ESI-MS analysis of AOS after enzymolysis demonstrated that brief HP-v treatment maximizes the catalytic potential of alginate lyase, facilitating efficient AOS production without altering its structural characteristics. Full article

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

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24 pages, 7162 KB

Open AccessArticle

Orally Administered Rhamnan Sulfate from Monostroma nitidum Significantly Inhibits Melanoma Metastasis in Lungs and Aorta of Mice Implanted with B16 Cells

by Keiichi Hiramoto, Masashi Imai, Masahiro Terasawa and Koji Suzuki

Mar. Drugs 2026, 24(4), 126; https://doi.org/10.3390/md24040126 - 29 Mar 2026

Abstract

Tumor metastasis is closely associated with coagulation and inflammation, particularly via thrombin–PAR1 signaling. However, the potential of natural polysaccharides such as rhamnan sulfate (RS) to modulate these pathways and suppress metastasis remains unclear. We aimed to investigate the effects of orally administered RS [...] Read more.

Tumor metastasis is closely associated with coagulation and inflammation, particularly via thrombin–PAR1 signaling. However, the potential of natural polysaccharides such as rhamnan sulfate (RS) to modulate these pathways and suppress metastasis remains unclear. We aimed to investigate the effects of orally administered RS derived from Monostroma nitidum on melanoma metastasis and its underlying mechanisms. Male C57BL/6J mice were orally administered water or RS daily. On day 8, saline or B16 melanoma cells were injected intravenously. Mice were treated for 21 days and divided into four groups (control, RS-only, M + W, and M + RS; n = 5/group). Metastasis and related molecular factors were analyzed in plasma, lung, and aortic tissues. Significant lung and aortic metastases were observed in the M + W group but were markedly suppressed in the M + RS group. RS reduced the expression of inflammatory factors (e.g., IL-6, PAR1), proteases, leukocyte activation markers, complement factors, angiogenic factors, and EMT-related factors. Conversely, thrombin, thrombomodulin, plasmin, TAFIa, and tight junction proteins were increased in RS-treated mice. RS suppresses melanoma metastasis by modulating thrombin–PAR1-mediated inflammation and associated pathways. These findings suggest RS as a potential therapeutic agent, although further mechanistic and clinical studies are required. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents—6th Edition)

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16 pages, 6676 KB

Open AccessArticle

Anti-Neuroinflammatory Naphtho-γ-Pyrones from a Deep-Sea-Derived Fungus Aspergillus niger 3A00562

by Zi-Han Xu, Zheng-Biao Zou, Chun-Xiu Wang, Chen Li, Xian-Wen Yang and Jun-Song Wang

Mar. Drugs 2026, 24(4), 125; https://doi.org/10.3390/md24040125 - 27 Mar 2026

Abstract

Inhibition of inflammation and oxidative stress is increasingly recognized as a promising therapeutic strategy for neurodegenerative diseases. In this study, we isolated two new dimeric naphtho-γ-pyrone (aS)-fonsecinones B and D (1 and 2) and 14 known compounds [...] Read more.

Inhibition of inflammation and oxidative stress is increasingly recognized as a promising therapeutic strategy for neurodegenerative diseases. In this study, we isolated two new dimeric naphtho-γ-pyrone (aS)-fonsecinones B and D (1 and 2) and 14 known compounds (3–16) from the deep-sea-derived fungus Aspergillus niger 3A00562. Their structures were unambiguously determined through integrated physicochemical and spectroscopic analyses. Screening for neuroinflammatory inhibitors using a BV2 microglial cell model identified TMC 256 A1 (10) as the most potent candidate. Compound 10 significantly suppressed LPS-induced inflammation in BV2 cells without cytotoxicity. It concurrently inhibited LPS-triggered ROS overproduction and neutrophilic infiltration in zebrafish. Subsequent proteomics revealed that 10 targets NOS2 to modulate Alzheimer’s disease (AD)-associated pathways and the KEAP1-NRF2 axis. Molecular docking and dynamics simulations demonstrated that 10 occupies the NOS2 heme-binding pocket, thereby preventing dimerization and inhibiting enzymatic activity. Finally, 10 ameliorated locomotor deficits in an AD zebrafish model. Collectively, these findings highlight compound 10 as a candidate compound for preventing inflammatory and oxidative stress damage during treatment of neurodegenerative diseases, particularly AD. Full article

(This article belongs to the Special Issue The Deep Sea as a Treasure Trove: Discovery, Characterization and Applications of Microorganisms and Their Metabolites)

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34 pages, 7037 KB

Open AccessArticle

On the Design of Chlorella vulgaris Composition for Potential Food Uses via Manipulation of Cultivation Conditions

by Ana S. Pinto, Joana Oliveira, Ana F. Esteves, Susana Casal, Gustavo Mil-Homens, Francisco X. Malcata, José C. M. Pires and Tânia G. Tavares

Mar. Drugs 2026, 24(4), 124; https://doi.org/10.3390/md24040124 - 26 Mar 2026

Abstract

Interest in microalgae-based technologies has emerged in recent years as a response to environmental challenges and the global food crisis, for providing alternative and sustainable food products. This study used temperature variations between 18 and 32 °C and nitrogen-to-phosphorus (N:P) ratios between 1.9 [...] Read more.

Interest in microalgae-based technologies has emerged in recent years as a response to environmental challenges and the global food crisis, for providing alternative and sustainable food products. This study used temperature variations between 18 and 32 °C and nitrogen-to-phosphorus (N:P) ratios between 1.9 and 42.6 to model and optimize growth and composition of Chlorella vulgaris, a nutritionally interesting species. Lower temperatures appear ideal for this strain. An increase in average biomass productivity was observed with decreasing temperature, leading to a maximum of 122.27 mg_dw L⁻¹ d⁻¹ at 18 °C on the fourth day of cultivation. The maximum productivities for total proteins, fatty acids, carbohydrates, and pigments were, respectively, 26.9 mg L⁻¹ d⁻¹, 26.4 mg L⁻¹ d⁻¹, 16.0 mg L⁻¹ d⁻¹, and 2.41 mg L⁻¹ d⁻¹, all referring to 18 °C. The fatty acid, carotenoid, and amino acid profiles were also ascertained; several indicators suggested that cultivation of these microalgae under the aforementioned optimal conditions holds potential for the food industry. The high proportion of polyunsaturated fatty acids—including two essential fatty acids; the high production of lutein, and the presence of several essential amino acids are among the favorable indicators. Overall, the information generated by this study is helpful to support future pilot studies aimed at the commercial production of microalgae-derived products. Full article

(This article belongs to the Special Issue Applications of Marine Microalgal Biotechnology)

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19 pages, 4509 KB

Open AccessArticle

Molecular Characterization and Mechanistic Insights of a Thermostable Neoagarobiose Hydrolase Aga2457 from Alteromonas sp.

by Jiang Li, Xinning Pan, Long Chen, Qian Zhang, Zhiyan Wang, Dewi Seswita Zilda and Zhou Zheng

Mar. Drugs 2026, 24(4), 123; https://doi.org/10.3390/md24040123 - 25 Mar 2026

Abstract

The enzymatic valorization of agarose, a major polysaccharide in red algae, is critical for its application in the food, pharmaceutical, and biotechnology industries. In this study, a gene encoding a thermostable α-neoagarobiose hydrolase, aga2457, was cloned from an epiphytic bacterium associated with [...] Read more.

The enzymatic valorization of agarose, a major polysaccharide in red algae, is critical for its application in the food, pharmaceutical, and biotechnology industries. In this study, a gene encoding a thermostable α-neoagarobiose hydrolase, aga2457, was cloned from an epiphytic bacterium associated with Indonesian macroalgae. Unlike typical mesophilic GH117 enzymes, recombinant Aga2457 displayed a higher optimal temperature at 50 °C and retained 55% activity after 12 days of incubation at 50 °C. The enzyme specifically hydrolyzes neoagarobiose into D-galactose and 3,6-anhydro-L-galactose, thereby facilitating the complete depolymerization of agarose. Combined molecular dynamics (MD) simulations and site-directed mutagenesis revealed that residues P253, N256, and Q285 are pivotal for substrate recognition and active site stability. These findings highlight Aga2457 as a robust biocatalyst for industrial agar processing and provide structural insights for the rational design of thermostable agarolytic enzymes. Full article

(This article belongs to the Special Issue Marine-Derived Polysaccharide-Degrading Enzyme)

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16 pages, 1097 KB

Open AccessCommunication

In Vitro Validation of Size-Dependent Antiviral Activity of Phaeodactylum tricornutum-Derived Peptide Fractions Against SARS-CoV-2

by David Mauricio Cañedo-Figueroa, Blanca Azucena Márquez-Reyna, Alan Orlando Santos-Mena, Daniela Nahomi Calderón-Sandate, Flor Itzel Lira-Hernández, Julio E. Castañeda-Delgado, Ana Cristina García-Herrera, Rosa María del Ángel, Moisés León-Juárez, Marco Antonio Valdez-Flores, Gabriela López-Angulo, Claudia Desireé Norzagaray-Valenzuela, Loranda Calderón-Zamora, Evelin Cervantes-Bobadilla, Juan Fidel Osuna-Ramos and Luis Adrián De Jesús-González

Mar. Drugs 2026, 24(4), 122; https://doi.org/10.3390/md24040122 - 25 Mar 2026

Abstract

The continuous emergence of SARS-CoV-2 variants highlights the need for novel antiviral agents with favorable safety profiles. Marine microalgae constitute a valuable source of bioactive compounds, including antiviral peptides. Building on previous in silico identification of peptides derived from the marine microalga Phaeodactylum [...] Read more.

The continuous emergence of SARS-CoV-2 variants highlights the need for novel antiviral agents with favorable safety profiles. Marine microalgae constitute a valuable source of bioactive compounds, including antiviral peptides. Building on previous in silico identification of peptides derived from the marine microalga Phaeodactylum tricornutum with predicted activity against SARS-CoV-2, this study evaluated the antiviral capacity of peptide fractions generated by enzymatic hydrolysis and separated by molecular weight (10–30, 5–10, 3–5, and <3 kDa) in human alveolar epithelial A549 cells infected with the SARS-CoV-2. Cytotoxicity analyses, assessed using MTT and resazurin assays, revealed a moderate, concentration-dependent reduction in metabolic activity while maintaining overall cell viability within an acceptable range for antiviral evaluation, with higher-molecular-weight fractions (10–30 and 5–10 kDa) displaying the most stable profiles. Antiviral activity was assessed by flow cytometry following post-infection treatment. Lower-molecular-weight fractions (3–5 and <3 kDa) showed early reductions in infection at low concentrations but exhibited variable responses. In contrast, the 10–30 and 5–10 kDa fractions showed more robust, dose-dependent inhibition at medium and high concentrations, reducing infection levels to levels close to those observed in uninfected controls. Comparative analysis with the reference antiviral drug lopinavir demonstrated that peptide fractions exhibit lower cytotoxicity while retaining antiviral activity under equivalent experimental conditions. Overall, these results indicate that antiviral efficacy is strongly influenced by peptide molecular weight and consistency of response. This work provides experimental in vitro validation of P. tricornutum–derived peptide fractions as marine antiviral candidates and supports the integration of in silico and functional approaches for marine drug discovery. Full article

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

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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

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

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

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

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

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

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

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

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

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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